Non-communicable diseases among people living with HIV, Victoria Chitepo provincial hospital: A retrospective cohort study, a secondary data analysis (2013-2023)

Non-communicable diseases among people living with HIV, Victoria Chitepo provincial hospital: A retrospective cohort study, a secondary data analysis (2013-2023) | 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 Non-communicable diseases among people living with HIV, Victoria Chitepo provincial hospital: A retrospective cohort study, a secondary data analysis (2013-2023) Kudzai Fortunate Vongai Chokuona, Munyaradzi Mukuzunga, Addmore Chadambuka, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4711585/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 Non-communicable diseases (NCDs) associated with human immunodeficiency virus (HIV) are emerging as the leading cause of death globally. An in depth analysis of the burden of NCDs in Manicaland province has not been done. We analyzed the NCDs/HIV data at Victoria Chitepo provincial hospital. Methods We conducted a retrospective cohort study from October 2013 to September 2023 using secondary data. Five major groups of NCDs were selected which were hypertension (HPT), diabetes mellitus (DM), chronic kidney injury (CKD), cancers and chronic respiratory illness. Kaplan Meier analysis and Cox proportional hazard analysis were performed. Risk ratios and hazard ratios with 95% confidence intervals were generated. Results A total of 974 patient records were reviewed with a median age of 43 (Q 1= 35; Q 3 = 51) years. Number of years on antiretroviral therapy (ART) (HR = 5.99, 95% CI: p < 0.001), age (HR = 4.78, 95%CI: p < 0.001) and DM/HIV comorbidity (HR = 4.63, 95% CI: p < 0.001) were hazards to HPT while being on efavirenz based regimen had a lower risk (HR = 0.47, 95% CI: p = 0.01) of developing HPT. Number of years on ART (HR = 9.89, 95% CI: p < 0.001), being on PI based regimen (HR = 4.66, 95% CI: p < 0.001), age (HR = 3.86, 95% CI, p < 0.001) and being on WHO stage 3 or 4 (HR = 3.75, 95% CI: p < 0.001) were hazards to DM. In 2022, the prevalence rate was 12 per 1000 people per year. Conclusion HPT and DM are the common NCDs among people living with HIV in this cohort. To minimize complications related to NCD/HIV comorbidities, we recommend routine screening of NCDs at monthly basis for early diagnosis and treatment. Non-communicable disease Human immunodeficiency virus ART Manicaland province Figures Figure 1 Figure 2 Introduction People who are living with HIV (PLHIV) have an increased risk of developing non-communicable diseases (NCDs) ( 1 , 2 ). NCDs associated with human immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS) are emerging as the leading cause of death globally (equivalent to 74% of all deaths), with a doubled risk in the HIV positive population than the non-AIDS related population ( 3 , 4 ). The gains in HIV care has led to an increase in older HIV patient cohorts associated with increased risk of NCDs ( 5 ). It is acceptable and feasible to integrate HIV and NCD services in resource limited settings ( 6 ). The global goal is: “To reduce the preventable and avoidable burden of morbidity, mortality and disability due to non-communicable diseases by means of multi-sectoral collaboration and cooperation at national, regional and global levels, so that populations reach the highest attainable standards of health and productivity at every age and those diseases are no longer a barrier to well-being or socioeconomic development”( 7 ). Annually; cardiovascular diseases, cancers, chronic respiratory diseases and diabetes mellitus account for 40%, 23%, 10% and 5% of NCD related deaths respectively globally ( 4 ). Globally, the top ten cancers with highest mortality rates are cervical cancer, prostate cancer, breast cancer, liver cancer, esophageal cancer, colorectal cancer, Kaposi sarcoma, stomach cancer, ovarian cancer and lung cancer ( 5 ). Cervical cancer has the highest mortality rate among women in developing countries (22 per 100000 population) and Zimbabwe is among the top five African countries with high incidence rate of 57 per 100000 population ( 5 ). In low and middle income countries; the NCD burden account for 80% of deaths with 30% of these deaths occurring before reaching 60 years ( 8 ). According to the 2022 World Health Organization (WHO) updates, NCDs in Africa caused 100000 to 400000 deaths annually ( 9 ). Zimbabwe has been experiencing a rise in NCDs in Africa with high age standardized disability adjusted life years (DALYs) ( 10 ). Another Zimbabwean study which used an individual multi-disease model evaluated that between 2015 and 2035, the most prevalent NCDs are chronic kidney injury (CKD), hypertension, depression and cancer with an estimation of 59% of PLHIV having at least one NCD by 2035 ( 11 ). Africa is facing the highest burden of diabetes mellitus, with Zimbabwe being amongst the countries with a high age standardized death rate of diabetes mellitus among females of 20–35 per 100000 population ( 5 ). African countries have also high prevalence of hypertension ranging from 24–34% among adults; with 82% of them being neither aware nor on treatment ( 5 ). A review on monitoring progress of the African region in achieving national commitments towards NCDs has been slowest ( 12 ). The risk of contracting NCDs include HIV infection, the ART regimens, aging, physical inactivity, use of tobacco, air pollution, unhealthy diets, dyslipidemia and alcohol abuse ( 4 , 13 , 14 ). The response to NCDs is anchored on early detection and screening combined with palliative care and treatment ( 4 ). The increased burden of the NCDs in Africa demands dependable estimation of the NCDs epidemiology to develop appropriate prevention and control measures ( 14 ). In high HIV burden settings, multimorbidity has been increasing among the adolescents and younger people with an increased risk of developing HIV related NCDs ( 15 , 16 ). A South African study reported that initial HIV response is more focused on mothers and children more than in older adults as they are assumed to be at a lower risk which increases the challenges in the management of NCDs and HIV in elderly people ( 17 ). In Uganda one in five HIV positive people had an NCD in 2018 ( 18 ). The control of the HIV/NCD burden requires the sensitization of the population through some of the HIV programs such as community engagement and defaulter tracing ( 19 ). The existence of more than one chronic disease in a person has been lacking adequate integrated healthcare which is a major health system challenge ( 20 ). At Victoria Chitepo Provincial Hospital (VCPH) an in depth analysis of the burden of NCDs has not been done. The burden of PLHIV developing NCDs has been on the rise globally but this has not been evaluated in the cohort managed at VCPH, which is the referral facility for Manicaland Province. We therefore analyzed the data of NCDs among PLHIV at VCPH from 2013 to 2023. Research Question What are factors associated with development of NCDs among PLHIV at VCPH over the past ten years? Broad Objective: To determine the risk factors associated with development of NCDs among PLHIV at VCPH from 2013 to 2023. Specific Objectives : To determine the demographic factors associated with development of NCDs among PLHIV at VCPH from 2013 to 2023. To determine the clinical factors associated with development of NCDs among PLHIV at VCPH from 2013 to 2023. To determine the prevalence of NCDs among PLHIV by ART regimen at VCPH from 2013 to 2023. To describe outcomes of HIV/NCDs comorbidity (alive, lost to follow up, dead) among PLHIV at VCPH from 2013 to 2023. To determine the trends of cumulative NCDs among PLHIV at VCPH from 2013 to 2023. Materials and Methods Study Design A retrospective cohort study of PLHIV initiated on ART from October 2013 to September 2023, using secondary data was carried out. Study setting The study was conducted at Victoria Chitepo Provincial Hospital (VCPH). VCPH is situated in Mutare City 3.4km north of Mutare town along the Mutare-Harare highway. Mutare is the third biggest city in Zimbabwe (after Harare and Bulawayo) and VCPH is the biggest government hospital in eastern Zimbabwe. VCPH is located in Mutare City which is in Manicaland province. It is a referral hospital for all the seven ( 7 ) districts of the province. The hospital serves a population of two million people in the province. By December 2022, 132755 people were on ART, in Manicaland Province (DHIS2). Study population Study participants were records of all PLHIV, enrolled on ART with case based data entered into the ePMS and patient booklets at VCPH for the cohorts from 2013 to 2023. Key informants were drawn from health care workers who work in the opportunistic infection department at VCPH. Sample size calculation Sample size was calculated using the Dobson formula n = z 2 p (1-p)/d 2 , with sensitivity analysis based on a study by Cheza et al (2019) on incidence of non-communicable diseases in HIV patients on ART in a developing country: Case of Zimbabwe’s Chitungwiza central hospital-A retrospective cohort study with a prevalence of 63% on being a female; and in another study by Pangmekeh et al (2019) on association between highly active antiretroviral therapy (HAART) and hypertension in persons living with HIV/AIDS at the Bamenda regional hospital, Cameroon with a prevalence of hypertension in PLHIV on ART of 36.44% ; at 95% confidence interval, precision (d 2 ) of 5% and a non-response rate of 10%. The minimum sample size for the patients’ records was 394. Sampling To increase the power of the study; all the 974 records of PLHIV initiated on ART who presented at VCPH from October 2013 to September 2023 were enrolled into the study using ePMS and patient booklets. Data capture and analysis Data which was captured from the ePMS and patient booklets which includes the age, sex, follow up status, CD4 count, ART regimen, ART start date, attendance records and the NCDs of the PLHIV. The five major groups of NCDs were selected from the records which are hypertension (HPT), diabetes mellitus (DM), chronic kidney injury (CKD), cancers and respiratory infections. Univariate analysis was performed through the calculation of proportions, means, medians and frequencies. Kaplan Meier analysis was performed using the same software, measuring against the event of interest: development of NCDs. The time to event was measured in months. Risk ratios and hazard ratios with 95% confidence intervals were generated and recorded from analysis. Cleaning of data was done before analysis. The Kaplan Meier and Logrank tests were used for survival analysis of the different groups of NCDs among PLHIV. Ethical considerations Permission to carry out the study was obtained from Manicaland Provincial Medical Directorate, Victoria Chitepo provincial hospital and Health Studies Office (HSO). Confidentiality of the patient records and study participants was maintained. No names were included on the key informant guide. Results A total of 974 patient booklets were successfully reviewed. The demographic and clinical characteristics are shown in Table 1 . Majority of the reviewed records constituted of females 565 (58.0%). Median age of the patients in years was 43 (Q 1= 35; Q 3 = 51). Out of the 159 (16.3%) who developed NCDs, 59.1% of them had hypertension. Table 1 Demographic and clinical characteristics of HIV/NCD cases, Victoria Chitepo Provincial Hospital, October 2013 – September 2023 Variable Category Frequency n (%) Sex Male 409 (42.0) Female 565 (58.0) Case classification Hypertension Diabetes mellitus Cancers Chronic kidney disease Respiratory infections 94 (9.7) 76 (7.8) 9 ((0.9) 6 (0.6) 3 (0.3) Outcome status Alive Lost to follow up Dead 864 (88.7) 87 (8.9) 23 (2.4) WHO stage Stage 1 Stage 2 Stage 3 Stage 4 400 (41.2) 331 (34.1) 217 (22.3) 24 (2.5) Age in years Median age (Q 1 ; Q 3 ) 43 (Q 1= 35;Q 3 = 51) Period of years on ART < 5 years ≥ 5 years 486 (49.9) 488 (50.1) Type of current regimen Nevirapine based Efavirenz based Dolutegravir based Protease inhibitor based 85 (8.7) 514 (52.8) 917 (94.2) 54 (5.5) In this study, PLHIV who were 40 years or older had 5.41 times risk of developing diabetes mellitus compared to those who were less than 40 years and it was statistically significant p < 0.001. Those who were initiated on dolutegravir had 1.12 times risk of developing diabetes mellitus compared to those who did not take dolutegravir and it was not statistically significant p = 0.82. PLHIV on WHO stage 3 or 4 (advanced HIV disease) had 2.72 times risk of developing diabetes mellitus compared to those who were on WHO stage 1 or 2. This was statistically significant (p < 0.001). HIV positive patients who were 40 years or older had 4.81 times risk of developing hypertension compared to those who were less than 40 years and this was statistically significant (p < 0.001). The probability of developing DM in PLHIV at 40 years and above was higher than in those below 40 years and it was statistically significant (p < 0.001). The probability of developing diabetes mellitus in PLHIV increased with increasing years on ART and it was statistically significant (p < 0.001). The probability of developing diabetes mellitus among PLHIV was not different among DTG users and DTG non-users and it was not statistically significant (p = 0.43). The probability of developing diabetes mellitus among PLHIV initiated on EFV based regimen is lower among EFV based regimen users than EFV based regimen non-users and it is statistically significant (p = 0.001). The probability of developing diabetes mellitus among PLHIV initiated on PI based regimen is higher among PI based regimen users than PI based regimen non-users and it was statistically significant (p < 0.001). The probability of developing hypertension among PLHIV increased with increasing number of years on ART and it statistically significant (p < 0.001). The probability of developing hypertension in PLHIV at 40 years and above was higher than in those below 40 years and it was statistically significant (p < 0.001). The probability of developing hypertension in PLHIV was higher in females than males but it was not statistically significant (p = 0.37). Controlling for gender and other variables (Fig. 1 and Table 2 ); the hazard for hypertension was 5.99 times higher in patients who had 5 or more years on ART compared to those who were on ART for less than 5 years and it was statistically significant (p < 0.001). Other hazards were being 40 years and above and being diabetic. There was approximately 53% lower risk of developing hypertension in the patients on efavirenz based regimen compared to non-users of efavirenz based regimen. Table 2 Cox proportional hazards for development of hypertension Variable Hazard ratio p value ART period (≥ 5, < 5) 5.99 < 0.001 Age group (≥ 40, < 40) 4.78 < 0.001 Diagnosed DM (yes, no) 4.63 < 0.001 WHO stage (3 or 4, 1 or 2) 2.08 0.09 NVP based (yes, no) 0.92 0.34 PI based (yes, no) 0.69 0.38 DTG based (yes, no) 0.66 0.40 EFV based (yes, no) 0.47 0.01 Sex (male, female) 0.69 0.09 The risk of developing DM was 9.89 times higher in patients who had 5 or more years on ART compared to those who had less than 5 years and this was statistically significant (p < 0.001). The other hazards to development of DM were being on PI based regimen, being greater than 40 years, being at WHO stage 3 or 4 and having hypertension. The hazard for diabetes mellitus was less for nevirapine based and efavirenz based regimens. However, there was no statistical significance between dolutegravir use and development of DM (Fig. 2 and Table 3 ). Table 3 Cox proportional hazards for development of diabetes mellitus Variable Hazard ratio p value ART period (≥ 5,<5) 9.89 < 0.001 PI based (yes, no) 4.66 < 0.001 Age group (≥ 40,<40) 3.86 < 0.001 WHO stage (3 or 4, 1 or 2) 3.75 < 0.001 Diagnosed of HPT (yes, no) 3.52 < 0.001 DTG (yes, no) 1.70 0.34 EFV based (yes, no) 1.03 0.91 NVP based (yes, no) 0.93 0.87 Sex (male, female) 0.98 0.94 Majority of PLHIV in this study had hypertension 94 (9.7%) and diabetes mellitus 76 (7.8). In our study, with total records reviewed of PLHIV of 974 and 159 NCDs, the prevalence rate was approximately 17 per 100 people per year in Manicaland province. A total of 6 (0.6%) PLHIV died from HPT/HIV comorbidity, 7 (0.7%) from DM/HIV comorbidity, 1 (0.1%) from cervical cancer/HIV comorbidity and 1 (0.1%) from CKD/HIV comorbidity in this cohort. A total of 15 NCD/HIV deaths out of the 159 PLHIV who developed NCDs gave an approximate case fatality rate of 1 per 10 PLHIV with NCDs per year. Discussion The highest NCD among PLHIV in this cohort was hypertension (HPT). This hypertension results from prothrombotic changes and inflammation caused by HIV as evidenced by Chastain et al ( 21 ). Aging in PLHIV was directly associated with development of hypertension as the exposure to HIV also increased. Similarly, Chastain et al and Daniel et al evidenced that the time on ART, the various types of regimens and the duration of HIV diagnosis have been associated with hypertension ( 21 , 22 ). The survival of PLHIV with HPT/HIV comorbidity reduced with age as they deteriorated more over time with aging and immunosuppression thereby shortening their lifespan. Similarly, in another study in Poland, the increase in duration with HIV disease and aging has been directly associated with CVD risk ( 23 ). As PLHIV were mostly screened on the yearly routine hospital visit, it delayed the diagnosis and treatment of the hypertension among other NCDs. Delayed diagnosis and treatment of hypertension can be linked to the high morbidity and mortality among these PLHIV as previously evidenced in an American study ( 21 ). A high case fatality rate was evidenced in diabetics in this retrospective cohort study compared to other NCDs. Management of both type 1 and type 2 diabetes mellitus can be critical as they both depend on the dietary and exercise lifestyle other than medication. Moreover, the risk of developing diabetes mellitus increased with age and years on ART from our study. A previous study in Iran by Hadavandsiri et al supported that glucose tolerance impairment increased with age ( 24 ). However, Bujuma et al also evidenced that exposure to ART and increasing years on ART was significantly associated with development of diabetes mellitus. In contrary, PLHIV on efavirenz or nevirapine in our study had higher chances of survival from developing diabetes mellitus compared to those on other regimens. This could be due to the lower influence on metabolic syndrome of non-nucleoside reverse transcriptase inhibitors (NNRTI) compared to other ART classes leading to reduced risk of hyperglycemia, dyslipidemia and hypertension related, as previously evidenced by Nguyen et al ( 25 ). WHO stage 3 or 4 also increased the risk of developing diabetes mellitus due to the HIV immunocompromised state. Switching of regimens is thereby recommended to monitor glucose metabolism ( 21 , 26 , 27 ). The potential risk of developing hyperglycemia due to various ART switches and HIV metabolic syndrome reduced the survival of PLHIV as evidenced in our study. In contrary to our study findings, patients who were on WHO stage 1 had higher risk of developing diabetes mellitus compared to other clinical stages in an Ethiopian study ( 28 ). However, in another study in Kenya, WHO staging had no significant association with development of NCDs ( 29 ). The immune suppression due to cervical cancer/HIV comorbidity resulted in death of one of the PLHIV in the study. We have noted a low number of cancer/NCD cases in this cohort and this has also been reported by Cheza et al in Zimbabwe that cancers have the lowest incidence rate compared to other NCDs ( 8 ). Early cervical cancer screening and the human papilloma virus vaccine reduced the cancer incidence thereby reducing the cervical cancer/HIV related mortality ( 30 ). Our study had an HIV positive patient who also suffered chronic kidney disease and died. This could be attributed to poorly controlled HIV and exposure to other ART regimens which causes cytopathic effect to the glomerular filtration leading to renal failure as supported by Alfano et al, Naicker et al and other researchers ( 31 – 34 ). Although our study reported the least number of PLHIV with respiratory illnesses such as asthma, all of them were in WHO stage 3 in ART initiation which is characterized by HIV/AIDS due to the weakened immunity. The use of ART has been evidenced to reduce respiratory infections/HIV related mortality ( 35 – 37 ). Dolutegravir has been hypothesized to cause insulin resistance through the chelation of its cofactor, the magnesium ions, thereby increasing the risk of hyperglycemia. However, our study evidenced that there was no statistical significance between DTG use and development of diabetes mellitus. DTG was combined with other regimens giving better cardio metabolic profile, with DTG associated with high viral load suppression and the other regimens in the combination controlling metabolism. Moreover, our study constituted a 94% coverage of DTG users which could make the non-diabetic DTG users override the diabetic DTG users in analysis. Supporting evidence of using combined regimens to control metabolism has been reported by Tripathi et al ( 38 ). Protease inhibitor based regimen was a hazard to diabetes mellitus in this study group. This follows as PI based regimens produce enzymes that catalyze human proteins involved in homeostasis, metabolism and cell growth thereby inducing impaired glucose tolerance ( 39 , 40 ). This increases the risk of developing hyperglycemia. Hughes et al also evidenced that longer duration on protease inhibitors increased the risk of developing diabetes mellitus ( 41 ). In our study, one in five PLHIV had an NCD. Similarly, in Uganda one in five HIV positive people had an NCD ( 18 ). The similar study findings could be due to similar country policies which are against gays and lesbians. Moreover, the economic settings in Zimbabwe and Uganda are similar as both are low resource settings. In Zimbabwe, just like other Sub-Saharan Africa countries; multimorbidity has been increasing among the adolescents and younger people with an increased risk of developing HIV related NCDs ( 15 , 16 ). Limitations On updating the patient booklets, some of the files were disposed with information of interest such as previous ART history and patients who deceased five or more years ago, thereby eliminating some PLHIV from the cohort study. Some patients who were lost to follow up and could not be determined their interval when they were out of the study. Recommendations and conclusion Hypertension and diabetes mellitus are the common NCDs among PLHIV due to the metabolic syndrome from HIV and the various ART regimens, causing high morbidity and mortality in this cohort. To minimise complications related to these NCD/HIV comorbidities, we recommend routine screening of NCDs at monthly basis for early diagnosis and treatment. Declarations Competing interests The authors declare that they have no competing interests both financial and non-financial. Author Contribution Authors’ contributions KC: conception, design, acquisition, analysis and interpretation of data and drafting the manuscript. MM: conception, design, acquisition, analysis and interpretation of data and drafting the manuscript. TJ: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. AC: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. GS: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. NG: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. MT: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. All authors read and approved the final manuscript. Acknowledgements The authors acknowledge the Manicaland Provincial Medical Directorate for their support in conducting this study. The authors are also thankful to the Zimbabwe MPH-FETP program and Centers for Disease Control and Prevention (CDC) Zimbabwe for technical assistance. Data Availability Data availability statement"The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request." References George S, McGrath N, Oni T. The association between a detectable HIV viral load and non-communicable diseases comorbidity in HIV positive adults on antiretroviral therapy in Western Cape, South Africa. BMC Infectious Diseases. 2019 Apr 27;19(1):348. NCD Alliance [Internet]. 2012 [cited 2023 Feb 16]. 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HIV-Associated Lung Infections and Complications in the Era of Combination Antiretroviral Therapy [Internet]. [cited 2023 Sep 7]. Available from: https://www.atsjournals.org/doi/epdf/10.1513/pats.201009-059WR?role=tab S C, M L. Respiratory infections in HIV-infected adults: epidemiology, clinical features, diagnosis and treatment. Current opinion in pulmonary medicine [Internet]. 2013 May [cited 2023 Sep 7];19(3). Available from: https://pubmed.ncbi.nlm.nih.gov/23422413/ Incidence of diabetes mellitus in a population-based cohort of HIV-infected and non-HIV-infected persons: the impact of clinical and therapeutic factors over time. - Abstract - Europe PMC [Internet]. [cited 2023 Sep 5]. Available from: https://europepmc.org/article/MED/24673640 Ravindra PV, Girish TK. Role of Proteases in Diabetes and Diabetic Complications. In: Chakraborti S, Dhalla NS, editors. Proteases in Physiology and Pathology [Internet]. Singapore: Springer; 2017 [cited 2023 Dec 6]. p. 289–96. Available from: https://doi.org/10.1007/978-981-10-2513-6_13 Lien LF, Feinglos MN. Protease Inhibitor-Induced Diabetic Complications. Drug-Safety. 2005 Mar 1;28(3):209–26. Hughes CA, Cashin RP, Eurich DT, Houston S. Risk factors for new-onset diabetes mellitus in patients receiving protease inhibitor therapy. Can J Infect Dis Med Microbiol. 2005;16(4):230–2. 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-4711585","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":337602923,"identity":"bd27c4d1-9f62-421c-8a8e-12efbc525cc6","order_by":0,"name":"Kudzai Fortunate Vongai Chokuona","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYBACCQYGAyCSY2BgbwByDSyI1mLMwMBzAKRFglgtDEAtEglQPiEgOSN584cfBQaJ/TOfX93wo0CCgb+9OwGvFmmJtALDHgODxBm3c8pu9gAdJnHm7Aa8WuQkcgwSeAz+GBtI56Td4AFqMZDIJazl4B8DA2MDyTNpN/8Qo0VaIsewmcfAQM5Agv3YbaJskex5VswsA9QicSaH7baMgQQPQb9IHE/e/PHNHwMe/vbjz26++WMjx9/ei18LEuAxAJPEKgcB9gekqB4Fo2AUjIIRBAB9nkF2tyhHvgAAAABJRU5ErkJggg==","orcid":"","institution":"University of Zimbabwe","correspondingAuthor":true,"prefix":"","firstName":"Kudzai","middleName":"Fortunate Vongai","lastName":"Chokuona","suffix":""},{"id":337602924,"identity":"546435d9-b9bc-4b58-b27a-e3cd54dd0130","order_by":1,"name":"Munyaradzi Mukuzunga","email":"","orcid":"","institution":"Manicaland Provincial Medical Directorate","correspondingAuthor":false,"prefix":"","firstName":"Munyaradzi","middleName":"","lastName":"Mukuzunga","suffix":""},{"id":337602927,"identity":"44dfae52-75fe-4ee8-be56-35c7c899c6af","order_by":2,"name":"Addmore Chadambuka","email":"","orcid":"","institution":"University of Zimbabwe","correspondingAuthor":false,"prefix":"","firstName":"Addmore","middleName":"","lastName":"Chadambuka","suffix":""},{"id":337602928,"identity":"5636d59a-6dec-43b7-8c1f-98420ca14370","order_by":3,"name":"Tsitsi Patience Juru","email":"","orcid":"","institution":"University of Zimbabwe","correspondingAuthor":false,"prefix":"","firstName":"Tsitsi","middleName":"Patience","lastName":"Juru","suffix":""},{"id":337602929,"identity":"910011de-ed92-4658-9250-6f21ec7dcc54","order_by":4,"name":"Notion Tafara Gombe","email":"","orcid":"","institution":"University of Zimbabwe","correspondingAuthor":false,"prefix":"","firstName":"Notion","middleName":"Tafara","lastName":"Gombe","suffix":""},{"id":337602930,"identity":"82dea3d6-f83b-4457-8126-a42637cd33ff","order_by":5,"name":"Gerald Shambira","email":"","orcid":"","institution":"University of Zimbabwe","correspondingAuthor":false,"prefix":"","firstName":"Gerald","middleName":"","lastName":"Shambira","suffix":""},{"id":337602931,"identity":"1a96023d-2924-4019-a37d-1bcec4b36341","order_by":6,"name":"Mufuta Tshimanga","email":"","orcid":"","institution":"University of Zimbabwe","correspondingAuthor":false,"prefix":"","firstName":"Mufuta","middleName":"","lastName":"Tshimanga","suffix":""}],"badges":[],"createdAt":"2024-07-09 11:12:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4711585/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4711585/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63271613,"identity":"424bd52c-116b-40e6-a88c-1cae3b56ffff","added_by":"auto","created_at":"2024-08-26 11:27:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":70873,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCox proportional hazard analysis for development of HPT, VCPH, 2013-2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4711585/v1/99839509574367e4d16e0098.png"},{"id":63271614,"identity":"6a02c7d5-6680-4205-81e7-d0292daeb26c","added_by":"auto","created_at":"2024-08-26 11:27:35","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":246519,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCox proportional hazard analysis for development of DM, VCPH, 2013-2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4711585/v1/52dced9e75bea494a6bceb8b.jpeg"},{"id":66890425,"identity":"2a5d704a-2266-4f42-a726-267ca69f19c9","added_by":"auto","created_at":"2024-10-17 14:32:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":892355,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4711585/v1/6b306e51-6500-43aa-b09d-7d8cc9fa6dc5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Non-communicable diseases among people living with HIV, Victoria Chitepo provincial hospital: A retrospective cohort study, a secondary data analysis (2013-2023)","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePeople who are living with HIV (PLHIV) have an increased risk of developing non-communicable diseases (NCDs) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). NCDs associated with human immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS) are emerging as the leading cause of death globally (equivalent to 74% of all deaths), with a doubled risk in the HIV positive population than the non-AIDS related population (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The gains in HIV care has led to an increase in older HIV patient cohorts associated with increased risk of NCDs (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). It is acceptable and feasible to integrate HIV and NCD services in resource limited settings (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe global goal is: \u0026ldquo;To reduce the preventable and avoidable burden of morbidity, mortality and disability due to non-communicable diseases by means of multi-sectoral collaboration and cooperation at national, regional and global levels, so that populations reach the highest attainable standards of health and productivity at every age and those diseases are no longer a barrier to well-being or socioeconomic development\u0026rdquo;(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Annually; cardiovascular diseases, cancers, chronic respiratory diseases and diabetes mellitus account for 40%, 23%, 10% and 5% of NCD related deaths respectively globally (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGlobally, the top ten cancers with highest mortality rates are cervical cancer, prostate cancer, breast cancer, liver cancer, esophageal cancer, colorectal cancer, Kaposi sarcoma, stomach cancer, ovarian cancer and lung cancer (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Cervical cancer has the highest mortality rate among women in developing countries (22 per 100000 population) and Zimbabwe is among the top five African countries with high incidence rate of 57 per 100000 population (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn low and middle income countries; the NCD burden account for 80% of deaths with 30% of these deaths occurring before reaching 60 years (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). According to the 2022 World Health Organization (WHO) updates, NCDs in Africa caused 100000 to 400000 deaths annually (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Zimbabwe has been experiencing a rise in NCDs in Africa with high age standardized disability adjusted life years (DALYs) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Another Zimbabwean study which used an individual multi-disease model evaluated that between 2015 and 2035, the most prevalent NCDs are chronic kidney injury (CKD), hypertension, depression and cancer with an estimation of 59% of PLHIV having at least one NCD by 2035 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAfrica is facing the highest burden of diabetes mellitus, with Zimbabwe being amongst the countries with a high age standardized death rate of diabetes mellitus among females of 20\u0026ndash;35 per 100000 population (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). African countries have also high prevalence of hypertension ranging from 24\u0026ndash;34% among adults; with 82% of them being neither aware nor on treatment (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). A review on monitoring progress of the African region in achieving national commitments towards NCDs has been slowest (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe risk of contracting NCDs include HIV infection, the ART regimens, aging, physical inactivity, use of tobacco, air pollution, unhealthy diets, dyslipidemia and alcohol abuse (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The response to NCDs is anchored on early detection and screening combined with palliative care and treatment (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The increased burden of the NCDs in Africa demands dependable estimation of the NCDs epidemiology to develop appropriate prevention and control measures (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn high HIV burden settings, multimorbidity has been increasing among the adolescents and younger people with an increased risk of developing HIV related NCDs (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). A South African study reported that initial HIV response is more focused on mothers and children more than in older adults as they are assumed to be at a lower risk which increases the challenges in the management of NCDs and HIV in elderly people (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In Uganda one in five HIV positive people had an NCD in 2018 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe control of the HIV/NCD burden requires the sensitization of the population through some of the HIV programs such as community engagement and defaulter tracing (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The existence of more than one chronic disease in a person has been lacking adequate integrated healthcare which is a major health system challenge (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAt Victoria Chitepo Provincial Hospital (VCPH) an in depth analysis of the burden of NCDs has not been done. The burden of PLHIV developing NCDs has been on the rise globally but this has not been evaluated in the cohort managed at VCPH, which is the referral facility for Manicaland Province. We therefore analyzed the data of NCDs among PLHIV at VCPH from 2013 to 2023.\u003c/p\u003e \u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eResearch Question\u003c/h2\u003e \u003cp\u003eWhat are factors associated with development of NCDs among PLHIV at VCPH over the past ten years?\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eBroad Objective:\u003c/h2\u003e \u003cp\u003eTo determine the risk factors associated with development of NCDs among PLHIV at VCPH from 2013 to 2023.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSpecific Objectives\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo determine the demographic factors associated with development of NCDs among PLHIV at VCPH from 2013 to 2023.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo determine the clinical factors associated with development of NCDs among PLHIV at VCPH from 2013 to 2023.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo determine the prevalence of NCDs among PLHIV by ART regimen at VCPH from 2013 to 2023.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo describe outcomes of HIV/NCDs comorbidity (alive, lost to follow up, dead) among PLHIV at VCPH from 2013 to 2023.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo determine the trends of cumulative NCDs among PLHIV at VCPH from 2013 to 2023.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eA retrospective cohort study of PLHIV initiated on ART from October 2013 to September 2023, using secondary data was carried out.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting\u003c/h2\u003e \u003cp\u003eThe study was conducted at Victoria Chitepo Provincial Hospital (VCPH). VCPH is situated in Mutare City 3.4km north of Mutare town along the Mutare-Harare highway. Mutare is the third biggest city in Zimbabwe (after Harare and Bulawayo) and VCPH is the biggest government hospital in eastern Zimbabwe. VCPH is located in Mutare City which is in Manicaland province. It is a referral hospital for all the seven (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) districts of the province. The hospital serves a population of two million people in the province. By December 2022, 132755 people were on ART, in Manicaland Province (DHIS2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eStudy participants were records of all PLHIV, enrolled on ART with case based data entered into the ePMS and patient booklets at VCPH for the cohorts from 2013 to 2023. Key informants were drawn from health care workers who work in the opportunistic infection department at VCPH.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSample size calculation\u003c/h2\u003e \u003cp\u003eSample size was calculated using the Dobson formula \u003cb\u003en\u0026thinsp;=\u0026thinsp;z\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003ep (1-p)/d\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e, with sensitivity analysis based on a study by Cheza \u003cem\u003eet al\u003c/em\u003e (2019) on incidence of non-communicable diseases in HIV patients on ART in a developing country: Case of Zimbabwe\u0026rsquo;s Chitungwiza central hospital-A retrospective cohort study with a prevalence of 63% on being a female; and in another study by Pangmekeh \u003cem\u003eet al\u003c/em\u003e (2019) on association between highly active antiretroviral therapy (HAART) and hypertension in persons living with HIV/AIDS at the Bamenda regional hospital, Cameroon with a prevalence of hypertension in PLHIV on ART of 36.44% ; at 95% confidence interval, precision (d\u003csup\u003e2\u003c/sup\u003e) of 5% and a non-response rate of 10%. The minimum sample size for the patients\u0026rsquo; records was 394.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eSampling\u003c/h2\u003e \u003cp\u003eTo increase the power of the study; all the 974 records of PLHIV initiated on ART who presented at VCPH from October 2013 to September 2023 were enrolled into the study using ePMS and patient booklets.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eData capture and analysis\u003c/h2\u003e \u003cp\u003eData which was captured from the ePMS and patient booklets which includes the age, sex, follow up status, CD4 count, ART regimen, ART start date, attendance records and the NCDs of the PLHIV. The five major groups of NCDs were selected from the records which are hypertension (HPT), diabetes mellitus (DM), chronic kidney injury (CKD), cancers and respiratory infections. Univariate analysis was performed through the calculation of proportions, means, medians and frequencies. Kaplan Meier analysis was performed using the same software, measuring against the event of interest: development of NCDs. The time to event was measured in months. Risk ratios and hazard ratios with 95% confidence intervals were generated and recorded from analysis. Cleaning of data was done before analysis. The Kaplan Meier and Logrank tests were used for survival analysis of the different groups of NCDs among PLHIV.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEthical considerations\u003c/h2\u003e \u003cp\u003e Permission to carry out the study was obtained from Manicaland Provincial Medical Directorate, Victoria Chitepo provincial hospital and Health Studies Office (HSO). Confidentiality of the patient records and study participants was maintained. No names were included on the key informant guide.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 974 patient booklets were successfully reviewed. The demographic and clinical characteristics are shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Majority of the reviewed records constituted of females 565 (58.0%). Median age of the patients in years was 43 (Q\u003csub\u003e1=\u003c/sub\u003e35; Q\u003csub\u003e3\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;51). Out of the 159 (16.3%) who developed NCDs, 59.1% of them had hypertension.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of HIV/NCD cases, Victoria Chitepo Provincial Hospital, October 2013 \u0026ndash; September 2023\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e409 (42.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e565 (58.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase classification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003cp\u003eCancers\u003c/p\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003cp\u003eRespiratory infections\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94 (9.7)\u003c/p\u003e \u003cp\u003e76 (7.8)\u003c/p\u003e \u003cp\u003e9 ((0.9)\u003c/p\u003e \u003cp\u003e6 (0.6)\u003c/p\u003e \u003cp\u003e3 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003cp\u003eLost to follow up\u003c/p\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e864 (88.7)\u003c/p\u003e \u003cp\u003e87 (8.9)\u003c/p\u003e \u003cp\u003e23 (2.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage 1\u003c/p\u003e \u003cp\u003eStage 2\u003c/p\u003e \u003cp\u003eStage 3\u003c/p\u003e \u003cp\u003eStage 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e400 (41.2)\u003c/p\u003e \u003cp\u003e331 (34.1)\u003c/p\u003e \u003cp\u003e217 (22.3)\u003c/p\u003e \u003cp\u003e24 (2.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge in years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian age (Q\u003csub\u003e1\u003c/sub\u003e; Q\u003csub\u003e3\u003c/sub\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (Q\u003csub\u003e1=\u003c/sub\u003e35;Q\u003csub\u003e3\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeriod of years on ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5 years\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e486 (49.9)\u003c/p\u003e \u003cp\u003e488 (50.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of current regimen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNevirapine based\u003c/p\u003e \u003cp\u003eEfavirenz based\u003c/p\u003e \u003cp\u003eDolutegravir based\u003c/p\u003e \u003cp\u003eProtease inhibitor based\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (8.7)\u003c/p\u003e \u003cp\u003e514 (52.8)\u003c/p\u003e \u003cp\u003e917 (94.2)\u003c/p\u003e \u003cp\u003e54 (5.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn this study, PLHIV who were 40 years or older had 5.41 times risk of developing diabetes mellitus compared to those who were less than 40 years and it was statistically significant p\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Those who were initiated on dolutegravir had 1.12 times risk of developing diabetes mellitus compared to those who did not take dolutegravir and it was not statistically significant p\u0026thinsp;=\u0026thinsp;0.82. PLHIV on WHO stage 3 or 4 (advanced HIV disease) had 2.72 times risk of developing diabetes mellitus compared to those who were on WHO stage 1 or 2. This was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). HIV positive patients who were 40 years or older had 4.81 times risk of developing hypertension compared to those who were less than 40 years and this was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThe probability of developing DM in PLHIV at 40 years and above was higher than in those below 40 years and it was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The probability of developing diabetes mellitus in PLHIV increased with increasing years on ART and it was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The probability of developing diabetes mellitus among PLHIV was not different among DTG users and DTG non-users and it was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.43). The probability of developing diabetes mellitus among PLHIV initiated on EFV based regimen is lower among EFV based regimen users than EFV based regimen non-users and it is statistically significant (p\u0026thinsp;=\u0026thinsp;0.001). The probability of developing diabetes mellitus among PLHIV initiated on PI based regimen is higher among PI based regimen users than PI based regimen non-users and it was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThe probability of developing hypertension among PLHIV increased with increasing number of years on ART and it statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The probability of developing hypertension in PLHIV at 40 years and above was higher than in those below 40 years and it was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The probability of developing hypertension in PLHIV was higher in females than males but it was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.37).\u003c/p\u003e \u003cp\u003eControlling for gender and other variables (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e); the hazard for hypertension was 5.99 times higher in patients who had 5 or more years on ART compared to those who were on ART for less than 5 years and it was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Other hazards were being 40 years and above and being diabetic. There was approximately 53% lower risk of developing hypertension in the patients on efavirenz based regimen compared to non-users of efavirenz based regimen.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCox proportional hazards for development of hypertension\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eART period (\u0026ge;\u0026thinsp;5, \u0026lt;\u0026thinsp;5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge group (\u0026ge;\u0026thinsp;40, \u0026lt;\u0026thinsp;40)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiagnosed DM (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWHO stage (3 or 4, 1 or 2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNVP based (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePI based (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDTG based (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEFV based (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex (male, female)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe risk of developing DM was 9.89 times higher in patients who had 5 or more years on ART compared to those who had less than 5 years and this was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The other hazards to development of DM were being on PI based regimen, being greater than 40 years, being at WHO stage 3 or 4 and having hypertension. The hazard for diabetes mellitus was less for nevirapine based and efavirenz based regimens. However, there was no statistical significance between dolutegravir use and development of DM (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCox proportional hazards for development of diabetes mellitus\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eART period (\u0026ge;\u0026thinsp;5,\u0026lt;5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePI based (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge group (\u0026ge;\u0026thinsp;40,\u0026lt;40)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWHO stage (3 or 4, 1 or 2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiagnosed of HPT (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDTG (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEFV based (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNVP based (yes, no)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex (male, female)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMajority of PLHIV in this study had hypertension 94 (9.7%) and diabetes mellitus 76 (7.8). In our study, with total records reviewed of PLHIV of 974 and 159 NCDs, the prevalence rate was approximately 17 per 100 people per year in Manicaland province. A total of 6 (0.6%) PLHIV died from HPT/HIV comorbidity, 7 (0.7%) from DM/HIV comorbidity, 1 (0.1%) from cervical cancer/HIV comorbidity and 1 (0.1%) from CKD/HIV comorbidity in this cohort. A total of 15 NCD/HIV deaths out of the 159 PLHIV who developed NCDs gave an approximate case fatality rate of 1 per 10 PLHIV with NCDs per year.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe highest NCD among PLHIV in this cohort was hypertension (HPT). This hypertension results from prothrombotic changes and inflammation caused by HIV as evidenced by Chastain et al (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Aging in PLHIV was directly associated with development of hypertension as the exposure to HIV also increased. Similarly, Chastain et al and Daniel et al evidenced that the time on ART, the various types of regimens and the duration of HIV diagnosis have been associated with hypertension (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe survival of PLHIV with HPT/HIV comorbidity reduced with age as they deteriorated more over time with aging and immunosuppression thereby shortening their lifespan. Similarly, in another study in Poland, the increase in duration with HIV disease and aging has been directly associated with CVD risk (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). As PLHIV were mostly screened on the yearly routine hospital visit, it delayed the diagnosis and treatment of the hypertension among other NCDs. Delayed diagnosis and treatment of hypertension can be linked to the high morbidity and mortality among these PLHIV as previously evidenced in an American study (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA high case fatality rate was evidenced in diabetics in this retrospective cohort study compared to other NCDs. Management of both type 1 and type 2 diabetes mellitus can be critical as they both depend on the dietary and exercise lifestyle other than medication. Moreover, the risk of developing diabetes mellitus increased with age and years on ART from our study. A previous study in Iran by Hadavandsiri et al supported that glucose tolerance impairment increased with age (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). However, Bujuma et al also evidenced that exposure to ART and increasing years on ART was significantly associated with development of diabetes mellitus. In contrary, PLHIV on efavirenz or nevirapine in our study had higher chances of survival from developing diabetes mellitus compared to those on other regimens. This could be due to the lower influence on metabolic syndrome of non-nucleoside reverse transcriptase inhibitors (NNRTI) compared to other ART classes leading to reduced risk of hyperglycemia, dyslipidemia and hypertension related, as previously evidenced by Nguyen et al (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWHO stage 3 or 4 also increased the risk of developing diabetes mellitus due to the HIV immunocompromised state. Switching of regimens is thereby recommended to monitor glucose metabolism (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). The potential risk of developing hyperglycemia due to various ART switches and HIV metabolic syndrome reduced the survival of PLHIV as evidenced in our study. In contrary to our study findings, patients who were on WHO stage 1 had higher risk of developing diabetes mellitus compared to other clinical stages in an Ethiopian study (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). However, in another study in Kenya, WHO staging had no significant association with development of NCDs (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe immune suppression due to cervical cancer/HIV comorbidity resulted in death of one of the PLHIV in the study. We have noted a low number of cancer/NCD cases in this cohort and this has also been reported by Cheza et al in Zimbabwe that cancers have the lowest incidence rate compared to other NCDs (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Early cervical cancer screening and the human papilloma virus vaccine reduced the cancer incidence thereby reducing the cervical cancer/HIV related mortality (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur study had an HIV positive patient who also suffered chronic kidney disease and died. This could be attributed to poorly controlled HIV and exposure to other ART regimens which causes cytopathic effect to the glomerular filtration leading to renal failure as supported by Alfano et al, Naicker et al and other researchers (\u003cspan additionalcitationids=\"CR32 CR33\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough our study reported the least number of PLHIV with respiratory illnesses such as asthma, all of them were in WHO stage 3 in ART initiation which is characterized by HIV/AIDS due to the weakened immunity. The use of ART has been evidenced to reduce respiratory infections/HIV related mortality (\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDolutegravir has been hypothesized to cause insulin resistance through the chelation of its cofactor, the magnesium ions, thereby increasing the risk of hyperglycemia. However, our study evidenced that there was no statistical significance between DTG use and development of diabetes mellitus. DTG was combined with other regimens giving better cardio metabolic profile, with DTG associated with high viral load suppression and the other regimens in the combination controlling metabolism. Moreover, our study constituted a 94% coverage of DTG users which could make the non-diabetic DTG users override the diabetic DTG users in analysis. Supporting evidence of using combined regimens to control metabolism has been reported by Tripathi et al (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eProtease inhibitor based regimen was a hazard to diabetes mellitus in this study group. This follows as PI based regimens produce enzymes that catalyze human proteins involved in homeostasis, metabolism and cell growth thereby inducing impaired glucose tolerance (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). This increases the risk of developing hyperglycemia. Hughes et al also evidenced that longer duration on protease inhibitors increased the risk of developing diabetes mellitus (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, one in five PLHIV had an NCD. Similarly, in Uganda one in five HIV positive people had an NCD (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The similar study findings could be due to similar country policies which are against gays and lesbians. Moreover, the economic settings in Zimbabwe and Uganda are similar as both are low resource settings. In Zimbabwe, just like other Sub-Saharan Africa countries; multimorbidity has been increasing among the adolescents and younger people with an increased risk of developing HIV related NCDs (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOn updating the patient booklets, some of the files were disposed with information of interest such as previous ART history and patients who deceased five or more years ago, thereby eliminating some PLHIV from the cohort study. Some patients who were lost to follow up and could not be determined their interval when they were out of the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eRecommendations and conclusion\u003c/h2\u003e \u003cp\u003eHypertension and diabetes mellitus are the common NCDs among PLHIV due to the metabolic syndrome from HIV and the various ART regimens, causing high morbidity and mortality in this cohort. To minimise complications related to these NCD/HIV comorbidities, we recommend routine screening of NCDs at monthly basis for early diagnosis and treatment.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests both financial and non-financial.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthors\u0026rsquo; contributions KC: conception, design, acquisition, analysis and interpretation of data and drafting the manuscript. MM: conception, design, acquisition, analysis and interpretation of data and drafting the manuscript. TJ: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. AC: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. GS: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. NG: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. MT: conception, design, data collection, analysis, interpretation and reviewing of several drafts of the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThe authors acknowledge the Manicaland Provincial Medical Directorate for their support in conducting this study. The authors are also thankful to the Zimbabwe MPH-FETP program and Centers for Disease Control and Prevention (CDC) Zimbabwe for technical assistance.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData availability statement\"The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\"\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGeorge S, McGrath N, Oni T. The association between a detectable HIV viral load and non-communicable diseases comorbidity in HIV positive adults on antiretroviral therapy in Western Cape, South Africa. BMC Infectious Diseases. 2019 Apr 27;19(1):348. \u003c/li\u003e\n\u003cli\u003eNCD Alliance [Internet]. 2012 [cited 2023 Feb 16]. The HIV experience and other chronic diseases-UNAIDs and WHO Partnership on NCDs. 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PLoS ONE. 2016 Mar 23;11(3):e0150970. \u003c/li\u003e\n\u003cli\u003eNamara D, Schwartz JI, Tusubira AK, McFarland W, Birungi C, Semitala FC, et al. The risk of hyperglycemia associated with use of dolutegravir among adults living with HIV in Kampala, Uganda: A case-control study. Int J STD AIDS. 2022 Dec 1;33(14):1158\u0026ndash;64. \u003c/li\u003e\n\u003cli\u003eLamorde M, Atwiine M, Owarwo NC, Ddungu A, Laker EO, Mubiru F, et al. Dolutegravir-associated hyperglycaemia in patients with HIV. The Lancet HIV. 2020 Jul;7(7):e461\u0026ndash;2. \u003c/li\u003e\n\u003cli\u003eWayback Machine [Internet]. 2020 [cited 2023 Sep 5]. Available from: https://web.archive.org/web/20201124104826/https://www.dovepress.com/front_end/cr_data/cache/pdf/download_1606214533_5fbce385d8996/hiv-279732-diabetes-mellitus-and-associated-factors-among-adult-hiv-(1).pdf\u003c/li\u003e\n\u003cli\u003eAchwoka D, Waruru A, Chen TH, Masamaro K, Ngugi E, Kimani M, et al. Noncommunicable disease burden among HIV patients in care: a national retrospective longitudinal analysis of HIV-treatment outcomes in Kenya, 2003-2013. BMC Public Health. 2019 Apr 3;19(1):372. \u003c/li\u003e\n\u003cli\u003eSiegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023;73(1):17\u0026ndash;48. \u003c/li\u003e\n\u003cli\u003eHIV and Kidney Disease | NIH [Internet]. [cited 2023 Sep 7]. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-kidney-disease\u003c/li\u003e\n\u003cli\u003eAlfano G, Cappelli G, Fontana F, Di Lullo L, Di Iorio B, Bellasi A, et al. Kidney Disease in HIV Infection. JCM. 2019 Aug 19;8(8):1254. \u003c/li\u003e\n\u003cli\u003eNaicker S, Rahmania S, Kopp JB. HIV and chronic kidney disease. Clin Nephrol. 2015 Mar;83(Suppl 1):S32\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eUe E, Ap K, Ak B, Ee E, Jj N, Bl S, et al. 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Available from: https://pubmed.ncbi.nlm.nih.gov/23422413/\u003c/li\u003e\n\u003cli\u003eIncidence of diabetes mellitus in a population-based cohort of HIV-infected and non-HIV-infected persons: the impact of clinical and therapeutic factors over time. - Abstract - Europe PMC [Internet]. [cited 2023 Sep 5]. Available from: https://europepmc.org/article/MED/24673640\u003c/li\u003e\n\u003cli\u003eRavindra PV, Girish TK. Role of Proteases in Diabetes and Diabetic Complications. In: Chakraborti S, Dhalla NS, editors. Proteases in Physiology and Pathology [Internet]. Singapore: Springer; 2017 [cited 2023 Dec 6]. p. 289\u0026ndash;96. Available from: https://doi.org/10.1007/978-981-10-2513-6_13\u003c/li\u003e\n\u003cli\u003eLien LF, Feinglos MN. Protease Inhibitor-Induced Diabetic Complications. Drug-Safety. 2005 Mar 1;28(3):209\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eHughes CA, Cashin RP, Eurich DT, Houston S. Risk factors for new-onset diabetes mellitus in patients receiving protease inhibitor therapy. Can J Infect Dis Med Microbiol. 2005;16(4):230\u0026ndash;2. \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":"Non-communicable disease, Human immunodeficiency virus, ART, Manicaland province","lastPublishedDoi":"10.21203/rs.3.rs-4711585/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4711585/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eNon-communicable diseases (NCDs) associated with human immunodeficiency virus (HIV) are emerging as the leading cause of death globally. An in depth analysis of the burden of NCDs in Manicaland province has not been done. We analyzed the NCDs/HIV data at Victoria Chitepo provincial hospital.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study from October 2013 to September 2023 using secondary data. Five major groups of NCDs were selected which were hypertension (HPT), diabetes mellitus (DM), chronic kidney injury (CKD), cancers and chronic respiratory illness. Kaplan Meier analysis and Cox proportional hazard analysis were performed. Risk ratios and hazard ratios with 95% confidence intervals were generated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 974 patient records were reviewed with a median age of 43 (Q\u003csub\u003e1=\u003c/sub\u003e35; Q\u003csub\u003e3\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;51) years. Number of years on antiretroviral therapy (ART) (HR\u0026thinsp;=\u0026thinsp;5.99, 95% CI: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), age (HR\u0026thinsp;=\u0026thinsp;4.78, 95%CI: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DM/HIV comorbidity (HR\u0026thinsp;=\u0026thinsp;4.63, 95% CI: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were hazards to HPT while being on efavirenz based regimen had a lower risk (HR\u0026thinsp;=\u0026thinsp;0.47, 95% CI: p\u0026thinsp;=\u0026thinsp;0.01) of developing HPT. Number of years on ART (HR\u0026thinsp;=\u0026thinsp;9.89, 95% CI: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), being on PI based regimen (HR\u0026thinsp;=\u0026thinsp;4.66, 95% CI: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), age (HR\u0026thinsp;=\u0026thinsp;3.86, 95% CI, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and being on WHO stage 3 or 4 (HR\u0026thinsp;=\u0026thinsp;3.75, 95% CI: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were hazards to DM. In 2022, the prevalence rate was 12 per 1000 people per year.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eHPT and DM are the common NCDs among people living with HIV in this cohort. To minimize complications related to NCD/HIV comorbidities, we recommend routine screening of NCDs at monthly basis for early diagnosis and treatment.\u003c/p\u003e","manuscriptTitle":"Non-communicable diseases among people living with HIV, Victoria Chitepo provincial hospital: A retrospective cohort study, a secondary data analysis (2013-2023)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 11:27:30","doi":"10.21203/rs.3.rs-4711585/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":"fc57663c-2b32-4775-bbd3-2b4b1d532087","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-17T14:23:58+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-26 11:27:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4711585","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4711585","identity":"rs-4711585","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}