Prevalence and predictors of pulmonary arterial hypertension and right ventricular dysfunction in HIV-infected adolescents in Nigeria: a cross-sectional study

Prevalence and predictors of pulmonary arterial hypertension and right ventricular dysfunction in HIV-infected adolescents in Nigeria: a cross-sectional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence and predictors of pulmonary arterial hypertension and right ventricular dysfunction in HIV-infected adolescents in Nigeria: a cross-sectional study Cressida Kfunsei Amichoh, Motunrayo Oluwabukola Adekunle, Cecilia Abimbola Mabogunje, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4966002/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Right ventricular dysfunction (RV dysfunction) is a major cause of morbidity and mortality in HIV-associated pulmonary arterial hypertension (PAH). The clinical manifestations are non-specific and similar to the cardiorespiratory symptoms of comorbid opportunistic infections in HIV-infected individuals, thus leading to misdiagnosis. However, there is a paucity of data on the burden of HIV-associated PAH and RV dysfunction in Nigeria and sub-Saharan Africa. Hence, we evaluated the prevalence and predictors of PAH and RV dysfunction among adolescents living with HIV and uninfected controls. Methods This was an analytical, cross-sectional study of 90 HIV-infected adolescents and 90 HIV-negative controls aged 10–19 years. Using transthoracic echocardiography, pulmonary artery pressure was estimated using pulmonary artery systolic pressure (PASP), and RV function was estimated using tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RV FAC). Pulmonary artery hypertension was defined as a PASP ≥ 30 mmHg and RV dysfunction with a TAPSE of < 1.6 cm or RV FAC < 34%. Results The mean ages of the HIV-positive adolescents and controls were 14.81 ± 2.9 and 14.52 ± 2.8 years, respectively (p = 0.497). The prevalence of PAH was significantly greater in HIV-positive adolescents than in controls (7.8% vs 1.1%, p = 0.030), as was the prevalence of RV dysfunction (8.9% vs 1.1%, p = 0.017). PAH was independently associated with decreasing PCV (adjusted OR [95% CI] = 0.62 [0.29–0.91], p < 0.001), whereas RV dysfunction was independently associated with delayed age at diagnosis (age 10 years and above) (adjusted OR [95% CI] = 3.85 [1.34–7.01], p = 0.043). Conclusion Pulmonary artery hypertension and RV dysfunction were significantly more common among HIV-positive adolescents than among HIV-negative controls. Strengthening early diagnosis, prompt treatment with optimization of the hematologic profile and the integration of periodic echocardiography into routine HIV care are advocated. Clinical trial number: Not applicable PAH RV dysfunction HIV adolescents children sub-Saharan Africa echocardiography Figures Figure 1 Introduction Globally, highly active antiretroviral therapy (HAART) has changed HIV infection from an acute, often fatal, illness to a lifelong manageable chronic disease. 1 Consequently, HIV-infected children now survive into adolescence and adulthood but at the expense of an increased risk of chronic non-communicable diseases (NCDs), including those of the cardiovascular system, which are mediated via direct viral and indirect mechanisms. 2 These HIV-associated cardiovascular diseases (HIV-CVDs) are usually subclinical and, thus, often unrecognized, especially in early stages. 2 , 3 HIV-CVD ranges from subtle abnormalities in cardiac size and function to more severe disorders, such as dilated cardiomyopathy, myocarditis, coronary artery disease, and pulmonary artery hypertension (PAH). 4 – 9 Notably, PAH is a progressive and fatal disorder culminating in RV dysfunction, which is, in turn, a major determinant of outcome and survival among HIV-infected individuals. 10 Unfortunately, the symptoms of PAH and RV dysfunction are non-specific and often similar to the cardiorespiratory symptoms of HIV-related opportunistic infections. 3 Several echocardiographic parameters can be used to non-invasively assess RV function; notably, the tricuspid annular plane systolic excursion (TAPSE) can be used to assess global RV function. 11 Additionally, the RV fractional area change (RV FAC), which can detect early RV changes, even when the TAPSE is normal. 12 There is a paucity of published reports on the prevalence of PAH and RV dysfunction among HIV-infected children and adolescents globally, especially in Africa. 13 – 17 Most reports are from the adult population, with a global prevalence of 0.5–38%. 17–21 However, the findings in HIV-infected adults may not apply to adolescents, for example, because the latter and their organs are still growing. Furthermore, whereas much is known about HIV-associated left ventricular (LV) abnormalities, 3 , 5 – 8 considerably less is known about RV dysfunction in HIV-infected children and adolescents, despite being a possible indicator of the presence of PAH and a determinant of HIV-associated cardiac morbidity and mortality. 22 Thus, the early detection and management of PAH and its associated RV dysfunction among adolescents living with HIV (ALHIV) is important for halting or slowing progression to right heart failure and death. This may require the integration of periodic echocardiographic screening into routine HIV care, informed by relevant epidemiologic data. Additionally, the knowledge of predictors of PAH and RV dysfunction may guide targeted preventive interventions, as well as identifying subsets of ALHIV who may be prioritized for such screening where resources are limited. We thus aimed to determine the prevalence and predictors of PAH and RV dysfunction among HIV-infected adolescents in an HIV Clinic in Lagos, Nigeria, using echocardiographically measured pulmonary artery systolic pressure (PASP), TAPSE, and RV FAC. Methods Study design and population We conducted this analytical cross-sectional study of HIV-infected children aged 10–19 years, with sex- and age-matched HIV-negative controls, over four months (April to July 2023) at the Adolescents’ HIV Clinic of Massey Street Children’s Hospital (MSCH), a 102-bed government-owned Pediatric hospital in Lagos Island. The MSCH serves as a referral center for primary and secondary health facilities across Lagos State and neighboring states. Its services include the care of HIV-infected children and adolescents, as well as general and specialist pediatric services such as cardiology services. Sample selection and sampling technique We consecutively recruited HIV-infected adolescents aged 10–19 years who had been attending the HIV outpatient clinic and were on HAART for at least six months. These adolescents had been previously confirmed to be HIV positive at enrollment in the Pediatric HIV Program on the basis of extant National Guidelines for HIV Management. 23 We excluded those with current or recent acute illness in the preceding two weeks; a history and/or physical features suggestive of sickle cell anemia; congenital or acquired heart diseases; connective tissue diseases; pulmonary diseases; chronic renal disease; schistosomiasis; and drug therapy with potential cardiovascular effects. We also recruited age- and sex-matched healthy HIV-negative adolescents (confirmed negative with a rapid test according to National HIV guidelines 23 ) with these exclusion criteria from general outpatient clinics. Sample size We determined the sample size using the following formula for comparing two proportions: n= ([Z α + Z β ]2[p 1 q 1 + p 2 q 2 )/A 2 , where n = minimum sample size per group; Z α = standard normal deviate (SND) at 95% confidence interval (CI) = 1.96; Z β = SND at the power of (1-β) = 90%., i.e., 1.24; p 1 = proportion of PAH among the HIV-positive group (7.0%) 24 [= 0.07] reported among Zimbabwean HIV-infected adolescents); p 2 = proportion of PAH among the HIV-negative control group (2%) 25 [= 0.02] reported among the Nigerian general population); A = minimum assumed significant difference between groups set at = 0.1; n = 86.73, approximately 90 per group, totaling 180. The participants were distributed equally across sex and age subgroups (10–13 years, 14–16 years, and 17–19 years, representing early, middle and late adolescents, respectively), with 30 participants in each subgroup. Data collection Sociodemographic and clinical data Sociodemographic (age, sex, and socioeconomic class) and clinical data (age at diagnosis, age at commencement of ART, type and duration of ART, and stage of HIV disease) were obtained from the parents and medical records and recorded in self-designed data collection forms. Socioeconomic class was derived with a scale for Nigerian children and was graded as low, medium or high. Screening examination We conducted brief physical examinations to check for pallor, cyanosis, finger-clubbing, and standardized anthropometry (weight in kilograms) to the nearest 0.1 kg using a weight scale (Seca®, Germany) and height to the nearest 0.1 cm using a stadiometer (ADE®, Germany). Echocardiography We performed transthoracic echocardiography using an M5 Mobile Digital Color Doppler Ultrasound System (MINDRAY, China) with a 2.0– to 4.0-MHz phased array transducer for 2-dimensional, M-mode, color flow mapping and Doppler studies. According to the American Society of Echocardiography (ASE), 26 PAH was defined as a pulmonary artery systolic pressure ( PASP ) ≥ 30 mmHg , with a PASP equivalent to the RV systolic pressure derived from the tricuspid regurgitant velocity (TRV) via the simplified Bernoulli equation, 4 × TRV. 27 We assessed RV systolic function with the TAPSE and RVFAC. Tricuspid annular plane systolic excursion was obtained in the apical 4-chamber view via the M-mode cursor placed across the lateral tricuspid annulus, and the total excursion was measured from the base of the heart to the apex at the end of systole. RV FAC was obtained from the apical 4-chamber view by tracing the RV endocardium both in systole and diastole from the annulus, along the free wall to the apex, and then to the annulus along the interventricular septum. It was calculated as the difference in the end-diastolic area and the end-systolic area divided by the end-diastolic area. 26 We defined RV dysfunction as a TAPSE of < 1.6 cm or an RV FAC of < 34% . 26 Hematological assays We obtained 2 ml of venous blood from each participant into an EDTA bottle for estimation of the packed cell volume (PCV). We also assayed each participant’s CD4 count via a point-of-care device (VISITEC CD4 Advanced Disease Test Kit, Omega Diagnostics Ltd., Scotland), expressed semiquantitatively as < 200 and ≥ 200 cells/µL. Data analysis We analyzed the data with SPSS version 26 (IBM, Inc., USA). Associations between categorical variables were assessed via the chi-square test or Fisher’s exact test. Comparisons of continuous variables between two groups were carried out via Student’s t test or the Mann‒Whitney U test if the data were skewed. Binary logistic regression was used to determine independent predictors of PAH and RV dysfunction. Statistical significance was set at a p value less than 0.05 at the 95% confidence interval (CI). Results Overall, we recruited 215 participants. Of these, 35 were excluded because of recent or current tuberculosis. Sociodemographic and clinical characteristics of HIV-infected adolescents and controls Table 1 shows the socioclinical characteristics of the 180 adolescents (90 HIV-positive, 90 HIV-negative). There were more orphaned children in the HIV-infected group than in their HIV-negative counterparts (38.8% vs 4.4%, p < 0.001). Compared with controls, HIV-infected adolescents also had lower diastolic blood pressure (65.6 vs 68.8 mmHg); other variables, such as anthropometrics, pulse, systolic blood pressure, oxygen saturation, respiratory rate and packed cell volume, were similar between them. Table 1: Socioclinical and right ventricular characteristics of the participants HIV-positive (n = 90) n (%) HIV-negative (n = 90) n (%) χ 2 P -value Age group (Years) 10 – 13 14-16 17-19 Mean ± SD 30 (33.3) 30 (33.3) 30 (33.3) 14.81 ± 2.9 30 (33.3) 30 (33.3) 30 (33.3) 14.52 ± 2.8 0.000 0.681 ** 1.000 0.497 Sex Male Female 45 (50.0) 45 (50.0) 45 (50.0) 45 (50.0) 0.000 1.000 Social class Upper Middle Lower 4 (4.4) 11 (12.2) 75 (83.3) 9 (10.0) 17 (18.9) 64 (71.1) 4.079 0.130 Orphan status Both parents alive Only one alive Both dead 55 (61.1) 31 (34.4) 4 (4.4) 86 (95.6) 4 (4.4) 0 (0.0) 31.644 <0.001* Weight (kg) 44.94 ± 13.9 44.76 ± 10.9 0.101 0.919 Height (m) 1.54 ± 0.1 1.57 ± 0.1 -1.508 0.133 BMI (weight/m 2 ) 18.61 ± 3.7 18.30 ± 3.6 0.564 0.574 BSA (m 2 ) 1.39 ± 0.2 1.41 ± 0.2 -0.564 0.574 Pulse rate (beat/mins) 82.74 ± 14.4 83.38 ± 13.2 -0.307 0.759 SBP (mmHg) 107.68 ± 9.2 109.82 ± 10.3 -1.554 0.122 DBP (mmHg) 65.61 ± 6.9 68.82 ± 10.3 -2.535 0.012* Oxygen saturation (%) 97.75 ± 1.0 97.80 ± 0.9 -0.327 0.744 Respiratory rate (cpm) 17.09 ± 1.9 17.24 ± 1.3 -0.637 0.525 PCV (%) 36.72 ± 5.1 37.01 ± 5.3 0.910 0.074 PASP, mmHg *** 15.00 (11.9, 18.5) 12.74 (9.7, 16.3) 2.812 0.005* TAPSE, cm RV FAC, % 2.23 ± 0.4 54.53 ± 13.0 2.16 ± 0.3 52.09 ± 12.8 1.419 1.268 0.158 0.207 χ 2 = chi square test; *significant, **Independent Student’s t test, *** Mann‒Whitney U test HIV = Human immunodeficiency virus; kg = Kilogram, BSA = Body surface area, BMI = Body mass index; SBP = Systolic blood pressure; DBP = Diastolic blood pressure; mmHg = Millimeter of mercury; cpm = cycles per minute; PCV = Packed cell volume, PASP = Pulmonary artery systolic pressure, TAPSE = Tricuspid annular plane systolic excursion, cm = Centimeter, RV FAC = Right ventricular fractional area change. Clinical and immunological profiles of HIV-infected adolescents Approximately half of the participants (47.8%) had early-stage HIV disease (WHO clinical stages I and II) (Table 2 ). Approximately one-quarter (25.6%) commenced HAART after 10 years of age. Most (90.0%) were exposed to a nucleoside-based ART regimen. Most of them were asymptomatic at recruitment (95.6%, n = 86). Table 2: Clinical and immunological profiles of the HIV-positive participants Variable Frequency (n=90) Percentage WHO HIV clinical stage I-II III-IV 47 43 52.2 47.8 Current ART regimen Nucleoside exposed Protease inhibitor exposed Symptoms and signs 81 9 90.0 10.0 Asymptomatic Symptomatic* 86 4 95.6 4.4 Age at the commencement of ART (years) 120 Median (Q1 - Q3) 24 21 45 120.00 (58.3-172.5) 26.7 23.3 50.0 CD4 count (cells/µL) <200 ≥200 35 55 38.9 61.1 Viral load (copies/ml) <1000 ≥1000 72 18 80.0 20.0 Commencement of ART** Before 2015 After 2015 56 34 62.2 37.8 HIV = Human Immunodeficiency Virus, WHO = World Health Organization, ART = Antiretroviral therapy Prevalence of PAH and RV dysfunction among adolescents with and without HIV As shown in Table 1 , HIV-positive adolescents had a significantly greater median (IQR) PASP than controls did (p = 0.005) but had similar mean TAPSE (p = 0.158) and RV FAC (p = 0.207) values. Figure 1 shows that the prevalence of PAH and RV dysfunction was significantly greater among HIV-infected adolescents than among controls (p = 0.030 and p = 0.017, respectively). Figure 1: Prevalence of pulmonary arterial hypertension and RV dysfunction in subjects and controls Predictors of PAH and RV dysfunction Table 3 shows that PAH was not associated with any of the tested sociodemographic, clinical or immunological factors among the HIV-positive participants (p > 0.05, Table 3 ). However, adolescents with PAH had significantly faster heart and respiratory rates and lower packed cell volume (PCV) than controls did (Table IV). RV dysfunction was significantly associated with advanced disease (p = 0.002), HIV diagnosis at 10 years and above (p < 0.001) and HAART commencement at 10 years and above (p = 0.024) (Table 3 ). Additionally, those with RV dysfunction had significantly faster heart and respiratory rates and lower systolic blood pressure and PCV (Table 4 ). ( place Table 3 here; see end of document for Table 3 ) Table 3 Association of Sociodemographics, Clinical and Immunological with PAH and RV Dysfunction PAH RV dysfunction Yes No p value Yes No p value (n = 7) (n = 83) (n = 8) (n = 82) Age group, Years 10 to13 3 (10.0) 27 (90.0) 0.692 3(10.0) 27(90.0) 0.872 14 to 16 1 (3.3) 29 (96.7) 2(6.7) 28(93.3) 17 to 19 3 (10.0) 27 (27.0) 3(10.0) 27(90.0) Gender Male 2 (4.4) 43 (95.6) 0.238 3(6.7) 42(93.3) 0.459 Female 5 (11.1) 40 (88.9) 5(11.1) 40(88.9) Social class Upper 0 (0.0) 4 (100.0) 0.832 0(0.0) 4(100.0) 0.815 Middle 1 (9.1) 10 (90.9) 1(9.1) 10(90.9) Lower 6 (8.0) 69 (92.0) 7(9.3) 68(90.7) Orphan status Both parent alive 5 (9.1) 50 (90.9) 0.761 6(10.9) 49(89.1) 0.639 Only one alive 2 (6.5) 29 (93.5) 2(6.5) 29(93.5) Both dead 0 (0.0) 4 (100.0 0(0.0) 4(100.0) Age at diagnosis, years < 10 4 (5.2) 73 (94.8) 0.059 3 (3.9) 74 (96.1) < 0.001* ≥ 10 3 (23.1) 10 (76.9) 5(38.5) 8(61.5) Current ART regimen Nucleoside exposed 7 (8.6) 74 (91.4) 0.348 8(9.9) 73(90.1) 0.323 Protease inhibitor exposed 0 (0.0) 9 (100.0) 0(0.0) 9(100.0) WHO HIV clinical stage I-II 5 (10.2) 44 (89.8) 3 (4.3) 44 (95.7) 0.002* III-IV 2 (4.8) 39 (95.1) 0.442 5 (11.6) 38 (88.4) Age at the commencement of ART, years < 10 3 (4.5) 64 (95.5) 0.068 3 (4.5) 64 (95.5) 0.024* ≥ 10 4 (17.4) 19 (82.6) 5 (21.7) 18 (78.3) Duration of ART in months, months ≤ 60 2 (8.3) 22 (91.7) 0.915 2 (8.3) 22 (91.7) 0.151 61–120 2 (9.5) 19 (90.5) 4 (19.0) 17 (81.0) > 120 3 (6.7) 42 (93.3) 2 (4.4) 43 (95.6) CD4 count, cells/µL < 200 3 (8.6) 32 (91.4) 0.823 4 (11.4) 31 (88.6) 0.499 ≥ 200 4 (7.3) 51 (92.7) 4 (7.3) 51 (92.7) Viral load, copies/ml < 1000 5 (6.9) 67 (93.1) 0.555 6 (8.3) 66 (91.7) 0.711 ≥ 1000 2 (11.1) 16 (88.9) 2 (11.1) 16 (88.9) *Significant; PAH = Pulmonary arterial hypertension, RV dysfunction = Right Ventricular dysfunction, WHO = World Health Organization, HIV = Human Immunodeficiency Virus, ART = Antiretroviral therapy. Table 4: Association of Anthropometric and Clinical Factors with PAH and RV Dysfunction Parameters PAH RV dysfunction Yes No t value p value Yes No t value p value (n = 7) (n = 83) (n = 8) (n = 82) Weight, kg 44.3 ± 14.1 45.0 ± 13.5 -0.13 0.897 34.0 ± 8.4 45.4 ± 13.8 -2.57 0.065 Height, m 1.5 ± 0.1 1.5 ± 0.1 -0.02 0.986 1.5 ± 0.1 1.54 ± 0.1 -1.23 0.223 BMI, kg/m 2 17.6 ± 4.1 18.7 ± 3.7 -0.71 0.481 17.7 ± 4.3 18.6 ± 3.7 -0.47 0.637 BSA, m 2 1.5 ± 0.3 1.4 ± 0.2 0.87 0.389 1.3 ± 0.3 1.4 ± 0.2 -0.71 0.479 Pulse, beat/mins 99.9 ± 22.3 81.3 ± 12.8 3.46 0.001* 101.2 ± 20.9 81.9 ± 13.6 2.71 0.008* SBP, mmHg 107.1 ± 9.5 107.7 ± 9.3 -0.16 0.874 97.5 ± 5.0 108.1 ± 9.1 -2.31 0.023* DBP, mmHg 65.7 ± 5.3 65.5 ± 7.1 0.08 0.936 62.5 ± 5.0 65.6 ± 7.0 -0.89 0.378 Oxygen saturation, % 97.2 ± 1.2 97.8 ± 1.0 -1.43 0.157 98.3 ± 0.5 97.7 ± 1.1 0.98 0.332 Respiratory rate, cpm 19.1 ± 4.7 16.9 ± 1.4 3.12 0.002* 20.5 ± 5.7 16.9 ± 1.4 3.96 <0.001* PCV, % 32.3 ± 7.4 37.1 ± 4.8 -2.45 0.016* 25.7 ± 5.7 32.1 ± 47 4.14 <0.001* *Significant, HIV = Human Immunodeficiency Virus, kg = Kilogram, BSA = Body Surface Area, BMI = Body Mass Index; SBP = Systolic Blood Pressure; DBP = Diastolic Blood Pressure; mmHg = millimeter of mercury; cpm = cycles per minute, PCV = Packed Cell Volume; PAH = Pulmonary arterial hypertension, RV dysfunction = Right Ventricular dysfunction. Among the HIV-positive group, there was a significant association between PAH and RV dysfunction (p = 0.01): of the seven adolescents with PAH, four had RV dysfunction (i.e., four had both PAH and RV dysfunction, whereas the remaining three subjects had only PAH). Among the four patients with both PAH and RV dysfunction, two had both abnormal TAPSE and RV FAC, whereas the remaining two had only abnormal RV FAC. In the multivariable binary logistic regression model, as shown in Table 5 , only a reduced PCV was an independent predictor of PAH, whereas only age at diagnosis at 10 years and above independently predicted RV dysfunction. Table 5 Multivariate logistic regression results showing independent predictors of PAH and RV dysfunction. PAH Odds ratio 95% CI p value PAH Pulse rate 1.070 0.102–1.143 0.381 Respiratory rate 1.413 0.909–2.192 0.124 PCV 0.624 0.293–0.910 0.001* RV Dysfunction Age at diagnosis < 10 ≥ 10 1 3.849 1.339–7.011 0.043* WHO HIV clinical stage I-II III-IV 1 1.029 0.791–2.991 0.283 Age at the commencement of ART (Years) 2.019 0.543–4.901 0.381 Commencement of ART Before 2015 After 2015 1 0.919 0.291–2.391 0.691 SBP (mmHg) 1.048 0.928–1.184 0.449 PCV (%) 0.782 0.543–1.126 0.185 PASP (mmHg) 0.892 0.391–1.993 0.126 *Significant; PAH = Pulmonary arterial hypertension, RV dysfunction = Right ventricular dysfunction, WHO = World Health Organization, HIV = Human immunodeficiency virus, ART = Antiretroviral therapy, SBP = Systolic blood pressure; PCV = Packed cell volume; PASP = Pulmonary artery systolic pressure. Discussion As HIV-infected children survive into adolescence and adulthood, they are increasingly at risk of chronic diseases, including cardiovascular dysfunction, which may be asymptomatic and thus undetected without routine cardiac screening. In this cross-sectional study, we aimed to determine the prevalence and predictors of PAH and RV dysfunction among HIV-positive adolescents compared with controls at a tertiary specialist HIV clinic in Lagos, Nigeria. We observed the prevalence of PAH and RV dysfunction to be 7.8% and 8.9%, respectively, among HIV-infected adolescents. Anemia and delayed HIV diagnosis at 10 years and above were the only independent determinants of PAH and RV dysfunction, respectively, in our sample population. This is one of the few reports of PAH and RV dysfunction among adolescents from Nigeria or Africa. Our findings provide additional evidence of a high burden of PAH and RV dysfunction among HIV-infected adolescents. Prevalence of PAH and RV dysfunction among Nigerian HIV-positive adolescents The 7.8% prevalence of PAH (PASP ≥ 30 mmHg) we found is similar to the 7% and 7.9% reported by Chelo et al 28 and Sadoh et al 29 in Cameroon and Nigeria, respectively, but slightly lower than the 9.4% reported in a cross-sectional study by Kumari et al 30 in India and the 13% reported in another cross-sectional study by Idris et al 13 among HIV-positive children and adolescents in Indonesia. These differences may be due in part to the different cutoff values of the PASP used for defining PAH in these studies. Although the American Society of Echocardiography (ASE) recommended a PASP ≥ 30 mmHg as the diagnostic cutoff value, the authors used a PASP ≥ 13 25 mmHg, a PASP ≥ 37 mmHg 15 and a PASP ≥ 50 mmHg 31 , resulting in differences in reported prevalences. For example, when we explored a lower cutoff value of PASP ≥ 25 mmHg in our sample, we observed a higher prevalence of 12%, which was similar to that reported in the study conducted by Idris et al 13 , who used the same cutoff value. In contrast, a much higher cutoff of ≥ 50 mmHg yielded a prevalence of 0%, comparable to the 1.3% reported by Wubayehu et al 31 among HIV-positive adolescents in Addis Ababa. Curiously, however, despite the use of the same cutoff values, the PAH prevalence in our sample was seven to eight times higher than the 0.46% and 0% reported by Githinji et al. 16 and Majonga et al. 15 among Southern African and Zimbabwean cohorts and two times higher than the 3.6% reported by Miller et al. 14 in another Southern African study. We may speculate, albeit cautiously, that regional variations may exist in the prevalence of PAH among HIV-infected adolescents in Africa, possibly driven by variations in access to and timing of HAART. We found anemia to be an independent predictor of PAH among ALHIV, which is consistent with the findings of the studies by Chelo et al 28 in Cameroon and Kumari et al 30 in India, in which the prevalence of PAH was highest among participants who had anemia. Anemia causes pulmonary hypoxia, which leads to pulmonary vasoconstriction and eventually PAH. 28 Globally, anemia is common among people living with HIV, even with optimal disease control with HAART; approximately 40–50% of HIV-positive children, adolescents and adults have anemia globally. 32 Its aetio-pathogenesis is multifactorial, including direct viral effects on hematopoietic tissues such as the bone marrow; concomitant and opportunistic infections and diseases; immunopathies; and effects of drugs, among others. 33 Concerning the latter, zidovudine would have been a suspect, but it has been phased out of our HAART regimen for approximately five years. Thus, other factors, possibly nutritional, immune dysregulation and drug effects, are at play, and careful elucidation is needed for subsequent targeting with interventions (e.g., iron supplementation) 33 to slow progression to adverse outcomes such as PAH. Our observation that only one of the seven HIV-positive adolescents with PAH was symptomatic (cough, chest pain, dyspnea at rest, facial/ankle edema) is similar to that reported by Kumari et al. 30 in a study of cardiac abnormalities among HIV-infected Indian children and adolescents in whom all those with PAH were asymptomatic. This finding shows that PAH is often asymptomatic until the late stage, justifying the need for routine periodic echocardiographic screening for early diagnosis of PAH followed by appropriate ameliorative interventions before progression to RV dysfunction and right heart failure. Right ventricular dysfunction itself is an independent determinant of mortality from HIV-associated PAH. 13 Pathophysiologically, RV dysfunction may result from the progression of increased pulmonary artery pressure to increased RV afterload and hypertrophy; over time, a sustained increase in RV pressure leads to RV dilation and dysfunction and, eventually, right heart failure. Right ventricular dilatation also leads to tricuspid regurgitation, which further worsens heart failure. 10 , 22 We found that more HIV-infected adolescents had RV dysfunction (abnormal TAPSE < 1.6 cm or RV FAC < 34%) than their HIV-negative counterparts did (8.9% vs 1.1%). However, this prevalence was approximately three to four times lower than the 22% reported by Kuswiyanto et al 34 , the 32% reported by Githinji et al 16 and the 22% reported by Duru et al 9 in Indonesia, southern Africa, and Nigeria, respectively. This may be because more than half of our HIV-infected participants had early-stage HIV disease (WHO HIV clinical stages I and II), whereas the majority of those in the other studies had advanced-stage HIV disease (WHO HIV clinical stages III and IV). Advanced disease is associated with increased viral replication and chronic inflammation, leading to increased pulmonary vascular resistance and PAH and RV dysfunction. 16 Moreover, while we excluded those with current or past pulmonary tuberculosis, these patients were included in the latter studies. Chronic lung diseases such as tuberculosis are associated with an increased risk of RV dysfunction secondary to PAH. 16 Tuberculosis causes chronic inflammation and subsequent vasoconstriction of the pulmonary vasculature, leading to increased pulmonary artery pressure and PAH. 16 Additionally, varied diagnostic criteria for RV dysfunction may also explain the differing prevalences reported in the above studies. For example, while we defined RV dysfunction as TAPSE < 1.6 cm or RV FAC < 34%, the study by Duru et al 9 among Nigerian children and adolescents defined RV dysfunction with a lower cutoff value of TAPSE < 0.9 cm, possibly accounting for their much higher prevalence of 22%. To corroborate this, adjustment of our TAPSE cutoff to < 0.9 cm increased the prevalence of RV dysfunction among our HIV-positive cohort to 24% (making it comparable to the 22% reported in the study by Duru et al. 9 ). Moreover, whereas the majority of our participants were diagnosed with HIV at ages less than 10 years and commenced HAART at less than 10 years, the majority of those in the studies by Duru et al 9 , Githinji et al 16 and Kuswiyanto et a l 34 were diagnosed at ages above 10 years, partly accounting for the higher prevalence of RV dysfunction. Earlier age at HIV diagnosis followed by prompt initiation of HAART reduces viral replication and chronic inflammation, which in turn results in less smooth muscle cell proliferation of the pulmonary vasculature and, consequently, lower pulmonary artery pressure and a lower risk of PAH, RV afterload, RV hypertrophy and RV dysfunction. 15 However, the 8.9% prevalence of RV dysfunction was higher than the 2% reported in a study of Zimbabwean adolescents by Majonga et al. 15 The inclusion of older adolescents (mean age: 14.8 years) in our study could explain the higher prevalence of RV dysfunction than the lower prevalence of RV dysfunction reported in the study by Majonga et al 15 , which included younger adolescents (median age: 11.1 years). Moreover, the participants in the study by Majonga et a l 15 were mostly diagnosed at a younger age (age less than 10 years) and hence also commenced HAART earlier. Other workers also reported an association between increasing age and RV dysfunction among HIV-infected adolescents. 9 , 28 , 34 In general, PAH precedes and progresses to RV dysfunction. As expected, more HIV-infected participants in our study had PAH than RV dysfunction; hence, we assume that of the seven children with PAH, four may have progressed to RV dysfunction before our evaluation. Of these four subjects, two had both major and minor changes in RV function (abnormal TAPSE and RV FAC), whereas the remaining two subjects had only minor changes in RV function (abnormal RV FAC). Perhaps these minor changes in RV function usually precede major changes, further reinforcing advocacy for periodic echocardiographic screening for early detection of RV dysfunction before major RV dysfunction sets in by which time intervention may be late. Interestingly, three out of the seven HIV-positive adolescents who had RV dysfunction did not have PAH, suggesting that they may have had isolated RV dysfunction, RV dysfunction associated with left heart abnormalities (as two out of these also had associated left ventricular hypertrophy) or RV dysfunction may have been part of a global cardiomyopathic process, as documented in previous studies. 9 , 14 – 16 , 28 Predictors of HIV-associated PAH and RV dysfunction among Nigerian HIV-positive adolescents In resource-limited settings such as ours, the integration of periodic echocardiography into routine HIV care may be faced with issues of limited access due to challenges of cost, equipment and expertise in the setting of overall high disease burden. Thus, identifying risk factors associated with these cardiac complications may help to identify the most vulnerable subsets of HIV-positive adolescents who may be prioritized for such routine screening. Hence, we explored potential sociodemographic and clinical risk factors. Our finding of no statistically significant associations between PAH and most of the sociodemographic, clinical and immunologic characteristics (except PCV discussed earlier) aligns with the findings of studies by Idris et al 13 , Kumari et al 30 , Miller et al 14 , and Wubayehu et al 31 in Indonesia, India, southern Africa and northern Africa, respectively, but differs from those of Chelo et al 28 , where older age was significantly associated with PAH. Although our preliminary bivariate analyses revealed that RV dysfunction was associated with certain HIV demographics (age at diagnosis, age at commencement of ART, and advanced HIV) and clinical characteristics (pulse, respiratory rate, systolic blood pressure and PCV), only age at diagnosis remained an independent predictor. This suggests that the observed bivariate association between RV dysfunction and the other factors was possibly due to confounding associations between each of them and age at diagnosis. Older age at diagnosis of HIV implies that such children have a longer duration of exposure to uncontrolled viral replication with associated chronic inflammation and endothelial injury of the pulmonary vasculature before ART initiation. 16 This may subsequently translate to an increased risk of PAH, which may progress to RV dysfunction. In resource-limited regions such as ours, where out-of-pocket healthcare expenditures may limit universal access to echocardiography, priority may be given to HIV-infected children aged 10 years and above. Primarily, further strengthening of PMTCT services, especially in sub-Saharan Africa, will lead to early detection of HIV infection and prompt initiation of ART with a subsequent reduction in viral load, ultimately mitigating PAH and RV dysfunction. Strengths and limitations Our study builds on existing studies in Africa. We uniquely used two echocardiographic parameters to assess RV dysfunction, in addition to pulmonary artery pressure measurement, to assess PAH. However, a larger sample size may be warranted to more precisely determine the burden of PAH and RV dysfunction among HIV-affected adolescents. Although we included the whole range of adolescents in our sample, our noninclusion of younger pediatric age groups implies that our findings may not be generalizable outside of adolescence. The use of a single-center cross-sectional design also limits generalization to the larger population of HIV-positive adolescents outside our institution, and causality is not implied by our identified associations. Nonetheless, our findings largely agree with the few published reports on HIV-associated PAH and RV dysfunction from Nigeria and sub-Saharan Africa. To define RV dysfunction, we used cutoff values that were developed elsewhere, vis-à-vis the TAPSE and RV FAC. It is not known, but worthy of investigation, whether a different cutoff is more predictive of poor outcomes among Nigerian children than other cutoff values are. For example, a study by Oladimeji et al 35 reported that the lower limit of normal of the TAPSE for Nigerian adolescents (10–12-year-olds) is approximately 2.0 cm; whether this cutoff is better for Nigerian children than the more generic cutoff of 1.6 cm requires studies that compare the ability of the two to predict clinically important prognostic outcomes. Conclusion and recommendations Echocardiographically assessed PAH and RV dysfunction were more common among Nigerian HIV-positive adolescents accessing routine HIV care than among HIV-negative controls at a pediatric specialist hospital in Lagos. While the presence of PAH was independently predicted by PCV, RV dysfunction was associated with older age at diagnosis (age 10 years and above). These findings support enhanced early diagnosis and prompt treatment, especially with an optimized hematological profile (PCV) as a target, and the need to integrate periodic echocardiographic screening into routine HIV care. We also highlight the need for further studies—preferably multicenter prospective cohort studies—on PAH among HIV-infected children and its association with and/or progression to RV dysfunction. The potential impact of interventions, such as those that ameliorate anemia, on the progression and outcome of PAH/RV dysfunction is also worthy of exploration. Abbreviations AIDS: Acquired immunodeficiency virus ART: Anti-retroviral therapy HAART: Highly active antiretroviral therapy HIV: Human immunodeficiency virus HIV-CVD: HIV-associated cardiovascular diseases LV: left ventricle MSCH: Massey Street Children’s Hospital NCDs: noncommunicable diseases PAH: pulmonary artery hypertension PCV: Packed cell volume PASP: pulmonary artery systolic pressure RV: Right ventricle RV FAC: right ventricular fractional area change TAPSE: Tricuspid annular plane systolic excursion Declarations Ethics approval and consent to participate We conducted the study in accordance with the Declaration of Helsinki. We obtained ethical approval from the Health Research and Ethics Committee of Lagos State University Hospital (LREC/06/10/1785) and written parental consent and assent from the participants. Children with abnormal echocardiographic findings were referred to the Pediatric Cardiology Clinic for further evaluation and management. Consent for publication Not applicable Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding None Authors’ contributions CKA conceptualized, designed, and obtained data; analyzed, interpreted, drafted and revised the manuscript; and MOA, BAA, CAM, POU and FON assisted in study conceptualization, design, data analysis/interpretation, manuscript drafting and revision. AOS, AO and PO assisted with the study design and manuscript revision; additionally, AO assisted with the data collection. All the authors read and approved the final manuscript. Acknowledgment The authors express gratitude to the participating adolescents and their parents/guardians. We also thank the medical and nursing staff of the pediatric HIV and cardiology clinics of the Massey Street Children’s Hospital for their various types of support during the study. References Innes S, Patel K. Noncommunicable diseases in adolescents with perinatally acquired HIV-1 infection in high-income and low-income settings. Curr Opin HIV AIDS [Internet]. 2018 May;13(3):187–95. Available from: https://journals.lww.com/01222929-201805000-00005 Venkat Narayan KM, Miotti PG, Anand NP, Kline LM, Harmston C, Gulakowski R, et al. HIV and Noncommunicable Disease Comorbidities in the Era of Antiretroviral Therapy. JAIDS J Acquir Immune Defic Syndr. 2014 Sep;67(Supplement 1):S2–7. Lipshultz SE, Miller TL, Wilkinson JD, Scott GB, Somarriba G, Cochran TR, et al. Cardiac effects in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents: a view from the United States of America. J Int AIDS Soc. 2013 Jan;16(1):18597. Mengistu AD. 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Cardiac disease in adolescents with delayed diagnosis of vertically acquired HIV infection. Clin Infect Dis. 2013 Feb;56(4):576–82. Majonga ED, Rehman AM, Simms V, McHugh G, Mujuru HA, Nathoo K, et al. High prevalence of echocardiographic abnormalities in older HIV-infected children taking antiretroviral therapy. AIDS. 2018;32(18):2739. Githinji LN, Mahtab S, Zühlke L, Lawrenson J, Myer L, Gray D, et al. Cardiopulmonary dysfunction in perinatally HIV‐infected South African adolescents on antiretroviral therapy: baseline findings from the Cape Town Adolescent Antiretroviral Cohort. J Int AIDS Soc. 2019 Jul;22(7). Bigna JJ, Nansseu JR, Noubiap JJ. Pulmonary hypertension in the global population of adolescents and adults living with HIV: a systematic review and meta-analysis. Sci Rep. 2019 Dec;9(1):17–20. Sitbon O, Lascoux-Combe C, Delfraissy JF, Yeni PG, Raffi F, De Zuttere D, et al. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med. 2008;177(1):108–13. Quezada M, Martin-Carbonero L, Soriano V, Vispo V, Valencia E, Moreno V, et al. Prevalence and risk factors associated with pulmonary hypertension in HIV-infected patients on regular follow-up. AIDS. 2012 Jul;26(11):1387–92. Isasti G, Moreno T, Pérez I, Cabrera F, Palacios R, Santos J. High prevalence of pulmonary arterial hypertension in a cohort of asymptomatic HIV-infected patients. AIDS Res Hum Retroviruses. 2013 Feb;29(2):231–4. Kofi Owusu I. Echocardiographic Abnormalities in Patients with HIV Infection at Komfo Anokye Teaching Hospital, Ghana. J Gen Pract. 2014;02(02):3–8. Ryan JJ, Archer SL. The Right Ventricle in Pulmonary Arterial Hypertension: Disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circ Res. 2014 Jun;115(1):176–8. National AIDS & STIs Control Programme. National guidelnes for HIV prevention treatment and care. Abuja: Federal Ministry of Health; 2020. 1-210 p. Ferrand RA, Desai SR, Hopkins C, Elston CM, Copley SJ, Nathoo K, et al. Chronic lung disease in adolescents with delayed diagnosis of vertically acquired HIV infection. Clin Infect Dis. 2012 Jul;55(1):145–52. Duru CO, Udo PA, Lamina MO, Chinawa JM. Pulmonary Hypertension in Apparently Healthy Children in Southern Nigeria. J Coll Physicians Surg Pakistan. 2020;30(11):1175–9. Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, et al. Recommendations for Quantification Methods During the Performance of a Pediatric Echocardiogram : A Report From the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr. 2010;23(5):465–95. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015 Oct;46(4):903–75. Chelo D, Wawo E, Siaha V, Anakeu A, Ateba Ndongo F, Koki Ndombo PO, et al. Cardiac anomalies in a group of HIV-infected children in a pediatric hospital: an echocardiographic study in Yaounde, Cameroon. 2015;5(6). Wilson SE, Chinyere UC, Queennette D. Childhood acquired heart disease in Nigeria : an echocardiographic study from three centers. Afr Health Sci. 2014 Sep;14(3):609–16. S. DU, Nayar. DL, Mathews. DC. Cardiovascular Abnormalities in Hiv Infected Pediatric Population in Kerala. Int J Adv Res. 2017;5(1):561–5. Wubayehu T, Abebe W, Tefera E. Echocardiographic abnormalities in children and adolescents living with human immunodeficiency virus on highly active antiretroviral treatment. Cardiovasc J Afr. 2020;31(5):236–40. Cao G, Wang Y, Wu Y, Jing W, Liu J, Liu M. Prevalence of anemia among people living with HIV: A systematic review and meta-analysis. eClinicalMedicine. 2022;44(38). Obeagu EI, Obeagu GU, Ukibe NR, Oyebadejo SA. Anemia, iron, and HIV: Decoding the interconnected pathways: A review. Med (United States). 2024;103(2):E36937. Purniti PS. Pediatrica Indonesiana. 2011;51(4):207–12. Oladimeji AB, Lamina MO, Ubuane PO, Adekunle MO, Kehinde OA, Animasahun BA, et al. Echocardiographic reference z scores of right ventricular dimension and systolic function of children aged 5–12 years. Clin Exp Pediatr. 2023;66(5):215–22. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4966002","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":360462417,"identity":"f98d1753-62f1-42d8-9d93-38a6883b0a09","order_by":0,"name":"Cressida Kfunsei Amichoh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYBACg8MHQJQEhJfAxiAHog88wKPFsC0BVYsxWEsCHi3GbCiybAyJDWC9eLSYsfGYPfxRYSFv3t7++MODMrv0+WGHHwJtsZPTbcCuxYaNx9yY54yE4ZwzZ8wkEs4l5268nWYA1JJsbHYAhxb5HjNpxjaJBAmJHKCr2phzN85OAGk5kLgNhxaQwyR//gNqkX/++ENiW3264ez0D3i1GAO1SPA2gGxhMJBIbDucIC+dg98Wwza2MmmeYxKGM3hyQH45brhBOqfgQIIBbr8YHGPeJvmjpk5egv34448/yqrl5Wenb/7wocJODpcWLIaAVRoQqxwE5BtIUT0KRsEoGAUjAQAAY7ZbKsBMNvoAAAAASUVORK5CYII=","orcid":"","institution":"Massey Street Children's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Cressida","middleName":"Kfunsei","lastName":"Amichoh","suffix":""},{"id":360462420,"identity":"789f398a-e235-43e8-834e-6e6c0fae3422","order_by":1,"name":"Motunrayo Oluwabukola Adekunle","email":"","orcid":"","institution":"Lagos State University Teaching Hospital","correspondingAuthor":false,"prefix":"","firstName":"Motunrayo","middleName":"Oluwabukola","lastName":"Adekunle","suffix":""},{"id":360462422,"identity":"c90c02a7-c74e-4f29-b871-c56ebd750027","order_by":2,"name":"Cecilia Abimbola Mabogunje","email":"","orcid":"","institution":"Massey Street Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Cecilia","middleName":"Abimbola","lastName":"Mabogunje","suffix":""},{"id":360462423,"identity":"f543754f-e028-48e7-ba54-a11e4706d33b","order_by":3,"name":"Barakat Adeola Animasahun","email":"","orcid":"","institution":"Lagos State University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Barakat","middleName":"Adeola","lastName":"Animasahun","suffix":""},{"id":360462426,"identity":"3f58ff78-3cc9-43ba-a073-4f7e37a47b57","order_by":4,"name":"Peter Odion Ubuane","email":"","orcid":"","institution":"Lagos State University Teaching Hospital","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"Odion","lastName":"Ubuane","suffix":""},{"id":360462432,"identity":"f5857805-9f68-445b-ae44-b5a064c0d4c2","order_by":5,"name":"Abideen Olurotimi Salako","email":"","orcid":"","institution":"Nigerian Institute of Medical Research","correspondingAuthor":false,"prefix":"","firstName":"Abideen","middleName":"Olurotimi","lastName":"Salako","suffix":""},{"id":360462433,"identity":"4c9e0b2b-f0da-4dbb-8694-fe91561a3279","order_by":6,"name":"Adesola Olorunfemi","email":"","orcid":"","institution":"Massey Street Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Adesola","middleName":"","lastName":"Olorunfemi","suffix":""},{"id":360462437,"identity":"9b485d04-5cf5-49f0-874b-fb623c9edae3","order_by":7,"name":"Igoche David Peter","email":"","orcid":"","institution":"The Limi Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Igoche","middleName":"David","lastName":"Peter","suffix":""},{"id":360462439,"identity":"2cc67010-6f3a-4ce6-acd3-5cd42feb91c1","order_by":8,"name":"Fidelis Olisamedua Njokanma","email":"","orcid":"","institution":"Lagos State University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Fidelis","middleName":"Olisamedua","lastName":"Njokanma","suffix":""}],"badges":[],"createdAt":"2024-08-23 18:57:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4966002/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4966002/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":65904525,"identity":"7d5ee68b-9e54-48b6-8ee4-5abc44bc785b","added_by":"auto","created_at":"2024-10-04 08:21:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":125711,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of pulmonary arterial hypertension and RV dysfunction in subjects and controls\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4966002/v1/264dd17b704cb2fab8d817b1.png"},{"id":84448324,"identity":"161fb2e6-9ea2-4311-9c8e-fcec965321eb","added_by":"auto","created_at":"2025-06-12 06:17:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1885458,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4966002/v1/3f0be3ca-0deb-441f-b729-5880bad4485a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence and predictors of pulmonary arterial hypertension and right ventricular dysfunction in HIV-infected adolescents in Nigeria: a cross-sectional study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlobally, highly active antiretroviral therapy (HAART) has changed HIV infection from an acute, often fatal, illness to a lifelong manageable chronic disease.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Consequently, HIV-infected children now survive into adolescence and adulthood but at the expense of an increased risk of chronic non-communicable diseases (NCDs), including those of the cardiovascular system, which are mediated via direct viral and indirect mechanisms.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e These HIV-associated cardiovascular diseases (HIV-CVDs) are usually subclinical and, thus, often unrecognized, especially in early stages.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e HIV-CVD ranges from subtle abnormalities in cardiac size and function to more severe disorders, such as dilated cardiomyopathy, myocarditis, coronary artery disease, and pulmonary artery hypertension (PAH).\u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Notably, PAH is a progressive and fatal disorder culminating in RV dysfunction, which is, in turn, a major determinant of outcome and survival among HIV-infected individuals.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Unfortunately, the symptoms of PAH and RV dysfunction are non-specific and often similar to the cardiorespiratory symptoms of HIV-related opportunistic infections.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSeveral echocardiographic parameters can be used to non-invasively assess RV function; notably, the tricuspid annular plane systolic excursion (TAPSE) can be used to assess global RV function.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Additionally, the RV fractional area change (RV FAC), which can detect early RV changes, even when the TAPSE is normal.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e There is a paucity of published reports on the prevalence of PAH and RV dysfunction among HIV-infected children and adolescents globally, especially in Africa.\u003csup\u003e\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Most reports are from the adult population, with a global prevalence of 0.5\u0026ndash;38%.\u003csup\u003e17\u0026ndash;21\u003c/sup\u003e However, the findings in HIV-infected adults may not apply to adolescents, for example, because the latter and their organs are still growing. Furthermore, whereas much is known about HIV-associated left ventricular (LV) abnormalities, \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e considerably less is known about RV dysfunction in HIV-infected children and adolescents, despite being a possible indicator of the presence of PAH and a determinant of HIV-associated cardiac morbidity and mortality.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Thus, the early detection and management of PAH and its associated RV dysfunction among adolescents living with HIV (ALHIV) is important for halting or slowing progression to right heart failure and death. This may require the integration of periodic echocardiographic screening into routine HIV care, informed by relevant epidemiologic data. Additionally, the knowledge of predictors of PAH and RV dysfunction may guide targeted preventive interventions, as well as identifying subsets of ALHIV who may be prioritized for such screening where resources are limited. We thus aimed to determine the prevalence and predictors of PAH and RV dysfunction among HIV-infected adolescents in an HIV Clinic in Lagos, Nigeria, using echocardiographically measured pulmonary artery systolic pressure (PASP), TAPSE, and RV FAC.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eWe conducted this analytical cross-sectional study of HIV-infected children aged 10\u0026ndash;19 years, with sex- and age-matched HIV-negative controls, over four months (April to July 2023) at the Adolescents\u0026rsquo; HIV Clinic of Massey Street Children\u0026rsquo;s Hospital (MSCH), a 102-bed government-owned Pediatric hospital in Lagos Island. The MSCH serves as a referral center for primary and secondary health facilities across Lagos State and neighboring states. Its services include the care of HIV-infected children and adolescents, as well as general and specialist pediatric services such as cardiology services.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSample selection and sampling technique\u003c/h2\u003e \u003cp\u003eWe consecutively recruited HIV-infected adolescents aged 10\u0026ndash;19 years who had been attending the HIV outpatient clinic and were on HAART for at least six months. These adolescents had been previously confirmed to be HIV positive at enrollment in the Pediatric HIV Program on the basis of extant National Guidelines for HIV Management.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e We excluded those with current or recent acute illness in the preceding two weeks; a history and/or physical features suggestive of sickle cell anemia; congenital or acquired heart diseases; connective tissue diseases; pulmonary diseases; chronic renal disease; schistosomiasis; and drug therapy with potential cardiovascular effects. We also recruited age- and sex-matched healthy HIV-negative adolescents (confirmed negative with a rapid test according to National HIV guidelines\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e) with these exclusion criteria from general outpatient clinics.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSample size\u003c/h2\u003e \u003cp\u003eWe determined the sample size using the following formula for comparing two proportions:\u003c/p\u003e \u003cp\u003e \u003cem\u003en= ([Z\u003c/em\u003e \u003csub\u003e \u003cem\u003eα\u003c/em\u003e \u003c/sub\u003e \u003cem\u003e+ Z\u003c/em\u003e\u003csub\u003e\u003cem\u003eβ\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e]2[p\u003c/em\u003e\u003csub\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sub\u003e\u003cem\u003eq\u003c/em\u003e\u003csub\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sub\u003e\u0026thinsp;\u003cem\u003e+\u0026thinsp;p\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e\u003cem\u003eq\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e)/A\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e, where \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;minimum sample size per group; \u003cem\u003eZ\u003c/em\u003e\u003csub\u003e\u003cem\u003eα\u003c/em\u003e\u003c/sub\u003e = standard normal deviate (SND) at 95% confidence interval (CI)\u0026thinsp;=\u0026thinsp;1.96; \u003cem\u003eZ\u003c/em\u003e\u003csub\u003e\u003cem\u003eβ\u003c/em\u003e\u003c/sub\u003e = SND at the power of (1-β)\u0026thinsp;=\u0026thinsp;90%., i.e., 1.24; \u003cem\u003ep\u003c/em\u003e\u003csub\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;proportion of PAH among the HIV-positive group (7.0%)\u003csup\u003e24\u003c/sup\u003e [=\u0026thinsp;0.07] reported among Zimbabwean HIV-infected adolescents); \u003cem\u003ep\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;proportion of PAH among the HIV-negative control group (2%)\u003csup\u003e25\u003c/sup\u003e [=\u0026thinsp;0.02] reported among the Nigerian general population); \u003cem\u003eA\u003c/em\u003e\u0026thinsp;=\u0026thinsp;minimum assumed significant difference between groups set at =\u0026thinsp;0.1; n\u0026thinsp;=\u0026thinsp;86.73, approximately 90 per group, totaling 180. The participants were distributed equally across sex and age subgroups (10\u0026ndash;13 years, 14\u0026ndash;16 years, and 17\u0026ndash;19 years, representing early, middle and late adolescents, respectively), with 30 participants in each subgroup.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003eSociodemographic and clinical data\u003c/h2\u003e \u003cp\u003eSociodemographic (age, sex, and socioeconomic class) and clinical data (age at diagnosis, age at commencement of ART, type and duration of ART, and stage of HIV disease) were obtained from the parents and medical records and recorded in self-designed data collection forms. Socioeconomic class was derived with a scale for Nigerian children and was graded as low, medium or high.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eScreening examination\u003c/h2\u003e \u003cp\u003eWe conducted brief physical examinations to check for pallor, cyanosis, finger-clubbing, and standardized anthropometry (weight in kilograms) to the nearest 0.1 kg using a weight scale (Seca\u0026reg;, Germany) and height to the nearest 0.1 cm using a stadiometer (ADE\u0026reg;, Germany).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eEchocardiography\u003c/h2\u003e \u003cp\u003eWe performed transthoracic echocardiography using an M5 Mobile Digital Color Doppler Ultrasound System (MINDRAY, China) with a 2.0\u0026ndash; to 4.0-MHz phased array transducer for 2-dimensional, M-mode, color flow mapping and Doppler studies. According to the American Society of Echocardiography (ASE),\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e PAH was defined as a pulmonary artery systolic pressure (\u003cem\u003ePASP\u003c/em\u003e)\u0026thinsp;\u003cem\u003e\u0026ge;\u0026thinsp;30 mmHg\u003c/em\u003e, with a PASP equivalent to the RV systolic pressure derived from the tricuspid regurgitant velocity (TRV) via the simplified Bernoulli equation, 4 \u0026times; TRV.\u003csup\u003e27\u003c/sup\u003e We assessed RV systolic function with the TAPSE and RVFAC. Tricuspid annular plane systolic excursion was obtained in the apical 4-chamber view via the M-mode cursor placed across the lateral tricuspid annulus, and the total excursion was measured from the base of the heart to the apex at the end of systole. RV FAC was obtained from the apical 4-chamber view by tracing the RV endocardium both in systole and diastole from the annulus, along the free wall to the apex, and then to the annulus along the interventricular septum. It was calculated as the difference in the end-diastolic area and the end-systolic area divided by the end-diastolic area.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e We defined \u003cb\u003eRV dysfunction\u003c/b\u003e as a \u003cem\u003eTAPSE of \u0026lt;\u0026thinsp;1.6 cm or an RV FAC of \u0026lt;\u0026thinsp;34%\u003c/em\u003e.\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eHematological assays\u003c/h2\u003e \u003cp\u003eWe obtained 2 ml of venous blood from each participant into an EDTA bottle for estimation of the packed cell volume (PCV). We also assayed each participant\u0026rsquo;s CD4 count via a point-of-care device (VISITEC CD4 Advanced Disease Test Kit, Omega Diagnostics Ltd., Scotland), expressed semiquantitatively as \u0026lt;\u0026thinsp;200 and \u0026ge;\u0026thinsp;200 cells/\u0026micro;L.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eWe analyzed the data with SPSS version 26 (IBM, Inc., USA). Associations between categorical variables were assessed via the chi-square test or Fisher\u0026rsquo;s exact test. Comparisons of continuous variables between two groups were carried out via Student\u0026rsquo;s t test or the Mann‒Whitney U test if the data were skewed. Binary logistic regression was used to determine independent predictors of PAH and RV dysfunction. Statistical significance was set at a p value less than 0.05 at the 95% confidence interval (CI).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOverall, we recruited 215 participants. Of these, 35 were excluded because of recent or current tuberculosis.\u003c/p\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eSociodemographic and clinical characteristics of HIV-infected adolescents and controls\u003c/h2\u003e\n \u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows the socioclinical characteristics of the 180 adolescents (90 HIV-positive, 90 HIV-negative). There were more orphaned children in the HIV-infected group than in their HIV-negative counterparts (38.8% vs 4.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared with controls, HIV-infected adolescents also had lower diastolic blood pressure (65.6 vs 68.8 mmHg); other variables, such as anthropometrics, pulse, systolic blood pressure, oxygen saturation, respiratory rate and packed cell volume, were similar between them.\u003c/p\u003e\n \u003cp\u003eTable 1: Socioclinical and right ventricular characteristics of the participants\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHIV-positive (n = 90)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHIV-negative (n = 90)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP -value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge group (Years)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e10 \u0026ndash; 13\u003c/p\u003e\n \u003cp\u003e14-16\u003c/p\u003e\n \u003cp\u003e17-19\u003c/p\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e30 (33.3)\u003c/p\u003e\n \u003cp\u003e30 (33.3)\u003c/p\u003e\n \u003cp\u003e30 (33.3)\u003c/p\u003e\n \u003cp\u003e14.81 \u0026plusmn; 2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e30 (33.3)\u003c/p\u003e\n \u003cp\u003e30 (33.3)\u003c/p\u003e\n \u003cp\u003e30 (33.3)\u003c/p\u003e\n \u003cp\u003e14.52 \u0026plusmn; 2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e0.681\u003cstrong\u003e**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e45 (50.0)\u003c/p\u003e\n \u003cp\u003e45 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e45 (50.0)\u003c/p\u003e\n \u003cp\u003e45 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSocial class\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003cp\u003eMiddle\u003c/p\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e4 (4.4)\u003c/p\u003e\n \u003cp\u003e11 (12.2)\u003c/p\u003e\n \u003cp\u003e75 (83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e9 (10.0)\u003c/p\u003e\n \u003cp\u003e17 (18.9)\u003c/p\u003e\n \u003cp\u003e64 (71.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e4.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOrphan status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eBoth parents alive\u003c/p\u003e\n \u003cp\u003eOnly one alive\u003c/p\u003e\n \u003cp\u003eBoth dead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e55 (61.1)\u003c/p\u003e\n \u003cp\u003e31 (34.4)\u003c/p\u003e\n \u003cp\u003e4 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e86 (95.6)\u003c/p\u003e\n \u003cp\u003e4 (4.4)\u003c/p\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e31.644\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e44.94 \u0026plusmn; 13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e44.76 \u0026plusmn; 10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eHeight (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e1.54 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e1.57 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e-1.508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eBMI (weight/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e18.61 \u0026plusmn; 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e18.30 \u0026plusmn; 3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eBSA (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e1.39 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e1.41 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e-0.564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003ePulse rate (beat/mins)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e82.74 \u0026plusmn; 14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e83.38 \u0026plusmn; 13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e-0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e107.68 \u0026plusmn; 9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e109.82 \u0026plusmn; 10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e-1.554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eDBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e65.61 \u0026plusmn; 6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e68.82 \u0026plusmn; 10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e-2.535\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eOxygen saturation (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e97.75 \u0026plusmn; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e97.80 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e-0.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.744\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eRespiratory rate (cpm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e17.09 \u0026plusmn; 1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e17.24 \u0026plusmn; 1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e-0.637\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.525\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003ePCV (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e36.72 \u0026plusmn; 5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e37.01 \u0026plusmn; 5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003ePASP, mmHg\u003csup\u003e***\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e15.00 (11.9, 18.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e12.74 (9.7, 16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e2.812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7692%;\"\u003e\n \u003cp\u003eTAPSE, cm\u003c/p\u003e\n \u003cp\u003eRV FAC, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0385%;\"\u003e\n \u003cp\u003e2.23 \u0026plusmn; 0.4\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;54.53 \u0026plusmn; 13.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1154%;\"\u003e\n \u003cp\u003e2.16 \u0026plusmn; 0.3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;52.09 \u0026plusmn; 12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e1.419\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1.268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.5385%;\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e= chi square test;\u0026nbsp;*significant, **Independent Student\u0026rsquo;s t test,\u003csup\u003e\u0026nbsp;\u003c/sup\u003e***\u003csup\u003e\u0026nbsp;\u003c/sup\u003eMann‒Whitney U test HIV = Human immunodeficiency virus; kg = Kilogram, BSA = Body surface area, BMI = Body mass index; SBP = Systolic blood pressure; DBP = Diastolic blood pressure; mmHg = Millimeter of mercury; cpm = cycles per minute; PCV = Packed cell volume, PASP = Pulmonary artery systolic pressure, TAPSE = Tricuspid annular plane systolic excursion, cm = Centimeter, RV FAC = Right ventricular fractional area change.\u003c/em\u003e\u003c/p\u003e\n \u003cdiv\u003e\u003cbr\u003e\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eClinical and immunological profiles of HIV-infected adolescents\u003c/h2\u003e\n \u003cp\u003eApproximately half of the participants (47.8%) had early-stage HIV disease (WHO clinical stages I and II) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Approximately one-quarter (25.6%) commenced HAART after 10 years of age. Most (90.0%) were exposed to a nucleoside-based ART regimen. Most of them were asymptomatic at recruitment (95.6%, n\u0026thinsp;=\u0026thinsp;86).\u003c/p\u003e\n \u003cdiv\u003e\n \u003cp\u003eTable 2: Clinical and immunological profiles of the HIV-positive participants\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency (n=90)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercentage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWHO HIV clinical stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eI-II\u003c/p\u003e\n \u003cp\u003eIII-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e52.2\u003c/p\u003e\n \u003cp\u003e47.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCurrent ART regimen\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNucleoside exposed\u003c/p\u003e\n \u003cp\u003eProtease inhibitor exposed\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSymptoms and signs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e90.0\u003c/p\u003e\n \u003cp\u003e10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003eAsymptomatic\u003c/p\u003e\n \u003cp\u003eSymptomatic*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e95.6\u003c/p\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at the commencement of ART (years)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;10\u003c/p\u003e\n \u003cp\u003e\u0026ge;10\u003c/p\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003cp\u003e6.00 (2.0-10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e74.4\u003c/p\u003e\n \u003cp\u003e25.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of ART in months (months)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026le;60\u003c/p\u003e\n \u003cp\u003e60 to 120\u003c/p\u003e\n \u003cp\u003e\u0026gt;120\u003c/p\u003e\n \u003cp\u003eMedian (Q1 - Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003cp\u003e120.00 (58.3-172.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e26.7\u003c/p\u003e\n \u003cp\u003e23.3\u003c/p\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD4 count (cells/\u0026micro;L)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;200\u003c/p\u003e\n \u003cp\u003e\u0026ge;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e38.9\u003c/p\u003e\n \u003cp\u003e61.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eViral load (copies/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;1000\u003c/p\u003e\n \u003cp\u003e\u0026ge;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e80.0\u003c/p\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCommencement of ART**\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eBefore 2015\u003c/p\u003e\n \u003cp\u003eAfter 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e62.2\u003c/p\u003e\n \u003cp\u003e37.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cem\u003eHIV = Human Immunodeficiency Virus, WHO = World Health Organization, ART = Antiretroviral therapy\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003ePrevalence of PAH and RV dysfunction among adolescents with and without HIV\u003c/h2\u003e\n \u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, HIV-positive adolescents had a significantly greater median (IQR) PASP than controls did (p\u0026thinsp;=\u0026thinsp;0.005) but had similar mean TAPSE (p\u0026thinsp;=\u0026thinsp;0.158) and RV FAC (p\u0026thinsp;=\u0026thinsp;0.207) values. Figure\u0026nbsp;1 shows that the prevalence of PAH and RV dysfunction was significantly greater among HIV-infected adolescents than among controls (p\u0026thinsp;=\u0026thinsp;0.030 and p\u0026thinsp;=\u0026thinsp;0.017, respectively).\u003c/p\u003e\n \u003cp\u003eFigure\u0026nbsp;1: Prevalence of pulmonary arterial hypertension and RV dysfunction in subjects and controls\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003ePredictors of PAH and RV dysfunction\u003c/h2\u003e\n \u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows that PAH was not associated with any of the tested sociodemographic, clinical or immunological factors among the HIV-positive participants (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). However, adolescents with PAH had significantly faster heart and respiratory rates and lower packed cell volume (PCV) than controls did (Table IV). RV dysfunction was significantly associated with advanced disease (p\u0026thinsp;=\u0026thinsp;0.002), HIV diagnosis at 10 years and above (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and HAART commencement at 10 years and above (p\u0026thinsp;=\u0026thinsp;0.024) (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Additionally, those with RV dysfunction had significantly faster heart and respiratory rates and lower systolic blood pressure and PCV (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). (\u003cem\u003eplace\u003c/em\u003e Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cem\u003ehere; see end of document for\u003c/em\u003e Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n \u003cdiv\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAssociation of Sociodemographics, Clinical and Immunological with PAH and RV Dysfunction\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePAH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eRV dysfunction\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge group, Years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 to13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 to 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29 (96.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(93.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 to 19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (27.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43 (95.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42(93.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40 (88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40(88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSocial class\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.832\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.815\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMiddle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (90.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(90.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69 (92.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68(90.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOrphan status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBoth parent alive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50 (90.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.761\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49(89.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.639\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOnly one alive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29 (93.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29(93.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBoth dead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73 (94.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74 (96.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (76.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(61.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCurrent ART regimen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNucleoside exposed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74 (91.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.348\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(9.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73(90.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.323\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProtease inhibitor exposed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eWHO HIV clinical stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44 (89.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44 (95.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (95.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 (88.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at the commencement of ART, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64 (95.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.068\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64 (95.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.024*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (82.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (21.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (78.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of ART in months, months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.915\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u0026ndash;120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (81.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42 (93.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43 (95.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD4 count, cells/\u0026micro;L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32 (91.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31 (88.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51 (92.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51 (92.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eViral load, copies/ml\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67 (93.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.555\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66 (91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.711\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\n \u003cp\u003e\u003cem\u003e*Significant; PAH\u0026thinsp;=\u0026thinsp;Pulmonary arterial hypertension, RV dysfunction\u0026thinsp;=\u0026thinsp;Right Ventricular dysfunction, WHO\u0026thinsp;=\u0026thinsp;World Health Organization, HIV\u0026thinsp;=\u0026thinsp;Human Immunodeficiency Virus, ART\u0026thinsp;=\u0026thinsp;Antiretroviral therapy.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4: Association of Anthropometric and Clinical Factors with PAH and RV Dysfunction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 14%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 37%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePAH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 41%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRV dysfunction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9%;\"\u003e\n \u003cp\u003et value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9%;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 8%;\"\u003e\n \u003cp\u003et value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10%;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e(n = 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e(n = 83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e(n = 8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e(n = 82)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003eWeight, kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e44.3 \u0026plusmn; 14.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e45.0 \u0026plusmn; 13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e-0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.897\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e34.0 \u0026plusmn; 8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e45.4 \u0026plusmn; 13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e-2.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003eHeight, m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e1.5 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e1.5 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e-0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e1.5 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e1.54 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e-1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e0.223\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e17.6 \u0026plusmn; 4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e18.7 \u0026plusmn; 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e-0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.481\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e17.7 \u0026plusmn; 4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e18.6 \u0026plusmn; 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e-0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e0.637\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003eBSA, m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e1.5 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e1.4 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.389\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e1.3 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e1.4 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e-0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e0.479\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003ePulse, beat/mins\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e99.9 \u0026plusmn; 22.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e81.3 \u0026plusmn; 12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e3.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e101.2 \u0026plusmn; 20.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e81.9 \u0026plusmn; 13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e2.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003eSBP, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e107.1 \u0026plusmn; 9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e107.7 \u0026plusmn; 9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e-0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e97.5 \u0026plusmn; 5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e108.1 \u0026plusmn; 9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e-2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003eDBP, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e65.7 \u0026plusmn; 5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e65.5 \u0026plusmn; 7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.936\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e62.5 \u0026plusmn; 5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e65.6 \u0026plusmn; 7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e-0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e0.378\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003eOxygen saturation, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e97.2 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e97.8 \u0026plusmn; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e-1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e98.3 \u0026plusmn; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e97.7 \u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e0.332\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003eRespiratory rate, cpm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e19.1 \u0026plusmn; 4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e16.9 \u0026plusmn; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e20.5 \u0026plusmn; 5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e16.9 \u0026plusmn; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e3.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14%;\"\u003e\n \u003cp\u003ePCV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e32.3 \u0026plusmn; 7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e37.1 \u0026plusmn; 4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e-2.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12%;\"\u003e\n \u003cp\u003e25.7 \u0026plusmn; 5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9%;\"\u003e\n \u003cp\u003e32.1 \u0026plusmn; 47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8%;\"\u003e\n \u003cp\u003e4.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cem\u003e*Significant, HIV = Human Immunodeficiency Virus, kg = Kilogram, BSA = Body Surface Area, BMI = Body Mass Index; SBP = Systolic Blood Pressure; DBP = Diastolic Blood Pressure; mmHg = millimeter of mercury; cpm = cycles per minute, PCV = Packed Cell Volume; PAH = Pulmonary arterial hypertension, RV dysfunction = Right Ventricular dysfunction.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eAmong the HIV-positive group, there was a significant association between PAH and RV dysfunction (p\u0026thinsp;=\u0026thinsp;0.01): of the seven adolescents with PAH, four had RV dysfunction (i.e., four had both PAH and RV dysfunction, whereas the remaining three subjects had only PAH). Among the four patients with both PAH and RV dysfunction, two had both abnormal TAPSE and RV FAC, whereas the remaining two had only abnormal RV FAC.\u003c/p\u003e\n \u003cp\u003eIn the multivariable binary logistic regression model, as shown in Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e, only a reduced PCV was an independent predictor of PAH, whereas only age at diagnosis at 10 years and above independently predicted RV dysfunction.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariate logistic regression results showing independent predictors of PAH and RV dysfunction. PAH\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePAH\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulse rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.102\u0026ndash;1.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.381\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRespiratory rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.909\u0026ndash;2.192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.293\u0026ndash;0.910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eRV Dysfunction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e3.849\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.339\u0026ndash;7.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.043*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWHO HIV clinical stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eI-II\u003c/p\u003e\n \u003cp\u003eIII-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.791\u0026ndash;2.991\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.283\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at the commencement of ART (Years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.543\u0026ndash;4.901\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.381\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCommencement of ART\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eBefore 2015\u003c/p\u003e\n \u003cp\u003eAfter 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.291\u0026ndash;2.391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.691\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.928\u0026ndash;1.184\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.449\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCV (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.782\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.543\u0026ndash;1.126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.185\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePASP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.892\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.391\u0026ndash;1.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cem\u003e*Significant; PAH\u0026thinsp;=\u0026thinsp;Pulmonary arterial hypertension, RV dysfunction\u0026thinsp;=\u0026thinsp;Right ventricular dysfunction, WHO\u0026thinsp;=\u0026thinsp;World Health Organization, HIV\u0026thinsp;=\u0026thinsp;Human immunodeficiency virus, ART\u0026thinsp;=\u0026thinsp;Antiretroviral therapy, SBP\u0026thinsp;=\u0026thinsp;Systolic blood pressure; PCV\u0026thinsp;=\u0026thinsp;Packed cell volume; PASP\u0026thinsp;=\u0026thinsp;Pulmonary artery systolic pressure.\u003c/em\u003e\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAs HIV-infected children survive into adolescence and adulthood, they are increasingly at risk of chronic diseases, including cardiovascular dysfunction, which may be asymptomatic and thus undetected without routine cardiac screening. In this cross-sectional study, we aimed to determine the prevalence and predictors of PAH and RV dysfunction among HIV-positive adolescents compared with controls at a tertiary specialist HIV clinic in Lagos, Nigeria. We observed the prevalence of PAH and RV dysfunction to be 7.8% and 8.9%, respectively, among HIV-infected adolescents. Anemia and delayed HIV diagnosis at 10 years and above were the only independent determinants of PAH and RV dysfunction, respectively, in our sample population. This is one of the few reports of PAH and RV dysfunction among adolescents from Nigeria or Africa. Our findings provide additional evidence of a high burden of PAH and RV dysfunction among HIV-infected adolescents.\u003c/p\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003ePrevalence of PAH and RV dysfunction among Nigerian HIV-positive adolescents\u003c/h2\u003e \u003cp\u003eThe 7.8% prevalence of PAH (PASP ≥ 30 mmHg) we found is similar to the 7% and 7.9% reported by Chelo \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e and Sadoh \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e in Cameroon and Nigeria, respectively, but slightly lower than the 9.4% reported in a cross-sectional study by Kumari \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e in India and the 13% reported in another cross-sectional study by Idris \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e among HIV-positive children and adolescents in Indonesia. These differences may be due in part to the different cutoff values of the PASP used for defining PAH in these studies. Although the American Society of Echocardiography (ASE) recommended a PASP ≥ 30 mmHg as the diagnostic cutoff value, the authors used a PASP ≥ \u003csup\u003e13\u003c/sup\u003e25 mmHg, a PASP ≥ 37 mmHg\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e and a PASP ≥ 50 mmHg\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, resulting in differences in reported prevalences. For example, when we explored a lower cutoff value of PASP ≥ 25 mmHg in our sample, we observed a higher prevalence of 12%, which was similar to that reported in the study conducted by Idris \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, who used the same cutoff value. In contrast, a much higher cutoff of ≥ 50 mmHg yielded a prevalence of 0%, comparable to the 1.3% reported by Wubayehu \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e among HIV-positive adolescents in Addis Ababa.\u003c/p\u003e \u003cp\u003eCuriously, however, despite the use of the same cutoff values, the PAH prevalence in our sample was seven to eight times higher than the 0.46% and 0% reported by Githinji et al.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e and Majonga et al.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e among Southern African and Zimbabwean cohorts and two times higher than the 3.6% reported by Miller et al.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e in another Southern African study. We may speculate, albeit cautiously, that regional variations may exist in the prevalence of PAH among HIV-infected adolescents in Africa, possibly driven by variations in access to and timing of HAART.\u003c/p\u003e \u003cp\u003eWe found anemia to be an independent predictor of PAH among ALHIV, which is consistent with the findings of the studies by Chelo \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e in Cameroon and Kumari \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e in India, in which the prevalence of PAH was highest among participants who had anemia. Anemia causes pulmonary hypoxia, which leads to pulmonary vasoconstriction and eventually PAH.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Globally, anemia is common among people living with HIV, even with optimal disease control with HAART; approximately 40–50% of HIV-positive children, adolescents and adults have anemia globally.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e Its aetio-pathogenesis is multifactorial, including direct viral effects on hematopoietic tissues such as the bone marrow; concomitant and opportunistic infections and diseases; immunopathies; and effects of drugs, among others.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e Concerning the latter, zidovudine would have been a suspect, but it has been phased out of our HAART regimen for approximately five years. Thus, other factors, possibly nutritional, immune dysregulation and drug effects, are at play, and careful elucidation is needed for subsequent targeting with interventions (e.g., iron supplementation)\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e to slow progression to adverse outcomes such as PAH.\u003c/p\u003e \u003cp\u003eOur observation that only one of the seven HIV-positive adolescents with PAH was symptomatic (cough, chest pain, dyspnea at rest, facial/ankle edema) is similar to that reported by Kumari et al. \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e in a study of cardiac abnormalities among HIV-infected Indian children and adolescents in whom all those with PAH were asymptomatic. This finding shows that PAH is often asymptomatic until the late stage, justifying the need for routine periodic echocardiographic screening for early diagnosis of PAH followed by appropriate ameliorative interventions before progression to RV dysfunction and right heart failure.\u003c/p\u003e \u003cp\u003eRight ventricular dysfunction itself is an independent determinant of mortality from HIV-associated PAH.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Pathophysiologically, RV dysfunction may result from the progression of increased pulmonary artery pressure to increased RV afterload and hypertrophy; over time, a sustained increase in RV pressure leads to RV dilation and dysfunction and, eventually, right heart failure. Right ventricular dilatation also leads to tricuspid regurgitation, which further worsens heart failure.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e We found that more HIV-infected adolescents had RV dysfunction (abnormal TAPSE \u0026lt; 1.6 cm or RV FAC \u0026lt; 34%) than their HIV-negative counterparts did (8.9% vs 1.1%). However, this prevalence was approximately three to four times lower than the 22% reported by Kuswiyanto \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e, the 32% reported by Githinji \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e and the 22% reported by Duru \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e in Indonesia, southern Africa, and Nigeria, respectively. This may be because more than half of our HIV-infected participants had early-stage HIV disease (WHO HIV clinical stages I and II), whereas the majority of those in the other studies had advanced-stage HIV disease (WHO HIV clinical stages III and IV). Advanced disease is associated with increased viral replication and chronic inflammation, leading to increased pulmonary vascular resistance and PAH and RV dysfunction.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Moreover, while we excluded those with current or past pulmonary tuberculosis, these patients were included in the latter studies. Chronic lung diseases such as tuberculosis are associated with an increased risk of RV dysfunction secondary to PAH.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Tuberculosis causes chronic inflammation and subsequent vasoconstriction of the pulmonary vasculature, leading to increased pulmonary artery pressure and PAH.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Additionally, varied diagnostic criteria for RV dysfunction may also explain the differing prevalences reported in the above studies. For example, while we defined RV dysfunction as TAPSE \u0026lt; 1.6 cm or RV FAC \u0026lt; 34%, the study by Duru \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e among Nigerian children and adolescents defined RV dysfunction with a lower cutoff value of TAPSE \u0026lt; 0.9 cm, possibly accounting for their much higher prevalence of 22%. To corroborate this, adjustment of our TAPSE cutoff to \u0026lt; 0.9 cm increased the prevalence of RV dysfunction among our HIV-positive cohort to 24% (making it comparable to the 22% reported in the study by Duru et al.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e).\u003c/p\u003e \u003cp\u003eMoreover, whereas the majority of our participants were diagnosed with HIV at ages less than 10 years and commenced HAART at less than 10 years, the majority of those in the studies by Duru \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, Githinji \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e and Kuswiyanto \u003cem\u003eet a\u003c/em\u003el\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e were diagnosed at ages above 10 years, partly accounting for the higher prevalence of RV dysfunction. Earlier age at HIV diagnosis followed by prompt initiation of HAART reduces viral replication and chronic inflammation, which in turn results in less smooth muscle cell proliferation of the pulmonary vasculature and, consequently, lower pulmonary artery pressure and a lower risk of PAH, RV afterload, RV hypertrophy and RV dysfunction.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHowever, the 8.9% prevalence of RV dysfunction was higher than the 2% reported in a study of Zimbabwean adolescents by Majonga et al.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e The inclusion of older adolescents (mean age: 14.8 years) in our study could explain the higher prevalence of RV dysfunction than the lower prevalence of RV dysfunction reported in the study by Majonga \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003c/sup\u003e which included younger adolescents (median age: 11.1 years). Moreover, the participants in the study by Majonga \u003cem\u003eet a\u003c/em\u003el\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e were mostly diagnosed at a younger age (age less than 10 years) and hence also commenced HAART earlier. Other workers also reported an association between increasing age and RV dysfunction among HIV-infected adolescents.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn general, PAH precedes and progresses to RV dysfunction. As expected, more HIV-infected participants in our study had PAH than RV dysfunction; hence, we assume that of the seven children with PAH, four may have progressed to RV dysfunction before our evaluation. Of these four subjects, two had both major and minor changes in RV function (abnormal TAPSE and RV FAC), whereas the remaining two subjects had only minor changes in RV function (abnormal RV FAC). Perhaps these minor changes in RV function usually precede major changes, further reinforcing advocacy for periodic echocardiographic screening for early detection of RV dysfunction before major RV dysfunction sets in by which time intervention may be late.\u003c/p\u003e \u003cp\u003eInterestingly, three out of the seven HIV-positive adolescents who had RV dysfunction did not have PAH, suggesting that they may have had isolated RV dysfunction, RV dysfunction associated with left heart abnormalities (as two out of these also had associated left ventricular hypertrophy) or RV dysfunction may have been part of a global cardiomyopathic process, as documented in previous studies.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e–\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003ePredictors of HIV-associated PAH and RV dysfunction among Nigerian HIV-positive adolescents\u003c/h2\u003e \u003cp\u003eIn resource-limited settings such as ours, the integration of periodic echocardiography into routine HIV care may be faced with issues of limited access due to challenges of cost, equipment and expertise in the setting of overall high disease burden. Thus, identifying risk factors associated with these cardiac complications may help to identify the most vulnerable subsets of HIV-positive adolescents who may be prioritized for such routine screening. Hence, we explored potential sociodemographic and clinical risk factors. Our finding of no statistically significant associations between PAH and most of the sociodemographic, clinical and immunologic characteristics (except PCV discussed earlier) aligns with the findings of studies by Idris \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, Kumari \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, Miller \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, and Wubayehu \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e in Indonesia, India, southern Africa and northern Africa, respectively, but differs from those of Chelo \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003c/sup\u003e where older age was significantly associated with PAH.\u003c/p\u003e \u003cp\u003eAlthough our preliminary bivariate analyses revealed that RV dysfunction was associated with certain HIV demographics (age at diagnosis, age at commencement of ART, and advanced HIV) and clinical characteristics (pulse, respiratory rate, systolic blood pressure and PCV), only \u003cem\u003eage at diagnosis\u003c/em\u003e remained an independent predictor. This suggests that the observed bivariate association between RV dysfunction and the other factors was possibly due to confounding associations between each of them and age at diagnosis. Older age at diagnosis of HIV implies that such children have a longer duration of exposure to uncontrolled viral replication with associated chronic inflammation and endothelial injury of the pulmonary vasculature before ART initiation.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e This may subsequently translate to an increased risk of PAH, which may progress to RV dysfunction. In resource-limited regions such as ours, where out-of-pocket healthcare expenditures may limit universal access to echocardiography, priority may be given to HIV-infected children aged 10 years and above. Primarily, further strengthening of PMTCT services, especially in sub-Saharan Africa, will lead to early detection of HIV infection and prompt initiation of ART with a subsequent reduction in viral load, ultimately mitigating PAH and RV dysfunction.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eOur study builds on existing studies in Africa. We uniquely used two echocardiographic parameters to assess RV dysfunction, in addition to pulmonary artery pressure measurement, to assess PAH. However, a larger sample size may be warranted to more precisely determine the burden of PAH and RV dysfunction among HIV-affected adolescents. Although we included the whole range of adolescents in our sample, our noninclusion of younger pediatric age groups implies that our findings may not be generalizable outside of adolescence. The use of a single-center cross-sectional design also limits generalization to the larger population of HIV-positive adolescents outside our institution, and causality is not implied by our identified associations. Nonetheless, our findings largely agree with the few published reports on HIV-associated PAH and RV dysfunction from Nigeria and sub-Saharan Africa. To define RV dysfunction, we used cutoff values that were developed elsewhere, vis-à-vis the TAPSE and RV FAC. It is not known, but worthy of investigation, whether a different cutoff is more predictive of poor outcomes among Nigerian children than other cutoff values are. For example, a study by Oladimeji et al\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e reported that the lower limit of normal of the TAPSE for Nigerian adolescents (10–12-year-olds) is approximately 2.0 cm; whether this cutoff is better for Nigerian children than the more generic cutoff of 1.6 cm requires studies that compare the ability of the two to predict clinically important prognostic outcomes.\u003c/p\u003e \u003c/div\u003e "},{"header":"Conclusion and recommendations","content":"\u003cp\u003eEchocardiographically assessed PAH and RV dysfunction were more common among Nigerian HIV-positive adolescents accessing routine HIV care than among HIV-negative controls at a pediatric specialist hospital in Lagos. While the presence of PAH was independently predicted by PCV, RV dysfunction was associated with older age at diagnosis (age 10 years and above). These findings support enhanced early diagnosis and prompt treatment, especially with an optimized hematological profile (PCV) as a target, and the need to integrate periodic echocardiographic screening into routine HIV care. We also highlight the need for further studies—preferably multicenter prospective cohort studies—on PAH among HIV-infected children and its association with and/or progression to RV dysfunction. The potential impact of interventions, such as those that ameliorate anemia, on the progression and outcome of PAH/RV dysfunction is also worthy of exploration.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAIDS: Acquired immunodeficiency virus\u003c/p\u003e\n\u003cp\u003eART: Anti-retroviral therapy\u003c/p\u003e\n\u003cp\u003eHAART: Highly active antiretroviral therapy\u003c/p\u003e\n\u003cp\u003eHIV: Human immunodeficiency virus\u003c/p\u003e\n\u003cp\u003eHIV-CVD: HIV-associated cardiovascular diseases\u003c/p\u003e\n\u003cp\u003eLV: left ventricle\u003c/p\u003e\n\u003cp\u003eMSCH: Massey Street Children\u0026rsquo;s Hospital\u003c/p\u003e\n\u003cp\u003eNCDs: noncommunicable diseases\u003c/p\u003e\n\u003cp\u003ePAH: pulmonary artery hypertension\u003c/p\u003e\n\u003cp\u003ePCV: Packed cell volume\u003c/p\u003e\n\u003cp\u003ePASP: pulmonary artery systolic pressure\u003c/p\u003e\n\u003cp\u003eRV: Right ventricle\u003c/p\u003e\n\u003cp\u003eRV FAC: right ventricular fractional area change\u003c/p\u003e\n\u003cp\u003eTAPSE: Tricuspid annular plane systolic excursion\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eWe conducted the study in accordance with the Declaration of Helsinki. We obtained ethical approval from the Health Research and Ethics Committee of Lagos State University Hospital (LREC/06/10/1785) and written parental consent and assent from the participants. Children with abnormal echocardiographic findings were referred to the Pediatric Cardiology Clinic for further evaluation and management.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026rsquo; contributions\u003c/h2\u003e\n\u003cp\u003eCKA conceptualized, designed, and obtained data; analyzed, interpreted, drafted and revised the manuscript; and MOA, BAA, CAM, POU and FON assisted in study conceptualization, design, data analysis/interpretation, manuscript drafting and revision. AOS, AO and PO assisted with the study design and manuscript revision; additionally, AO assisted with the data collection. All the authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors express gratitude to the participating adolescents and their parents/guardians. We also thank the medical and nursing staff of the pediatric HIV and cardiology clinics of the Massey Street Children\u0026rsquo;s Hospital for their various types of support during the study.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eInnes S, Patel K. Noncommunicable diseases in adolescents with perinatally acquired HIV-1 infection in high-income and low-income settings. Curr Opin HIV AIDS [Internet]. 2018 May;13(3):187\u0026ndash;95. 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AIDS Res Hum Retroviruses. 2013 Feb;29(2):231\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eKofi Owusu I. Echocardiographic Abnormalities in Patients with HIV Infection at Komfo Anokye Teaching Hospital, Ghana. J Gen Pract. 2014;02(02):3\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eRyan JJ, Archer SL. The Right Ventricle in Pulmonary Arterial Hypertension: Disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circ Res. 2014 Jun;115(1):176\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eNational AIDS \u0026amp; STIs Control Programme. National guidelnes for HIV prevention treatment and care. Abuja: Federal Ministry of Health; 2020. 1-210 p.\u003c/li\u003e\n\u003cli\u003eFerrand RA, Desai SR, Hopkins C, Elston CM, Copley SJ, Nathoo K, et al. Chronic lung disease in adolescents with delayed diagnosis of vertically acquired HIV infection. Clin Infect Dis. 2012 Jul;55(1):145\u0026ndash;52.\u003c/li\u003e\n\u003cli\u003eDuru CO, Udo PA, Lamina MO, Chinawa JM. Pulmonary Hypertension in Apparently Healthy Children in Southern Nigeria. J Coll Physicians Surg Pakistan. 2020;30(11):1175\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eLopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, et al. Recommendations for Quantification Methods During the Performance of a Pediatric Echocardiogram : A Report From the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr. 2010;23(5):465\u0026ndash;95.\u003c/li\u003e\n\u003cli\u003eGali\u0026egrave; N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015 Oct;46(4):903\u0026ndash;75.\u003c/li\u003e\n\u003cli\u003eChelo D, Wawo E, Siaha V, Anakeu A, Ateba Ndongo F, Koki Ndombo PO, et al. Cardiac anomalies in a group of HIV-infected children in a pediatric hospital: an echocardiographic study in Yaounde, Cameroon. 2015;5(6).\u003c/li\u003e\n\u003cli\u003eWilson SE, Chinyere UC, Queennette D. Childhood acquired heart disease in Nigeria : an echocardiographic study from three centers. Afr Health Sci. 2014 Sep;14(3):609\u0026ndash;16.\u003c/li\u003e\n\u003cli\u003eS. DU, Nayar. DL, Mathews. DC. Cardiovascular Abnormalities in Hiv Infected Pediatric Population in Kerala. Int J Adv Res. 2017;5(1):561\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eWubayehu T, Abebe W, Tefera E. Echocardiographic abnormalities in children and adolescents living with human immunodeficiency virus on highly active antiretroviral treatment. Cardiovasc J Afr. 2020;31(5):236\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003eCao G, Wang Y, Wu Y, Jing W, Liu J, Liu M. Prevalence of anemia among people living with HIV: A systematic review and meta-analysis. eClinicalMedicine. 2022;44(38).\u003c/li\u003e\n\u003cli\u003eObeagu EI, Obeagu GU, Ukibe NR, Oyebadejo SA. Anemia, iron, and HIV: Decoding the interconnected pathways: A review. Med (United States). 2024;103(2):E36937.\u003c/li\u003e\n\u003cli\u003ePurniti PS. Pediatrica Indonesiana. 2011;51(4):207\u0026ndash;12.\u003c/li\u003e\n\u003cli\u003eOladimeji AB, Lamina MO, Ubuane PO, Adekunle MO, Kehinde OA, Animasahun BA, et al. Echocardiographic reference z scores of right ventricular dimension and systolic function of children aged 5\u0026ndash;12 years. Clin Exp Pediatr. 2023;66(5):215\u0026ndash;22.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"PAH, RV dysfunction, HIV, adolescents, children, sub-Saharan Africa, echocardiography","lastPublishedDoi":"10.21203/rs.3.rs-4966002/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4966002/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRight ventricular dysfunction (RV dysfunction) is a major cause of morbidity and mortality in HIV-associated pulmonary arterial hypertension (PAH). The clinical manifestations are non-specific and similar to the cardiorespiratory symptoms of comorbid opportunistic infections in HIV-infected individuals, thus leading to misdiagnosis. However, there is a paucity of data on the burden of HIV-associated PAH and RV dysfunction in Nigeria and sub-Saharan Africa. Hence, we evaluated the prevalence and predictors of PAH and RV dysfunction among adolescents living with HIV and uninfected controls.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis was an analytical, cross-sectional study of 90 HIV-infected adolescents and 90 HIV-negative controls aged 10\u0026ndash;19 years. Using transthoracic echocardiography, pulmonary artery pressure was estimated using pulmonary artery systolic pressure (PASP), and RV function was estimated using tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RV FAC). Pulmonary artery hypertension was defined as a PASP\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg and RV dysfunction with a TAPSE of \u0026lt;\u0026thinsp;1.6 cm or RV FAC\u0026thinsp;\u0026lt;\u0026thinsp;34%.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean ages of the HIV-positive adolescents and controls were 14.81\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 and 14.52\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 years, respectively (p\u0026thinsp;=\u0026thinsp;0.497). The prevalence of PAH was significantly greater in HIV-positive adolescents than in controls (7.8% vs 1.1%, p\u0026thinsp;=\u0026thinsp;0.030), as was the prevalence of RV dysfunction (8.9% vs 1.1%, p\u0026thinsp;=\u0026thinsp;0.017). PAH was independently associated with decreasing PCV (adjusted OR [95% CI]\u0026thinsp;=\u0026thinsp;0.62 [0.29\u0026ndash;0.91], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas RV dysfunction was independently associated with delayed age at diagnosis (age 10 years and above) (adjusted OR [95% CI]\u0026thinsp;=\u0026thinsp;3.85 [1.34\u0026ndash;7.01], p\u0026thinsp;=\u0026thinsp;0.043).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePulmonary artery hypertension and RV dysfunction were significantly more common among HIV-positive adolescents than among HIV-negative controls. Strengthening early diagnosis, prompt treatment with optimization of the hematologic profile and the integration of periodic echocardiography into routine HIV care are advocated.\u003c/p\u003e\u003ch2\u003eClinical trial number:\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e","manuscriptTitle":"Prevalence and predictors of pulmonary arterial hypertension and right ventricular dysfunction in HIV-infected adolescents in Nigeria: a cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-04 08:21:44","doi":"10.21203/rs.3.rs-4966002/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"be81ba3e-255b-4e8f-a663-a7c4bc4d44aa","owner":[],"postedDate":"October 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-12T06:09:27+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-04 08:21:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4966002","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4966002","identity":"rs-4966002","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}