Incidence and Predictors of Treatment Failure Among Children Receiving First-Line Antiretroviral Therapy in East Gojjam, Ethiopia: A Fifteen-year Retrospective Cohort Study

Incidence and Predictors of Treatment Failure Among Children Receiving First-Line Antiretroviral Therapy in East Gojjam, Ethiopia: A Fifteen-year Retrospective Cohort 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 Incidence and Predictors of Treatment Failure Among Children Receiving First-Line Antiretroviral Therapy in East Gojjam, Ethiopia: A Fifteen-year Retrospective Cohort Study Abere Kassie, Makonnen Adimasu, Erdaw Tachbele This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3887288/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 Human immunodeficiency virus (HIV) infection is still a major health problem in children in Ethiopia. Even though there is a rapid scale-up of antiretroviral therapy (ART), information on pediatric treatment failure is limited in the country. Hence, this study was designed to assess the incidence and predictors of ART treatment failure among children who were receiving first-line ART in East Gojjam, Ethiopia. Methods A fifteen-year retrospective follow-up study was conducted among 538 randomly selected under-15-year-old children who started antiretroviral medication between September 11, 2006, and September 10, 2021, in multicentre health facilities in East Gojjam. The medical records of the study participants were reviewed, and the required data were extracted using pretested structured checklists. The data were entered and cleaned using SPSS version 25 and exported to STATA version 14 for further statistical analysis. The Kaplan‒Meier survival curve, the log-rank test, and the scaled Schoenfeld residual test were applied for analysis. Results From a total of 538 medical records of children receiving antiretroviral treatment reviewed, 114 (21.2%) (95% CI: 17.8–24.9) developed treatment failure, 85 (74.6%) were virological, 19 (16.7%) were immunological (CD4), and 10 (8.8%) were clinical failures. The overall incidence density of treatment failure was 4.53 per 1000 person-months, with a mean survival time of 43.8 months (95% CI = 37.65–50.89) at treatment failure. WHO clinical stage III/IV (AHR = 3.0, CI = 1.3, 7.1), regimen not changed (AHR = 4.4, CI = 1.7, 11.7), poor ART adherence (AHR = 6.6, CI = 4.11, 10.66), stunting (AHR = 2.2, CI = 1.43, 3.44), and nevirapine containing regimen (AHR = 2.72, CI = 1.13–6.54) were significant predictors of treatment failure. Conclusion The incidence of ART treatment failure among the study participants was significantly high. WHO clinical stage III/IV, poor adherence to ART, regimen not changed, and nevirapine-containing regimen were all significant predictors of ART failure. Hence, by providing intensive care and close monitoring to higher-risk patients, a timely change in regimen was recommended. Incidence Predictors ART treatment failure Ethiopia Figures Figure 1 Introduction At the end of 2021, 38.4 million people were living with HIV worldwide. A total of 1.7 million were children, and 110,000 of them died due to HIV-related illnesses in the same year [ 1 ]. In Ethiopia, a total of 612,925 HIV patients were living, 41,788 of whom were children at the end of 2021[ 2 ]. Although ART significantly improves the quality of life of PLWH, treatment failure is associated with a high risk of mortality following the start of ART. ART failure in children is classified as virologic, immunologic, clinical failure, or a combination of the three[ 3 ]. HIV-infected children are more vulnerable to negative outcomes, including death, if there is no life-saving ART and regular medical supervision [ 4 – 6 ]. Even if pediatric ART coverage increases, more children than adults develop treatment failure because they rely on their parents or caregivers to obtain healthcare services[ 7 ]. Pediatric ART failure rates range from 19.3% to more than 32.0% in resource-limited settings[ 8 ]. Studies conducted in several African countries have reported that the prevalence of pediatric ART failure ranges from 15–57%[ 9 – 14 ]. In a recent meta-analysis, the pooled prevalence of treatment failure among children in Ethiopia was 12.34% [ 10 ]. Studies conducted in different African countries, including Ethiopia, have indicated that poor ART adherence, advanced WHO clinical staging, and opportunistic infections are significant predictors of childhood treatment failure[ 10 – 12 , 15 ]. Childhood ART failure was also found to be associated with the baseline regimen and changes in the regimen. According to studies conducted in Ethiopia and Tanzania, children who received nevirapine (NVP)-based treatment regimens were two times more likely than those who received efavirenz and protease inhibitor-based treatment regimens to experience treatment failure[ 12 , 16 ] There is limited information on the rate and determinants of ART failure among children in the current study area, particularly after the initiation of the new ART guide line in 2019 in Ethiopia. Hence, this study was designed to determine the incidence rate and predictors of ART failure among children in public health facilities in East Gojjam, Ethiopia.2021 Methods Study design, period and setting A multicenter facility-based retrospective follow-up study was conducted from September 11,2006 to September 10, 2021 to assess the incidence of treatment failure and its predictors at public health facilities in the East Gojjam Zone. The zone is located 300 kilometers from Addis Ababa, the capital of Ethiopia, and has a total population of 2,719,118 and 632,353 households. The Zone has 423 health posts, 102 health centers, 9 primary hospitals, one general hospital, and one referral hospital. Of these, only 34 health institutes provided ART services for a total of 903 HIV-positive children in 2021; 11 health facilities (5 hospitals and 6 health centers) were randomly selected as study sites. Specifically, Debre-Markos Referral Hospital, Shegaw Motta General Hospital, Lumame Primary Hospital, Bichena Primary Hospital, Mertule Mariam Primary Hospital, Debre Markos Health Center, Dejen Health Center, Mertule Mariam Health Center, Lumame Health Center, Bichena Health Center, and Amber Health Center were included as study sites. Study population All HIV-positive children under the age of 15 who started ART at East Gojjam Zone Public Health Institutions composed the study population. Children who started ART between September 2006 and September 2021 and who had taken ART for at least six months were included in the study. Children with incomplete admission information, such as age, type of caregiver, address, sex, CD4 count, hemoglobin level, ART beginning time, and who were on ART for less than six months, were excluded. Sample size determination and sampling procedure The sample size was calculated using the Epi Info version 7 software's double population proportion difference formula, taking into account severe underweight, severe wasting, hemoglobin < 10 g/dl, CD4 count or % below the threshold and WHO clinical stage III/IV from previously conducted studies[ 17 , 18 ]. The final and maximum sample size, 558 individual charts, was provided by the sample size that we calculated based on the CD4 count or percentage below the threshold, considering the following assumptions: a percentage of exposed (26%) and nonexposed (16%), a ratio of one to one exposed to nonexposed (1:1), a 95% confidence level, a 1.63 hazard ratio, and 80% power. Medical records were arranged for all 903 children under 15 years of age who began ART between September 11, 2006, and September 10, 2021, at the 11 selected health facilities. Following a proportionate allocation of the 558 study participants to each study site, data were extracted using a basic random sample approach from the records of each enrolled child over a period of 15 years. Variables The incidence rate of ART failure and time to ART failure were the dependent variables. The independent variables were sociodemographic, laboratory and clinical characteristics. In addition, sociodemographic variables of parents/caregivers, including residence, marital status, occupation, age, sex and HIV serostatus, were included. Furthermore, WHO clinical stage, CD4 count, hemoglobin level, functional status (for ≥ 5 years), developmental status (for < 5 years), opportunistic infection, prophylaxis therapy (CPT and INH), duration of ART treatment, type of ART regimen, pharmacological adverse effects, adherence to ART, and nutritional status (wasting, stunting, underweight and BMI for age) were considered predictor variables. Data collection tool The standardized ART entry and follow-up formats of the Ministry of Health were utilized to develop the data extraction tools. The data were collected from children's charts and electronic databases by data collectors using the developed data extraction sheet. Data quality control The information was gathered by eleven nurses who had been trained in comprehensive HIV care and were involved in patient follow-up. A pretest was conducted on 10% of the sample at Debre Work Primary Hospital. Both the data collectors and supervisors received a one-day training session on the data collection tool and procedures. The data quality was also ensured by using the right data gathering instrument and maintaining constant oversight. Checklists were assigned codes. Every day, the data collectors and supervisors examined all the obtained data for completeness. Data processing and analysis The collected data were checked for completeness and consistency and then coded and recorded in SPSS version 25. The data were subsequently cleaned and analysed using STATA version 14. Descriptive statistics were computed to determine frequencies and summary statistics (mean, standard deviation and percentage). WHO AnthroPlus version 1.04 software was used to generate Z scores (WAZ, HAZ and WHZ/BIAZ) to determine nutritional status. The Kaplan–Meier survival curve was used to estimate the time to develop treatment failure after the initiation of antiretroviral therapy. Log rank tests were applied to compare survival curves of categorical predictor variables. To determine the effect of the predictors on the duration of ART failure, a bivariable Cox regression proportional hazard model was fitted for each explanatory variable. Finally, those variables with p values < = 0.25 in the bivariant analysis were fitted to the multivariable Cox proportional hazard regression model. The hazard ratio (HR) with a 95% confidence interval (CI) and p value were used to predict the strength of the association and identify statistically significant results. A P value < 0.05 was considered to indicate a statistically significant association. The Cox proportional hazard model assumption was confirmed using the scaled Schoenfeld residual test (a P value greater than 0.05 met the assumption) and graphically with the log-log Cox adjusted survival estimate. The fitness of the model was checked using the Cox–Snell residual test. Operational definitions In this study, “event” was considered the time to treatment failure, treatment failure, and its predicters. Censoring was other than the event (transfer outs, defaulters, deaths, patients who did not develop treatment failure during the study period, or switchers due to factors other than first-line ART failure). The time to occurrence of an event or censored cases was measured in months. Disclosure : is defined as when the child knows his/her HIV and treatment status irrespective of the source. Duration of ART : the time between the start date of ART and the last contact date with the health facility during data collection. Undernutrition : If the child has one height/age<-2, weight/age<-2, weight/height <-2 or BMI for age <-2 standard deviations according to the WHO curve. The functional status was defined as working (playing, doing normal activities, and going to school), ambulatory (able to perform daily living activities), or bedridden (not able to perform daily living activities) (23). Adherence : taking the right ARV medication at the right dose at the right time every day and exactly as long as they were prescribed for life. were classified as follows: good if adherence was ≥ 95% (1 dose of 30 doses or 2 doses of 60 dose missed), fair if adherence was between 85 and 94% (2 and 4 doses of 30 dose or 4 and 9 doses of 60 dose were missed), and poor if adherence was < 85% (≥ 5 dose of 30 dose or ≥ 10 dose of 60 dose was missed) [ 19 ]. Developmental status was defined as appropriate (if a child has reached a milestone for age), delay (if the child fails to reach a milestone for age) or regression (loss of appropriate developmental milestones due to illness) [ 19 ]. Results Sociodemographic characteristics of children on ART A total of 538 (96.4%) records of children with HIV were included in the final analysis. Of these, 285 (53.0%) were males, the mean age was 7.25 (95% CI = 6.95–7.58) years, and 398 (74%) of the children were older than five years. The majority 389 ( 72.3%) were urban residents, 378 (70.3%) were living with their parents, and almost half were living with their parents; 274 (50.9%) were alive mothers and fathers (Table 1 ). Table 1 Sociodemographic characteristics of children on ART at East Gojjam Zone public health facilities, North West Ethiopia, 2006–2021 (n = 538) Variable Category Frequency Percent Sex of children Male 285 53.0 Female 253 47.0 Age of children ≥ 5 years 398 74.0 < years 128 23.8 < 1 years 12 2.2 Relation of child to care giver Parent 378 70.3 Uncle/aunt 22 4.1 Sister/brother 29 5.4 Grand parent 35 6.5 Guardian 73 13.6 Religion of parent/care giver Muslim 26 4.9 Orthodox 452 85.4 Residence Urban 389 72.3 Rural 149 27.7 Marital status of caregiver Married 318 59.1 Single 38 7.1 Widowed 118 21.9 Divorced 64 11.9 HIV status of parent/caregiver Both positive 163 30.3 Mother positive 266 49.4 Father positive 32 5.9 Father negative 9 1.7 Unknown 42 7.8 Parent status Both alive 274 50.9 Only mother alive 83 15.4 Only father alive 49 9.1 Both died 130 24.2 Un known 2 0.4 Clinical, laboratory, and ART baseline characteristics At the time of ART initiation, 318 children (59.1%) had opportunistic infections. The mean and median haemoglobin levels were 12.059 mg/dl and 12.2 mg/dl (95% CI = 11.901, 12.217), respectively. In terms of WHO clinical stage, 281 (52.2%) patients were in stage I or stage II, and 73.7% of the children who were enrolled in ART had a viral load lower than 1000 copies/ml at baseline. With respect to developmental status, 383 (71.1%) were appropriate for their age. At the time of ART initiation, 391 (72.7%) children’s CD4 count was below the threshold. A total of 197 (36.6%) of the study participants were eligible for ART treatment due to a low CD4 count (Table 2 ). Table 2 Baseline clinical and immunological characteristics of children on first-line ART in East Gojjam Zone Public Health Facilities, Ethiopia, 2006–2021 (n = 538) Variable Category Frequency Percent Opportunistic infections Yes 318 59.1 No 220 40.9 Types of opportunistic infections Diarrhea 65 20.4 Candidiasis 53 16.7 Pneumonia 54 17.0 Tuberculosis 65 20.4 Skin Rash 53 16.7 Herpes Zoster 28 8.8 Functional status ≥ 5 years (N = 398) Working 207 52 Ambulatory 168 42.2 Bed ridden 23 5.8 Developmental status < 5 years (N = 140) Appropriate 100 71.4 Delayed 36 25.7 Regressed 4 2.9 WHO staging Stage I/II 281 52.2 Stage III/IV 257 47.8 Hemoglobin level ≥ 10 mg/dl 269 50 < 10 mg/dl 269 50 CD4 count Above thresh hold 150 27.9% Below thresh hold 388 72.1% Viral load < 1000 copies/mL 315 58.6 ≥ 1000 copies/mL 223 41.4 ART eligibility criteria WHO staging 70 13 CD4 count 197 36.6 Both clinical and CD4 190 35.3 Test and treat all 81 15.1 Follow-up data on factors related to ART and other medications among the study participants The most common baseline regimen was 4c (AZT-3TC-NVP), which was utilized by 45.5% of the patients, followed by 4a (d4t-3TC-NVP), which was used by 22.5%, and the majority of the patients (393 [73.0%]) were on a nevirapine-based regimen. The great majority of children (92.6%) received prophylaxis, 93% of whom were on CPT. During the study period, only 108 (20.1%) patients changed their regimen, mainly because of drug stocking out 31 (28.7%), and 364 (64.3%) patients were found to have poor treatment adherence. Regarding the nutritional status of the study participants, 86 (16.0%) had stunted growth. Among those under five years of age, 94 (17.5%), 125 (23.2%), and 86 (16.0%) were wasting, underweight, and stunted, respectively (Table 3 ). Table 3 Follow-up data on factors related to ART and other medications among children on first-line ART in East Gojjam Zone Public Health Facilities, Ethiopia, 2006–2021 (n = 538) Variable Category Frequency Percent Baseline regimen 4a(d4t-3TC-NVP) 121 22.5 4b (d4t-3TC-EFV) 37 6.9 4c (AZT-3TC-NVP) 245 45.5 4d (AZT-3TC-EFV) 66 12.3 1e (TDF-3TC-EFV) 13 2.4 1 (ABC-3TC-NVP) 27 5.0 1g(ABC-3TC-EFV) 11 2.0 Other (1c,4i,4j,4g) 18 3.3 Regimen type Nevirapine based regimen 393 73.0 None nevirapine based regimen 145 27.0 Taking prophylaxis Yes 498 92.6 No 40 7.4 Type of prophylaxis CPT 478 96.0 INH 15 3.0 Both CPT and INH 5 1.0 Side effect Yes 24 4.5 No 514 95.5 Type of side effect Anemia 10 41.7 Toxicity 9 37.5 Skin Rash 5 20.8 Regimen change No 430 79.9 Yes 108 20.1 Reason for drug change Drug side effect 15 13.9 Opportunistic infection 20 18.5 Treatment failure 17 15.7 Drug stock out 31 28.7 Drug optimization 25 23.2 Adherence Good 149 27.7 Fair 43 8.0 Poor 346 64.3 Survey end point Alive 348 64.7 Dead 31 5.8 Lost to follow -up 5 0.9 Transferred out 134 24.9 Drop out 20 3.7 First line Treatment Failure Yes 114 21.2 No 424 78.8 Types of Treatment Failure Virological 85 74.5 Immunological 19 16.7 Clinical 10 8.8 Weight for height/length (< 5 year) Normal 444 82.5 Wasted 94 17.5 Weigh for age (< 5 year) Normal 413 76.8 Under weight 125 23.2 Height for age (< 5 year) Normal 452 84.0 Stunted 86 16.0 Weight for age (age < 10 years Normal 409 76 .0 Under weight 129 24. 0 Body mass index for age (≥ 5 year) Normal weight 452 84.0 Thinness 86 16 .0 Height/length for age (< 15 years) Normal 445 82.8 Stunted 93 17.2 Incidence and survival status of treatment failure In this study, 538 participants were followed for a total of 15 years, with a minimum of 6 months and a maximum of 180 months, resulting in 81,295 child-months of observation risk, with a mean and median follow-up of 43.6 and 37 months, respectively. Of the 538 participants, 114 (21.2%) had treatment failures (cases), and 424 (78.8%) were censored. Of those who were censored, 342 (63.6%) participants were alive, 137 (25.5%) were transferred out, 34 (6.3%) died, 20 (3.7%) dropped out, and 5 (0.9%) were lost to follow-up. Among the treatment failures, 85 (74.6%) were virological, 19 (16.7%) were immunological, and 10 (8.8%) were clinical failures (Table 3 ). The cumulative incidence of treatment failure was 21% (95% CI: 17.7–24.7), and the overall treatment failure incidence density rate (IDR) in the study was 4.53 per 1000 person-months. The cumulative probabilities of failure at the end of the 7th, 24th, and 4th months were 7% and 4.4%, respectively. This study showed that the highest incidence of TF occurred between 108–109, 10–11, and 24–25 months after starting ART. As the length of survival increased, the hazard of time to TF increased (Fig. 1 ). Bivariate and multivariate Cox proportional hazard analyses According to our bivariate analysis, children who were WHO clinical stage III/IV had shorter survival than did those with WHO clinical stage I/II. The mean survival time was 52.4 months (95% CI = 41.70, 63.08) for WHO stage I/II and 38.7 months (95% CI = 30.66, 48.82) for WHO stage III/IV (P value = 0.04). Children with stunted nutritional status had shorter survival times than did those with normal nutritional status, with mean and median survival times of 36.3 months (95% CI = 29.292, 43.216) and 31.0 months (95% CI = 19.603, 42.397), respectively, versus 51.7 months (95% CI = 41.004, 62.340) and 44.0 months (95% CI = 35.609, 52.391) (p value = 0.012). Participants with poor adherence to ART had shorter survival times than did those with fair and good adherence to ART, and children with fair adherence to ART had shorter survival times than did those with good adherence, with mean survival times of 26.2 months (CI = 18.974, 33.407) and 46.2 months (CI = 28.983, 63.462) and a median survival time of 48.6 months (CI = 40.063, 57.205) respectively (p. value = 0.003). In the present study, children whose regimen was not changed had shorter survival times than did those whose regimen was changed, with mean survival times of 36.5 (CI = 29.904, 43.106) and 50.7 (CI = 40.112, 61.265) months, respectively (p value = 0.019). In the present study, prolonging the initial regimen was more hazardous for treatment failure than counterpart. The mean duration of treatment with the initial regimen was 42.1 months. Children who received the nevirapine-based regimen had a shorter survival time (mean 39.2 months) at treatment failure than did those who did not (mean 44.2 months) (P value = 0.043). Based on the new WHO 2019 recommendations for antiretroviral treatment, global community identified a new formulation of the fixed-dose combination (FDC) of tenofovir (TDF) 300 mg + lamivudine (3TC) 300 mg + dolutegravir (DTG) 50 mg (TLD) for all eligible adults, adolescents and children aged > 10 years and weighing 35 kg or more (WHO, 2018). Accordingly, the incidences of treatment failure among the study participants before and after the new WHO guidelines were 73 (64%) and 41 (36%), respectively. The hazard of treatment failure in the old regimen was 1.5 times greater than that in the new regimen (CI = 1.021, 2.273) (p = 0.039). Predicators of ART treatment failure A Cox proportional hazard regression model was used to examine any associations between baseline factors and the probability of ART failure in children on ART. The child's sex, baseline viral load, OI before and during the follow-up period, disclosure status, baseline regimen, duration of ART, use of prophylaxis, CD4 count, WHO clinical stage, adherence level, height for age, baseline regimen, and implemented treatment guidelines were all eligible for multivariate Cox regression analysis in the bivariate analysis. However, only WHO stage, ART adherence, height for age, regimen change, baseline regimen, and guideline utilized were found to be significant predictors of ART failure in the multivariate analysis (Table 4 ). The incidence of ART failure was 3 times greater in children with WHO stage III or IV disease than in children with WHO stage I or II disease (AHR = 3.0 CI = 1.3, 7.1). Regarding treatment adherence, children with poor adherence to ART treatment had a 6.6 times greater risk of treatment failure than did their counterparts (AHR = 6.6, CI = 4.11, 10.66). Furthermore, compared to children who had good adherence to ART, those who had fair adherence were 2.2 times more likely to have treatment failure. In addition, the risk of ART failure was 2.2 times greater in stunted children (HFA-2 Z score) than in their peers (AHR = 2.2, CI = 1.43, 3.44). Regarding regimen changes, children whose regimen was not changed were 4.4 times more hazardous for ART failure than for those whose regimen was changed (AHR 4.4, CI = 1.7, 11.7). Children treated according to the previous treatment guidelines were 1.5 times more likely to experience ART failure than were those treated according to the new treatment guidelines (AHR = 1.5, CI = 1.20, 2.273). Similarly, children who received the nevirapine-based regimen were 2.72 times more likely to experience ART treatment failure than children who received the non-nevirapine treatment regimen were (Table 4 ). Table 4: Cox regression analysis of predictors of ART failure among children on ART in East Gojjam Zone public health facilities, Northwestern Ethiopia, 2022. Variables Survival status AHR (95%CI) TF, N (%) Censored, N (%) Age <1yer 1-5 year ≥5 years 3(2.63) 30(26.3) 81(71.1) 9(2.1) 97(22.9) 318(75) 1 1.2 (0.388, 3.924) 0.677(0.443,1.034) Residence Urban Rural 83(72.8) 31(27.2) 306(72.2) 118(27.8) 1 0.679 (0.443, 1.041) OI during follow up Yes No 100(87.7) 14(12.3) 218(51.4) 206(48.6) 2.5 (1.0, 6.0) 1 WHO clinical staging Stage I and II Stage III and IV 24(21.0) 90(79.0) 168(39.6) 256 (60.4) 1 3.0 (1.3, 7.1) * CD4 count or percent Below the threshold Above the threshold 51(44.7) 63(53.30 337(79.5) 87(20.5) 4.4 (1.7, 11.7) 1 Hemoglobin level <10 g/dl ≥10 g/dl 87(76.3) 27(23.7) 182(42.9) 242(50.1) 3.1 (1.4, 6.7) 1 Change of regimen Yes No 15(13.2) 62(86.8) 289(68.2) 135(31.8) 1 4.4 (1.7, 11.7) * Adherence Good Fair Poor 75(65.8) 18 (15.8) 21(18.4) 74(17.5) 25(5.9) 325(76.7) 1 2.2(1.13,4.20) 6.6(4.11,10.66) * Underweight Normal Moderate (WAZ <- 2 Severely (WAZ < -3) 68 (59.6) 50(43.9) 33(28.5) 278(65.6) 65(15.3) 96(22.6) 1 2.0 (0.8, 4.7) 1.2 (0.4, 3.3) Stunting Normal Stunted (HAZ < -2) 58(50.9) 56(49.1) 215(50.7) 209(49.3) 1 2.2 (1.43, 3.44) * Treatment guide line Old New 71(62.8) 42(37.2) 272(64.2) 152(35.8) 1.5(CI=1.20,2.27) * 1 Baseline regimen Non nevirapine Nevirapine 34(29.9) 80(70.1) 153(36.1) 271(63.9) 1 2.72 (1.13–6.54) * *Significant predictors in the multivariate analysis Discussion This study has identified very important information regarding the predicters and time to treatment failure among HIV-positive children on antiretroviral therapy (ART), which can help planners and decision-makers undertake activities to prevent early first-line treatment failure. There were 114 (21.2%) treatment failures among children who began ART from September 11, 2006, to September 10, 2021. Compared to the UNAIDS cut-off reference range of less than 10%, this rate of treatment failure was unacceptably high [ 20 ]. The most common type of failure was virological failure, followed by clinical and immunological failure. These results were greater than those reported for the different regions of Ethiopia, including Addis Ababa (14.1%) [ 21 ], the Amhara Regional State (12.19%) [ 20 ], and Jimma University Hospital (11.5%) [ 22 ]; moreover, the pooled prevalence of treatment failure was 15.3% [ 22 ]. Moreover, ART treatment failure among children reported in other parts of Ethiopia, including University of Gondar Hospital (18.2%), [ 23 ] Black Lion Hospital (22.6%)[ 24 ], and Fiche and Kuyu Hospitals (18.9%)[ 23 ], is consistent with these findings. This may be due to similarities in the study period and design. However, this percentage was lower than that in Ghana (29%), Tanzania (57%), Uganda (29%), and Mozambique (29%), according to previous reports[ 25 ]. This could be explained by the fact that the current study included children under the age of 15 years, but others up to the age of 18 years and the time to diagnosis of treatment failure were different; that is, at least 6 months were included in this study, but less time was included in the other studies. In the present study, the first-line ART failure rate was 4.53 per 1000 person-months. This rate is greater than the 2.2 per 1000 person-months observed in the Amhara Region, Ethiopia [ 26 ]. WHO stage III and IV, poor adherence to ART, stunting, no change in regimen, and poor ART adherence were found to be statistically significant predictors of ART failure. Children in advanced WHO clinical stages (stages III and IV) were three times more likely than their peers in WHO stages I and II to experience treatment failure during the commencement of ART, similar to the findings of other studies conducted in Mozambique and Uganda [ 20 ]. Children in advanced WHO clinical stages are more likely to have extensive immune suppression and a higher rate of comorbidities, which increases the chance of ART failure. Furthermore, children with advanced disease may experience drug side effects, particularly in the first six months, complicating disease progression even further [ 27 ]. Children with poor adherence to ART regimens had a 6.6 times greater risk of first-line ART failure than did their peers (AHR = 6.6, 95% CI = 4.11–10.66). Previous studies conducted in Ethiopia [ 28 ], Rwanda [ 29 ], Uganda [ 30 ] and Tanzania [ 31 ] reported similar results. This is because a high degree of sustained adherence is required to suppress viral replication and improve immunological and clinical results, lowering the likelihood of ARV treatment resistance and reducing the danger of HIV transmission. In contrast, poor adherence to antiretroviral therapy (ART) is common in the treatment of HIV-positive children and adolescents due to a variety of factors, including regimens for children, which often require the use of multiple pills with frequent dosing requirements, each with the potential for adverse effects and drug interactions, a limited selection of paediatric formulations, and poor palatability of liquid formulations. Adherence may also be influenced by a child's age and developmental stage, as this age group needs assistance from others to take medication on time and may have difficulty swallowing tablets [ 19 ]. Another possibility is that poor drug adherence leads to HIV-related viral resistance and, as a result, treatment failure. Furthermore, because children rely on their caregivers for their care, if the child's progress is poor, caregivers may experience hopelessness, carelessness, and loss as a result of the treatment cascade. With respect to nutritional status, children with stunted nutritional status were 2.2 times more likely to develop ART treatment failure than were those with normal nutritional status. The findings of studies undertaken in Ethiopia and other African countries were consistent with the current findings[ 32 – 34 ]. This could be because stunted children may have had poorer baseline health and ART compliance than normal children. In reality, HIV affects nutritional status on its own, increasing susceptibility to the virus and hastening disease progression in malnourished children [ 21 , 35 ]. Furthermore, stunted children may have had a simultaneous opportunistic infection that caused them to miss out on receiving their medications [ 36 ]. In addition, children whose regimens were not changed were 4.4 times more likely to experience ART treatment failure than were those whose regimens were changed. It is possible that the majority of previous regimens include adverse effects that lead to advanced disease and complications, which can ultimately lead to death. For example, AZT regimens can lead to anaemia, which exacerbates the progression of the disease [ 23 ]. This was further confirmed by the fact that the failure rate prior to 2019 was greater than the rate from 2019 onwards, and children who received NVP-based NNRT had a 2.72-fold greater chance of treatment failure than did those who did not receive nevirapine. This finding was supported by studies conducted in South Africa, [ 37 ], Uganda and Tanzania [ 31 , 38 ]. This could be because nevirapine produces adverse symptoms such as rash, nausea, fatigue, fever, headache, vomiting, diarrhea, and abdominal discomfort, which can make it difficult to adhere to a treatment regimen and lead to treatment failure [ 25 ]. Finally, those children who were still treated based on the old guidelines were 1.5 times more likely to experience ART failure than were those who were treated based on the new guidelines. This result was supported by the comprehensive National ART Guidelines 2018. According to the guidelines, due to side effects and treatment failure, nevirapine-based regimens should be changed to DTG regimens containing drugs when the patient ages from 6 weeks to 10 years and the weight > = 20 kg[ 20 ]. However, among those children who developed treatment failure, only 37.2% changed their guidelines to new ones. These findings are consistent with the results of the change in regimen and nevirapine-based regimen use. Moreover, for those children with treatment failure, 71.1% were older than or equal to five years, and 73.3% had a viral load < 1000 copies/ml. These criteria can be used to guide the new guidelines even though they are not practical. This may be due to inappropriate training given for health professionals or drug shortages. Conclusion Compared to the UNAIDS cut-off value of 10%, the prevalence of ART treatment failure (21.2%) in this study area was unacceptably high [ 39 ]. Despite efforts to improve access to ART, the issue of a higher treatment failure rate has recently become a hot topic. Advanced WHO stages, poor adherence to ART, stunting, use of a nevirapine-based regimen, treatment in the old guidelines and no change in regimen were associated with a greater risk of treatment failure. Therefore, continuous and extensive follow-up, strict adherence to the new treatment guidelines, training of ART clinic staff, prospective study design, and investigation of the reasons why the majority of children were put on the old guidelines were recommended. Abbreviations AHR Adjusted Hazard Ratio AIDS Acquired Immune Deficiency Syndrome ART Antiretroviral Therapy CPT Cotrimoxazole prophylaxis CD4 Cluster of Differentiation 4 cells CHR Crude hazard ratio HIV Human immunodeficiency viruses HAART Highly active antiretroviral therapy HAZ Height for Age Z score UNICEF United Nations International Children’s Emergency Fund UNAIDS Joint United Nations Program on HIV/AIDS WAZ Weight for Age Z score WHO World Health Organization Declarations Ethics approval and consent to participate The protocol was approved by the Research Ethics Committee of the School of Nursing, College of Health Sciences, Addis Ababa University. Waiver of informed consent from individual patients was obtained from the Research Ethics Committee as the study was a retrospective review of medical records. Patient data were collected and analysed unanimously. Consent for publication: Not applicable Availability of data and materials The datasets used and/or analysed 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:we did not receive funding for this work. Authors' contributions AK and ET: Substantially contributed to the conception, design, acquisition, analysis, and interpretation of the data and to the drafting and revision of the manuscript. MA: advised on the study design and data collection and revised the manuscript. All the authors approved the submitted version and agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work Acknowledgements We would like to express our heartfelt gratitude and appreciation to the study participants, health institutions, health care workers involved in this study and Addis Ababa University. References UNAIDS. Global HIV statistics, FACT SHEET 2022. Acccedd on Nov; 2022. Ethiopian Public Health Institute. : HIV Related Estimates and Projections in Ethiopiafor the Year 2021–2022. In. Addis Ababa; 2022. Penazzato M, Townsend CL, Rakhmanina N, Cheng Y, Archary M, Cressey TR, Kim MH, Musiime V, Turkova A, Ruel TD, et al. Prioritizing the most needed paediatric antiretroviral formulations: the PADO4 list. Lancet HIV. 2019;6(9):e623–31. Kharsany AB, Karim QA. HIV Infection and AIDS in Sub-Saharan Africa: Current Status, Challenges and Opportunities. Open AIDS J. 2016;10:34–48. Blanco J, Clotet B. Learning from drug changes in antiretroviral therapy. AIDS. 2013;27(5):833–4. Goga A, Bekker LG, Van de Perre P, El-Sadr W, Ahmed K, Malahleha M, Ramraj T, Ramokolo V, Magasana V, Gray G. Centring adolescent girls and young women in the HIV and COVID-19 responses. Lancet. 2020;396(10266):1864–6. Ebissa G, Deyessa N, Biadgilign S. Predictors of early mortality in a cohort of HIV-infected children receiving high active antiretroviral treatment in public hospitals in Ethiopia. AIDS Care. 2015;27(6):723–30. Bernheimer JM, Patten G, Makeleni T, Mantangana N, Dumile N, Goemaere E, Cox V. Paediatric HIV treatment failure: a silent epidemic. J Int AIDS Soc. 2015;18(1):20090. Gelaw B, Mulatu G, Tesfa G, Marew C, Chekole B, Alebel A. Magnitude and associated factors of virological failure among children on ART in Bahir Dar Town public health facilities, Northwest Ethiopia: a facility based cross-sectional study. Ital J Pediatr. 2021;47(1):84. Getaneh T, Negesse A, Dessie G, Desta M, Assemie MA, Tigabu A, Gelaye K, Alemu AA, Lebu S. Treatment failure and its associated factors among children receiving highly active antiretroviral therapy in Ethiopia: A systematic review and meta-analysis. SAGE Open Med. 2022;10:20503121221081335. Haile GS, Berha AB. Predictors of treatment failure, time to switch and reasons for switching to second line antiretroviral therapy in HIV infected children receiving first line anti-retroviral therapy at a Tertiary Care Hospital in Ethiopia. BMC Pediatr. 2019;19(1):37. Sibhat M, Kassa M, Gebrehiwot H. Incidence and Predictors of Treatment Failure Among Children Receiving First-Line Antiretroviral Treatment in General Hospitals of Two Zones, Tigray, Ethiopia, 2019. Pediatr Health Med Ther. 2020;11:85–94. Koye DN, Ayele TA, Zeleke BM. Predictors of mortality among children on Antiretroviral Therapy at a referral hospital, Northwest Ethiopia: a retrospective follow up study. BMC Pediatr. 2012;12:161. World Health Organization. : World health statistics 2016: monitoring health for the SDGs, sustainable development goals. In. Geneva: World Health Organization; 2016. Yassin S, Gebretekle GB. Magnitude and predictors of antiretroviral treatment failure among HIV-infected children in Fiche and Kuyu hospitals, Oromia region, Ethiopia: a retrospective cohort study. Pharmacol Res Perspect. 2017;5(1):e00296. Emmett SD, Cunningham CK, Mmbaga BT, Kinabo GD, Schimana W, Swai ME, Bartlett JA, Crump JA, Reddy EA. Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: a cross-sectional study. J Acquir Immune Defic Syndr. 2010;54(4):368–75. Shumetie A, Moges NA, Teshome M, Gedif G. Determinants of Virological Failure Among HIV-Infected Children on First-Line Antiretroviral Therapy in West Gojjam Zone, Amhara Region, Ethiopia. HIV AIDS (Auckl). 2021;13:1035–44. Azmeraw M, Workineh Y, Girma F, Kassaw A, Kerebeh G, Tsedalu A, Tigabu A, Mengesha T, Dagnaw E, Temesgen D, et al. Incidence and predictors of initial antiretroviral therapy regimen change among children in public health facilities of Bahir Dar City, Northwest Ethiopia, 2021: multicenter retrospective follow-up study. BMC Pediatr. 2022;22(1):186. Sibhat M, Kassa M, Gebrehiwot H. Incidence and predictors of treatment failure among children receiving first-line antiretroviral treatment in general hospitals of two zones, Tigray, Ethiopia, 2019. Pediatr Health Med Ther. 2020;11:85. Iroha E, Esezobor CI, Ezeaka C, Temiye EO, Akinsulie A. Adherence to antiretroviral therapy among HIV-infected children attending a donor-funded clinic at a tertiary hospital in Nigeria. Afr J AIDS Res. 2010;9(1):25–30. Rojo P, Carpenter D, Venter F, Turkova A, Penazzato M. The HIV drug optimization agenda: promoting standards for earlier investigation and approvals of antiretroviral drugs for use in adolescents living with HIV. J Int AIDS Soc. 2020;23:e25576. Endalamaw A, Mekonnen M, Geremew D, Yehualashet FA, Tesera H. Habtewold TDJBph: HIV/AIDS treatment failure and associated factors in Ethiopia: meta-analysis. 2020, 20(1):1–12. Shumetie A, Moges NA, Teshome M, Gedif G. Determinants of Virological Failure Among HIV-Infected Children on First-Line Antiretroviral Therapy in West Gojjam Zone, Amhara Region, Ethiopia. HIV/AIDS (Auckland NZ). 2021;13:1035. Dow DE, Shayo AM, Cunningham CK, Reddy EAJB. Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up. 2014, 14(1):1–9. Brooks AD, Sanoski C, Hajjar ER, Overholser BR. Naplex 2017 Strategies, Practice & Review with 2 Practice Tests: Online + Book. Simon and Schuster; 2017. Zenebe E, Washo A, Addis Gesese A. Time to First-Line Antiretroviral Treatment Failure and Its Predictors among HIV-Positive Children in Shashemene Town Health Facilities, Oromia Region, Ethiopia, 2019. ScientificWorldJournal 2021, 2021:8868479. Costenaro P, Penazzato M, Lundin R, Rossi G, Massavon W, Patel D, Nabachwa S, Franceschetto G, Morelli E, Bilardi D. Predictors of treatment failure in HIV-positive children receiving combination antiretroviral therapy: cohort data from Mozambique and Uganda. J Pediatr Infect Dis Soc. 2015;4(1):39–48. Yassin S, Gebretekle GB. Magnitude and predictors of antiretroviral treatment failure among HIV-infected children in Fiche and Kuyu hospitals, Oromia region, Ethiopia: a retrospective cohort study. Pharmacol Res Perspect. 2017;5(1):e00296. Mutwa PR, Boer KR, Asiimwe-Kateera B, Tuyishimire D, Muganga N, Lange JM, van de Wijgert J, Asiimwe A, Reiss P, Geelen SP. Safety and effectiveness of combination antiretroviral therapy during the first year of treatment in HIV-1 infected Rwandan children: a prospective study. PLoS ONE. 2014;9(11):e111948. Sebunya R, Musiime V, Kitaka SB, Ndeezi G. Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. AIDS Res therapy. 2013;10(1):1–10. Emmett SD, Cunningham CK, Mmbaga BT, Kinabo GD, Schimana W, Swai ME, Bartlett JA, Crump JA, Reddy EA. Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: a cross-sectional study. J Acquir Immune Defic Syndr. 2010;54(4):368. Kumar P. Adult pulmonary tuberculosis as a pathological manifestation of hyperactive antimycobacterial immune response. Clin Translational Med. 2016;5(1):1–7. Zoufaly A, Fillekes Q, Hammerl R, Nassimi N, Jochum J, Drexler JF, Awasom CN, Sunjoh F, Burchard GD, Burger DMJAT. Prevalence and determinants of virological failure in HIV-infected children on antiretroviral therapy in rural Cameroon: a cross-sectional study. 2013, 18(5):681–90. Makadzange A, Higgins-Biddle M, Chimukangara B, Birri R, Gordon M, Mahlanza T, McHugh G, Van Dijk J, Bwakura-Dangarembizi M. Ndung’u TJPO: Clinical, virologic, immunologic outcomes and emerging HIV drug resistance patterns in children and adolescents in public ART care in Zimbabwe. 2015, 10(12):e0144057. Federal H, Prevention A. Control Office Federal Ministry of Health. Guidelines for prevention of mother-to-child transmission of HIV in Ethiopia 2007. Negese D, Addis K, Awoke A, Birhanu Z, Muluye D, Yifru S, Megabiaw B. HIV-positive status disclosure and associated factors among children in North Gondar, Northwest Ethiopia. International Scholarly Research Notices 2012, 2012. Davies M-A, Moultrie H, Eley B, Rabie H, Van Cutsem G, Giddy J, Wood R, Technau K, Keiser O, Egger M. Virologic failure and second-line antiretroviral therapy in children in South Africa-The IeDEA Southern Africa Collaboration. Journal of acquired immune deficiency syndromes ( 1999 ) 2011, 56(3):270. Kamya MR, Mayanja-Kizza H, Kambugu A, Bakeera-Kitaka S, Semitala F, Mwebaze-Songa P, Castelnuovo B, Schaefer P, Spacek LA, Gasasira AF. Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. JAIDS J Acquir Immune Defic Syndr. 2007;46(2):187–93. Organization WH. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. World Health Organization; 2016. Additional Declarations No competing interests reported. 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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-3887288","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":268950383,"identity":"c3d37e69-adcb-44ba-a09d-d871426b1fa5","order_by":0,"name":"Abere Kassie","email":"","orcid":"","institution":"Debre Markos University","correspondingAuthor":false,"prefix":"","firstName":"Abere","middleName":"","lastName":"Kassie","suffix":""},{"id":268950384,"identity":"476f3beb-2e8a-4398-80cf-dab1bc1c3080","order_by":1,"name":"Makonnen Adimasu","email":"","orcid":"","institution":"Addis Ababa University","correspondingAuthor":false,"prefix":"","firstName":"Makonnen","middleName":"","lastName":"Adimasu","suffix":""},{"id":268950385,"identity":"4529a63e-62d1-44b4-85c1-bdef69b6295b","order_by":2,"name":"Erdaw Tachbele","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYHACAyC2YWCQIE1LQhrpWg6ToIVf+vDGz7w/zif2z24++IChxiaaoBbJvrRiaZ6E24kz7hxLNmA4lpbbQNBVZ3gMpHOAWhpu5JhJMDYcJqzF/gyP8e+chHOJ84nWYsDDYwa05UDiBqK1SJxhK7P+k5ZsvPFGWrJBAjF+4e9h3nxzho2d7LwbyQcffKixIawFBhzBKhOIVQ4C9qQoHgWjYBSMghEGAApVPt0JN4pHAAAAAElFTkSuQmCC","orcid":"","institution":"Addis Ababa University","correspondingAuthor":true,"prefix":"","firstName":"Erdaw","middleName":"","lastName":"Tachbele","suffix":""}],"badges":[],"createdAt":"2024-01-22 07:59:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3887288/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3887288/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50317580,"identity":"d589e1ce-b46e-4cd8-b7fc-8a049cb351ad","added_by":"auto","created_at":"2024-01-29 16:26:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":55499,"visible":true,"origin":"","legend":"\u003cp\u003eThe overall Kaplan‒Meier survival estimate for time to treatment failure based on duration of ART (with 95% CI) in East Gojjam Zone public health facilities, North West Ethiopia 2022.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3887288/v1/3780b3e9c3f8d12661563539.png"},{"id":65695805,"identity":"9a9c7454-3d29-49d3-9728-7912df91db2c","added_by":"auto","created_at":"2024-10-01 11:16:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":997214,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3887288/v1/38783711-b8f3-4321-95e5-84eecb418087.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Incidence and Predictors of Treatment Failure Among Children Receiving First-Line Antiretroviral Therapy in East Gojjam, Ethiopia: A Fifteen-year Retrospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAt the end of 2021, 38.4\u0026nbsp;million people were living with HIV worldwide. A total of 1.7\u0026nbsp;million were children, and 110,000 of them died due to HIV-related illnesses in the same year [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In Ethiopia, a total of 612,925 HIV patients were living, 41,788 of whom were children at the end of 2021[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough ART significantly improves the quality of life of PLWH, treatment failure is associated with a high risk of mortality following the start of ART. ART failure in children is classified as virologic, immunologic, clinical failure, or a combination of the three[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHIV-infected children are more vulnerable to negative outcomes, including death, if there is no life-saving ART and regular medical supervision [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Even if pediatric ART coverage increases, more children than adults develop treatment failure because they rely on their parents or caregivers to obtain healthcare services[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePediatric ART failure rates range from 19.3% to more than 32.0% in resource-limited settings[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Studies conducted in several African countries have reported that the prevalence of pediatric ART failure ranges from 15\u0026ndash;57%[\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In a recent meta-analysis, the pooled prevalence of treatment failure among children in Ethiopia was 12.34% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies conducted in different African countries, including Ethiopia, have indicated that poor ART adherence, advanced WHO clinical staging, and opportunistic infections are significant predictors of childhood treatment failure[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Childhood ART failure was also found to be associated with the baseline regimen and changes in the regimen. According to studies conducted in Ethiopia and Tanzania, children who received nevirapine (NVP)-based treatment regimens were two times more likely than those who received efavirenz and protease inhibitor-based treatment regimens to experience treatment failure[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThere is limited information on the rate and determinants of ART failure among children in the current study area, particularly after the initiation of the new ART guide line in 2019 in Ethiopia. Hence, this study was designed to determine the incidence rate and predictors of ART failure among children in public health facilities in East Gojjam, Ethiopia.2021\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design, period and setting\u003c/h2\u003e \u003cp\u003eA multicenter facility-based retrospective follow-up study was conducted from September 11,2006 to September 10, 2021 to assess the incidence of treatment failure and its predictors at public health facilities in the East Gojjam Zone. The zone is located 300 kilometers from Addis Ababa, the capital of Ethiopia, and has a total population of 2,719,118 and 632,353 households. The Zone has 423 health posts, 102 health centers, 9 primary hospitals, one general hospital, and one referral hospital. Of these, only 34 health institutes provided ART services for a total of 903 HIV-positive children in 2021; 11 health facilities (5 hospitals and 6 health centers) were randomly selected as study sites. Specifically, Debre-Markos Referral Hospital, Shegaw Motta General Hospital, Lumame Primary Hospital, Bichena Primary Hospital, Mertule Mariam Primary Hospital, Debre Markos Health Center, Dejen Health Center, Mertule Mariam Health Center, Lumame Health Center, Bichena Health Center, and Amber Health Center were included as study sites.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eAll HIV-positive children under the age of 15 who started ART at East Gojjam Zone Public Health Institutions composed the study population. Children who started ART between September 2006 and September 2021 and who had taken ART for at least six months were included in the study. Children with incomplete admission information, such as age, type of caregiver, address, sex, CD4 count, hemoglobin level, ART beginning time, and who were on ART for less than six months, were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSample size determination and sampling procedure\u003c/h2\u003e \u003cp\u003eThe sample size was calculated using the Epi Info version 7 software's double population proportion difference formula, taking into account severe underweight, severe wasting, hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;10 g/dl, CD4 count or % below the threshold and WHO clinical stage III/IV from previously conducted studies[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The final and maximum sample size, 558 individual charts, was provided by the sample size that we calculated based on the CD4 count or percentage below the threshold, considering the following assumptions: a percentage of exposed (26%) and nonexposed (16%), a ratio of one to one exposed to nonexposed (1:1), a 95% confidence level, a 1.63 hazard ratio, and 80% power. Medical records were arranged for all 903 children under 15 years of age who began ART between September 11, 2006, and September 10, 2021, at the 11 selected health facilities. Following a proportionate allocation of the 558 study participants to each study site, data were extracted using a basic random sample approach from the records of each enrolled child over a period of 15 years.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eVariables\u003c/h2\u003e \u003cp\u003eThe incidence rate of ART failure and time to ART failure were the dependent variables. The independent variables were sociodemographic, laboratory and clinical characteristics. In addition, sociodemographic variables of parents/caregivers, including residence, marital status, occupation, age, sex and HIV serostatus, were included. Furthermore, WHO clinical stage, CD4 count, hemoglobin level, functional status (for \u0026ge;\u0026thinsp;5 years), developmental status (for \u0026lt;\u0026thinsp;5 years), opportunistic infection, prophylaxis therapy (CPT and INH), duration of ART treatment, type of ART regimen, pharmacological adverse effects, adherence to ART, and nutritional status (wasting, stunting, underweight and BMI for age) were considered predictor variables.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eData collection tool\u003c/h2\u003e \u003cp\u003eThe standardized ART entry and follow-up formats of the Ministry of Health were utilized to develop the data extraction tools. The data were collected from children's charts and electronic databases by data collectors using the developed data extraction sheet.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData quality control\u003c/h2\u003e \u003cp\u003eThe information was gathered by eleven nurses who had been trained in comprehensive HIV care and were involved in patient follow-up. A pretest was conducted on 10% of the sample at Debre Work Primary Hospital. Both the data collectors and supervisors received a one-day training session on the data collection tool and procedures. The data quality was also ensured by using the right data gathering instrument and maintaining constant oversight. Checklists were assigned codes. Every day, the data collectors and supervisors examined all the obtained data for completeness.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eData processing and analysis\u003c/h2\u003e \u003cp\u003eThe collected data were checked for completeness and consistency and then coded and recorded in SPSS version 25. The data were subsequently cleaned and analysed using STATA version 14. Descriptive statistics were computed to determine frequencies and summary statistics (mean, standard deviation and percentage). WHO AnthroPlus version 1.04 software was used to generate Z scores (WAZ, HAZ and WHZ/BIAZ) to determine nutritional status. The Kaplan\u0026ndash;Meier survival curve was used to estimate the time to develop treatment failure after the initiation of antiretroviral therapy. Log rank tests were applied to compare survival curves of categorical predictor variables. To determine the effect of the predictors on the duration of ART failure, a bivariable Cox regression proportional hazard model was fitted for each explanatory variable. Finally, those variables with p values\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;0.25 in the bivariant analysis were fitted to the multivariable Cox proportional hazard regression model. The hazard ratio (HR) with a 95% confidence interval (CI) and p value were used to predict the strength of the association and identify statistically significant results. A P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate a statistically significant association. The Cox proportional hazard model assumption was confirmed using the scaled Schoenfeld residual test (a P value greater than 0.05 met the assumption) and graphically with the log-log Cox adjusted survival estimate. The fitness of the model was checked using the Cox\u0026ndash;Snell residual test.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eOperational definitions\u003c/h2\u003e \u003cp\u003e \u003cb\u003eIn this study, \u0026ldquo;event\u0026rdquo;\u003c/b\u003e was considered the time to treatment failure, treatment failure, and its predicters. \u003cb\u003eCensoring was\u003c/b\u003e other than the event (transfer outs, defaulters, deaths, patients who did not develop treatment failure during the study period, or switchers due to factors other than first-line ART failure). The time to occurrence of an event or censored cases was measured in months. \u003cb\u003eDisclosure\u003c/b\u003e: is defined as when the child knows his/her HIV and treatment status irrespective of the source. \u003cb\u003eDuration of ART\u003c/b\u003e: the time between the start date of ART and the last contact date with the health facility during data collection. \u003cb\u003eUndernutrition\u003c/b\u003e: If the child has one height/age\u0026lt;-2, weight/age\u0026lt;-2, weight/height \u0026lt;-2 or BMI for age \u0026lt;-2 standard deviations according to the WHO curve. \u003cb\u003eThe functional status\u003c/b\u003e was defined as working (playing, doing normal activities, and going to school), ambulatory (able to perform daily living activities), or bedridden (not able to perform daily living activities) (23). \u003cb\u003eAdherence\u003c/b\u003e: taking the right ARV medication at the right dose at the right time every day and exactly as long as they were prescribed for life. were classified as follows: good if adherence was \u0026ge;\u0026thinsp;95% (1 dose of 30 doses or 2 doses of 60 dose missed), fair if adherence was between 85 and 94% (2 and 4 doses of 30 dose or 4 and 9 doses of 60 dose were missed), and poor if adherence was \u0026lt;\u0026thinsp;85% (\u0026ge;\u0026thinsp;5 dose of 30 dose or \u0026ge;\u0026thinsp;10 dose of 60 dose was missed) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. \u003cb\u003eDevelopmental status was\u003c/b\u003e defined as appropriate (if a child has reached a milestone for age), delay (if the child fails to reach a milestone for age) or regression (loss of appropriate developmental milestones due to illness) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eSociodemographic characteristics of children on ART\u003c/h2\u003e\n \u003cp\u003eA total of 538 (96.4%) records of children with HIV were included in the final analysis. Of these, 285 (53.0%) were males, the mean age was 7.25 (95% CI\u0026thinsp;=\u0026thinsp;6.95\u0026ndash;7.58) years, and 398 (74%) of the children were older than five years. The majority 389 ( 72.3%) were urban residents, 378 (70.3%) were living with their parents, and almost half were living with their parents; 274 (50.9%) were alive mothers and fathers (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSociodemographic characteristics of children on ART at East Gojjam Zone public health facilities, North West Ethiopia, 2006\u0026ndash;2021 (n\u0026thinsp;=\u0026thinsp;538)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCategory\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFrequency\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercent\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\n \u003cp\u003eSex of children\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.0\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=\"char\"\u003e\n \u003cp\u003e253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eAge of children\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt; years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;1 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003eRelation of child to care giver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUncle/aunt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSister/brother\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrand parent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGuardian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eReligion of parent/care giver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuslim\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOrthodox\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e452\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e85.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eResidence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e389\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eMarital status of caregiver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMarried\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSingle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWidowed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDivorced\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003eHIV status of parent/caregiver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBoth positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMother positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFather positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFather negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003eParent status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBoth alive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOnly mother alive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOnly father alive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBoth died\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUn known\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.4\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=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eClinical, laboratory, and ART baseline characteristics\u003c/h2\u003e\n \u003cp\u003eAt the time of ART initiation, 318 children (59.1%) had opportunistic infections. The mean and median haemoglobin levels were 12.059 mg/dl and 12.2 mg/dl (95% CI\u0026thinsp;=\u0026thinsp;11.901, 12.217), respectively. In terms of WHO clinical stage, 281 (52.2%) patients were in stage I or stage II, and 73.7% of the children who were enrolled in ART had a viral load lower than 1000 copies/ml at baseline. With respect to developmental status, 383 (71.1%) were appropriate for their age. At the time of ART initiation, 391 (72.7%) children\u0026rsquo;s CD4 count was below the threshold. A total of 197 (36.6%) of the study participants were eligible for ART treatment due to a low CD4 count (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline clinical and immunological characteristics of children on first-line ART in East Gojjam Zone Public Health Facilities, Ethiopia, 2006\u0026ndash;2021 (n\u0026thinsp;=\u0026thinsp;538)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCategory\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFrequency\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercent\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\n \u003cp\u003eOpportunistic infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"6\"\u003e\n \u003cp\u003eTypes of opportunistic infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiarrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCandidiasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSkin Rash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHerpes Zoster\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eFunctional status\u0026thinsp;\u0026ge;\u0026thinsp;5 years (N\u0026thinsp;=\u0026thinsp;398)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWorking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmbulatory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBed ridden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eDevelopmental status\u0026thinsp;\u0026lt;\u0026thinsp;5 years (N\u0026thinsp;=\u0026thinsp;140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAppropriate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDelayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRegressed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eWHO staging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStage I/II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e281\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStage III/IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eHemoglobin level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;10 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;10 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCD4 count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbove thresh hold\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBelow thresh hold\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eViral load\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;1000 copies/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e315\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.6\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 copies/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003eART eligibility criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWHO staging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCD4 count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBoth clinical and CD4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e190\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTest and treat all\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.1\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=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eFollow-up data on factors related to ART and other medications among the study participants\u003c/h2\u003e\n \u003cp\u003eThe most common baseline regimen was 4c (AZT-3TC-NVP), which was utilized by 45.5% of the patients, followed by 4a (d4t-3TC-NVP), which was used by 22.5%, and the majority of the patients (393 [73.0%]) were on a nevirapine-based regimen. The great majority of children (92.6%) received prophylaxis, 93% of whom were on CPT. During the study period, only 108 (20.1%) patients changed their regimen, mainly because of drug stocking out 31 (28.7%), and 364 (64.3%) patients were found to have poor treatment adherence. Regarding the nutritional status of the study participants, 86 (16.0%) had stunted growth. Among those under five years of age, 94 (17.5%), 125 (23.2%), and 86 (16.0%) were wasting, underweight, and stunted, respectively (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\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\u003eFollow-up data on factors related to ART and other medications among children on first-line ART in East Gojjam Zone Public Health Facilities, Ethiopia, 2006\u0026ndash;2021 (n\u0026thinsp;=\u0026thinsp;538)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCategory\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFrequency\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercent\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=\"8\"\u003e\n \u003cp\u003eBaseline regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4a(d4t-3TC-NVP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4b (d4t-3TC-EFV)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4c (AZT-3TC-NVP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4d (AZT-3TC-EFV)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1e (TDF-3TC-EFV)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (ABC-3TC-NVP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1g(ABC-3TC-EFV)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther (1c,4i,4j,4g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eRegimen type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNevirapine based regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e393\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone nevirapine based regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eTaking prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e498\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e92.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eType of prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e478\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e96.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eINH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBoth CPT and INH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSide effect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e514\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eType of side effect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eToxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSkin Rash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eRegimen change\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=\"char\"\u003e\n \u003cp\u003e430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003eReason for drug change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrug side effect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOpportunistic infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTreatment failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrug stock out\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrug optimization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eAdherence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFair\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003eSurvey end point\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e348\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLost to follow -up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTransferred out\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrop out\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eFirst line Treatment Failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eTypes of Treatment Failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVirological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImmunological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinical\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eWeight for height/length (\u0026lt;\u0026thinsp;5 year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWasted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eWeigh for age (\u0026lt;\u0026thinsp;5 year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnder weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eHeight for age (\u0026lt;\u0026thinsp;5 year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e452\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e84.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStunted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eWeight for age (age\u0026thinsp;\u0026lt;\u0026thinsp;10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e409\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76 .0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnder weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24. 0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eBody mass index for age (\u0026ge;\u0026thinsp;5 year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e452\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e84.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThinness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 .0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eHeight/length for age (\u0026lt;\u0026thinsp;15 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e445\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStunted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.2\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\u003eIncidence and survival status of treatment failure\u003c/h2\u003e\n \u003cp\u003eIn this study, 538 participants were followed for a total of 15 years, with a minimum of 6 months and a maximum of 180 months, resulting in 81,295 child-months of observation risk, with a mean and median follow-up of 43.6 and 37 months, respectively. Of the 538 participants, 114 (21.2%) had treatment failures (cases), and 424 (78.8%) were censored. Of those who were censored, 342 (63.6%) participants were alive, 137 (25.5%) were transferred out, 34 (6.3%) died, 20 (3.7%) dropped out, and 5 (0.9%) were lost to follow-up. Among the treatment failures, 85 (74.6%) were virological, 19 (16.7%) were immunological, and 10 (8.8%) were clinical failures (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The cumulative incidence of treatment failure was 21% (95% CI: 17.7\u0026ndash;24.7), and the overall treatment failure incidence density rate (IDR) in the study was 4.53 per 1000 person-months. The cumulative probabilities of failure at the end of the 7th, 24th, and 4th months were 7% and 4.4%, respectively. This study showed that the highest incidence of TF occurred between 108\u0026ndash;109, 10\u0026ndash;11, and 24\u0026ndash;25 months after starting ART. As the length of survival increased, the hazard of time to TF increased (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eBivariate and multivariate Cox proportional hazard analyses\u003c/h2\u003e\n \u003cp\u003eAccording to our bivariate analysis, children who were WHO clinical stage III/IV had shorter survival than did those with WHO clinical stage I/II. The mean survival time was 52.4 months (95% CI\u0026thinsp;=\u0026thinsp;41.70, 63.08) for WHO stage I/II and 38.7 months (95% CI\u0026thinsp;=\u0026thinsp;30.66, 48.82) for WHO stage III/IV (P value\u0026thinsp;=\u0026thinsp;0.04). Children with stunted nutritional status had shorter survival times than did those with normal nutritional status, with mean and median survival times of 36.3 months (95% CI\u0026thinsp;=\u0026thinsp;29.292, 43.216) and 31.0 months (95% CI\u0026thinsp;=\u0026thinsp;19.603, 42.397), respectively, versus 51.7 months (95% CI\u0026thinsp;=\u0026thinsp;41.004, 62.340) and 44.0 months (95% CI\u0026thinsp;=\u0026thinsp;35.609, 52.391) (p value\u0026thinsp;=\u0026thinsp;0.012). Participants with poor adherence to ART had shorter survival times than did those with fair and good adherence to ART, and children with fair adherence to ART had shorter survival times than did those with good adherence, with mean survival times of 26.2 months (CI\u0026thinsp;=\u0026thinsp;18.974, 33.407) and 46.2 months (CI\u0026thinsp;=\u0026thinsp;28.983, 63.462) and a median survival time of 48.6 months (CI\u0026thinsp;=\u0026thinsp;40.063, 57.205) respectively (p. value\u0026thinsp;=\u0026thinsp;0.003). In the present study, children whose regimen was not changed had shorter survival times than did those whose regimen was changed, with mean survival times of 36.5 (CI\u0026thinsp;=\u0026thinsp;29.904, 43.106) and 50.7 (CI\u0026thinsp;=\u0026thinsp;40.112, 61.265) months, respectively (p value\u0026thinsp;=\u0026thinsp;0.019). In the present study, prolonging the initial regimen was more hazardous for treatment failure than counterpart. The mean duration of treatment with the initial regimen was 42.1 months. Children who received the nevirapine-based regimen had a shorter survival time (mean 39.2 months) at treatment failure than did those who did not (mean 44.2 months) (P value\u0026thinsp;=\u0026thinsp;0.043).\u003c/p\u003e\n \u003cp\u003eBased on the new WHO 2019 recommendations for antiretroviral treatment, global community identified a new formulation of the fixed-dose combination (FDC) of tenofovir (TDF) 300 mg\u0026thinsp;+\u0026thinsp;lamivudine (3TC) 300 mg\u0026thinsp;+\u0026thinsp;dolutegravir (DTG) 50 mg (TLD) for all eligible adults, adolescents and children aged\u0026thinsp;\u0026gt;\u0026thinsp;10 years and weighing 35 kg or more (WHO, 2018). Accordingly, the incidences of treatment failure among the study participants before and after the new WHO guidelines were 73 (64%) and 41 (36%), respectively. The hazard of treatment failure in the old regimen was 1.5 times greater than that in the new regimen (CI\u0026thinsp;=\u0026thinsp;1.021, 2.273) (p\u0026thinsp;=\u0026thinsp;0.039).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003ePredicators of ART treatment failure\u003c/h2\u003e\n \u003cp\u003eA Cox proportional hazard regression model was used to examine any associations between baseline factors and the probability of ART failure in children on ART. The child\u0026apos;s sex, baseline viral load, OI before and during the follow-up period, disclosure status, baseline regimen, duration of ART, use of prophylaxis, CD4 count, WHO clinical stage, adherence level, height for age, baseline regimen, and implemented treatment guidelines were all eligible for multivariate Cox regression analysis in the bivariate analysis. However, only WHO stage, ART adherence, height for age, regimen change, baseline regimen, and guideline utilized were found to be significant predictors of ART failure in the multivariate analysis (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe incidence of ART failure was 3 times greater in children with WHO stage III or IV disease than in children with WHO stage I or II disease (AHR\u0026thinsp;=\u0026thinsp;3.0 CI\u0026thinsp;=\u0026thinsp;1.3, 7.1). Regarding treatment adherence, children with poor adherence to ART treatment had a 6.6 times greater risk of treatment failure than did their counterparts (AHR\u0026thinsp;=\u0026thinsp;6.6, CI\u0026thinsp;=\u0026thinsp;4.11, 10.66). Furthermore, compared to children who had good adherence to ART, those who had fair adherence were 2.2 times more likely to have treatment failure. In addition, the risk of ART failure was 2.2 times greater in stunted children (HFA-2 Z score) than in their peers (AHR\u0026thinsp;=\u0026thinsp;2.2, CI\u0026thinsp;=\u0026thinsp;1.43, 3.44). Regarding regimen changes, children whose regimen was not changed were 4.4 times more hazardous for ART failure than for those whose regimen was changed (AHR 4.4, CI\u0026thinsp;=\u0026thinsp;1.7, 11.7). Children treated according to the previous treatment guidelines were 1.5 times more likely to experience ART failure than were those treated according to the new treatment guidelines (AHR\u0026thinsp;=\u0026thinsp;1.5, CI\u0026thinsp;=\u0026thinsp;1.20, 2.273). Similarly, children who received the nevirapine-based regimen were 2.72 times more likely to experience ART treatment failure than children who received the non-nevirapine treatment regimen were (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4:\u003c/strong\u003e Cox regression analysis of predictors of ART failure among children on ART in East Gojjam Zone public health facilities, Northwestern Ethiopia, 2022.\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Survival status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAHR (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTF, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCensored, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;1yer\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1-5 year\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026ge;5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3(2.63)\u003c/p\u003e\n \u003cp\u003e30(26.3)\u003c/p\u003e\n \u003cp\u003e81(71.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9(2.1)\u003c/p\u003e\n \u003cp\u003e97(22.9)\u003c/p\u003e\n \u003cp\u003e318(75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1\u003c/p\u003e\n \u003cp\u003e1.2 (0.388, 3.924)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;0.677(0.443,1.034)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResidence\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Urban\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Rural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e83(72.8)\u003c/p\u003e\n \u003cp\u003e31(27.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e306(72.2)\u003c/p\u003e\n \u003cp\u003e118(27.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 1\u003c/p\u003e\n \u003cp\u003e0.679 (0.443, 1.041)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOI during follow up\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Yes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e100(87.7)\u003c/p\u003e\n \u003cp\u003e14(12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e218(51.4)\u003c/p\u003e\n \u003cp\u003e206(48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.5 (1.0, 6.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWHO clinical staging\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Stage I and II\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Stage III and IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24(21.0)\u003c/p\u003e\n \u003cp\u003e90(79.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e168(39.6)\u003c/p\u003e\n \u003cp\u003e256 (60.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3.0 (1.3, 7.1) *\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCD4 count or percent\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Below the threshold\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Above the threshold\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51(44.7)\u003c/p\u003e\n \u003cp\u003e63(53.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e337(79.5)\u003c/p\u003e\n \u003cp\u003e87(20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.4 (1.7, 11.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHemoglobin level\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;10 g/dl\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026ge;10 g/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e87(76.3)\u003c/p\u003e\n \u003cp\u003e27(23.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e182(42.9)\u003c/p\u003e\n \u003cp\u003e242(50.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.1 (1.4, 6.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChange of regimen\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Yes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15(13.2)\u003c/p\u003e\n \u003cp\u003e62(86.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e289(68.2)\u003c/p\u003e\n \u003cp\u003e135(31.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 4.4 (1.7, 11.7) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAdherence\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Good\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Fair\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Poor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e75(65.8)\u003c/p\u003e\n \u003cp\u003e18 (15.8)\u003c/p\u003e\n \u003cp\u003e21(18.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e74(17.5)\u003c/p\u003e\n \u003cp\u003e25(5.9)\u003c/p\u003e\n \u003cp\u003e325(76.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2.2(1.13,4.20)\u003c/p\u003e\n \u003cp\u003e6.6(4.11,10.66) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUnderweight\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Normal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Moderate (WAZ \u0026lt;- 2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Severely (WAZ \u0026lt; -3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e68 (59.6)\u003c/p\u003e\n \u003cp\u003e50(43.9)\u003c/p\u003e\n \u003cp\u003e33(28.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e278(65.6)\u003c/p\u003e\n \u003cp\u003e65(15.3)\u003c/p\u003e\n \u003cp\u003e96(22.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2.0 (0.8, 4.7)\u003c/p\u003e\n \u003cp\u003e1.2 (0.4, 3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStunting\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Normal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Stunted (HAZ \u0026lt; -2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58(50.9)\u003c/p\u003e\n \u003cp\u003e56(49.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e215(50.7)\u003c/p\u003e\n \u003cp\u003e209(49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1\u003c/p\u003e\n \u003cp\u003e2.2 (1.43, 3.44) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTreatment guide line\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Old\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;New\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e71(62.8)\u003c/p\u003e\n \u003cp\u003e42(37.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e272(64.2)\u003c/p\u003e\n \u003cp\u003e152(35.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.5(CI=1.20,2.27) *\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBaseline regimen\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Non nevirapine\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Nevirapine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34(29.9)\u003c/p\u003e\n \u003cp\u003e80(70.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e153(36.1)\u003c/p\u003e\n \u003cp\u003e271(63.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2.72 (1.13\u0026ndash;6.54) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e*Significant predictors in the multivariate analysis\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study has identified very important information regarding the predicters and time to treatment failure among HIV-positive children on antiretroviral therapy (ART), which can help planners and decision-makers undertake activities to prevent early first-line treatment failure.\u003c/p\u003e \u003cp\u003eThere were 114 (21.2%) treatment failures among children who began ART from September 11, 2006, to September 10, 2021. Compared to the UNAIDS cut-off reference range of less than 10%, this rate of treatment failure was unacceptably high [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The most common type of failure was virological failure, followed by clinical and immunological failure. These results were greater than those reported for the different regions of Ethiopia, including Addis Ababa (14.1%) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], the Amhara Regional State (12.19%) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], and Jimma University Hospital (11.5%) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]; moreover, the pooled prevalence of treatment failure was 15.3% [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Moreover, ART treatment failure among children reported in other parts of Ethiopia, including University of Gondar Hospital (18.2%), [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Black Lion Hospital (22.6%)[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], and Fiche and Kuyu Hospitals (18.9%)[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], is consistent with these findings. This may be due to similarities in the study period and design. However, this percentage was lower than that in Ghana (29%), Tanzania (57%), Uganda (29%), and Mozambique (29%), according to previous reports[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This could be explained by the fact that the current study included children under the age of 15 years, but others up to the age of 18 years and the time to diagnosis of treatment failure were different; that is, at least 6 months were included in this study, but less time was included in the other studies.\u003c/p\u003e \u003cp\u003eIn the present study, the first-line ART failure rate was 4.53 per 1000 person-months. This rate is greater than the 2.2 per 1000 person-months observed in the Amhara Region, Ethiopia [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWHO stage III and IV, poor adherence to ART, stunting, no change in regimen, and poor ART adherence were found to be statistically significant predictors of ART failure.\u003c/p\u003e \u003cp\u003eChildren in advanced WHO clinical stages (stages III and IV) were three times more likely than their peers in WHO stages I and II to experience treatment failure during the commencement of ART, similar to the findings of other studies conducted in Mozambique and Uganda [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Children in advanced WHO clinical stages are more likely to have extensive immune suppression and a higher rate of comorbidities, which increases the chance of ART failure. Furthermore, children with advanced disease may experience drug side effects, particularly in the first six months, complicating disease progression even further [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChildren with poor adherence to ART regimens had a 6.6 times greater risk of first-line ART failure than did their peers (AHR\u0026thinsp;=\u0026thinsp;6.6, 95% CI\u0026thinsp;=\u0026thinsp;4.11\u0026ndash;10.66). Previous studies conducted in Ethiopia [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], Rwanda [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], Uganda [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and Tanzania [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] reported similar results. This is because a high degree of sustained adherence is required to suppress viral replication and improve immunological and clinical results, lowering the likelihood of ARV treatment resistance and reducing the danger of HIV transmission. In contrast, poor adherence to antiretroviral therapy (ART) is common in the treatment of HIV-positive children and adolescents due to a variety of factors, including regimens for children, which often require the use of multiple pills with frequent dosing requirements, each with the potential for adverse effects and drug interactions, a limited selection of paediatric formulations, and poor palatability of liquid formulations. Adherence may also be influenced by a child's age and developmental stage, as this age group needs assistance from others to take medication on time and may have difficulty swallowing tablets [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Another possibility is that poor drug adherence leads to HIV-related viral resistance and, as a result, treatment failure. Furthermore, because children rely on their caregivers for their care, if the child's progress is poor, caregivers may experience hopelessness, carelessness, and loss as a result of the treatment cascade.\u003c/p\u003e \u003cp\u003eWith respect to nutritional status, children with stunted nutritional status were 2.2 times more likely to develop ART treatment failure than were those with normal nutritional status. The findings of studies undertaken in Ethiopia and other African countries were consistent with the current findings[\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. This could be because stunted children may have had poorer baseline health and ART compliance than normal children. In reality, HIV affects nutritional status on its own, increasing susceptibility to the virus and hastening disease progression in malnourished children [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Furthermore, stunted children may have had a simultaneous opportunistic infection that caused them to miss out on receiving their medications [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, children whose regimens were not changed were 4.4 times more likely to experience ART treatment failure than were those whose regimens were changed. It is possible that the majority of previous regimens include adverse effects that lead to advanced disease and complications, which can ultimately lead to death. For example, AZT regimens can lead to anaemia, which exacerbates the progression of the disease [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This was further confirmed by the fact that the failure rate prior to 2019 was greater than the rate from 2019 onwards, and children who received NVP-based NNRT had a 2.72-fold greater chance of treatment failure than did those who did not receive nevirapine. This finding was supported by studies conducted in South Africa, [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], Uganda and Tanzania [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. This could be because nevirapine produces adverse symptoms such as rash, nausea, fatigue, fever, headache, vomiting, diarrhea, and abdominal discomfort, which can make it difficult to adhere to a treatment regimen and lead to treatment failure [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Finally, those children who were still treated based on the old guidelines were 1.5 times more likely to experience ART failure than were those who were treated based on the new guidelines. This result was supported by the comprehensive National ART Guidelines 2018. According to the guidelines, due to side effects and treatment failure, nevirapine-based regimens should be changed to DTG regimens containing drugs when the patient ages from 6 weeks to 10 years and the weight\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;20 kg[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, among those children who developed treatment failure, only 37.2% changed their guidelines to new ones. These findings are consistent with the results of the change in regimen and nevirapine-based regimen use. Moreover, for those children with treatment failure, 71.1% were older than or equal to five years, and 73.3% had a viral load\u0026thinsp;\u0026lt;\u0026thinsp;1000 copies/ml. These criteria can be used to guide the new guidelines even though they are not practical. This may be due to inappropriate training given for health professionals or drug shortages.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCompared to the UNAIDS cut-off value of 10%, the prevalence of ART treatment failure (21.2%) in this study area was unacceptably high [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Despite efforts to improve access to ART, the issue of a higher treatment failure rate has recently become a hot topic. Advanced WHO stages, poor adherence to ART, stunting, use of a nevirapine-based regimen, treatment in the old guidelines and no change in regimen were associated with a greater risk of treatment failure. Therefore, continuous and extensive follow-up, strict adherence to the new treatment guidelines, training of ART clinic staff, prospective study design, and investigation of the reasons why the majority of children were put on the old guidelines were recommended.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAHR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Adjusted Hazard Ratio\u003c/p\u003e\n\u003cp\u003eAIDS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Acquired Immune Deficiency Syndrome\u003c/p\u003e\n\u003cp\u003eART \u0026nbsp; \u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Antiretroviral Therapy\u003c/p\u003e\n\u003cp\u003eCPT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cotrimoxazole prophylaxis\u003c/p\u003e\n\u003cp\u003eCD4 \u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cluster of Differentiation 4 cells\u003c/p\u003e\n\u003cp\u003eCHR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Crude hazard ratio\u003c/p\u003e\n\u003cp\u003eHIV \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Human immunodeficiency viruses\u003c/p\u003e\n\u003cp\u003eHAART \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Highly active antiretroviral therapy\u003c/p\u003e\n\u003cp\u003eHAZ \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Height for Age Z score\u003c/p\u003e\n\u003cp\u003eUNICEF\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp; \u0026nbsp; United Nations International Children\u0026rsquo;s Emergency Fund\u003c/p\u003e\n\u003cp\u003eUNAIDS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Joint United Nations Program on HIV/AIDS\u003c/p\u003e\n\u003cp\u003eWAZ \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Weight for Age Z score\u003c/p\u003e\n\u003cp\u003eWHO \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;World Health Organization\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThe protocol was approved by the Research Ethics Committee of the School of Nursing, College of Health Sciences, Addis Ababa University. Waiver of informed consent from individual patients was obtained from the Research Ethics Committee as the study was a retrospective review of medical records. Patient data were collected and analysed unanimously.\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u0026nbsp;Not applicable\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe datasets used and/or analysed 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\u003cp\u003eFunding:we did not receive funding for this work.\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026apos; contributions\u003c/h2\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;AK and ET:\u003c/strong\u003e Substantially contributed to the conception, design, acquisition, analysis, and interpretation of the data and to the drafting and revision of the manuscript. \u003cstrong\u003eMA:\u003c/strong\u003e advised on the study design and data collection and revised the manuscript. All the authors approved the submitted version and agreed both to be personally accountable for the author\u0026rsquo;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eWe would like to express our heartfelt gratitude and appreciation to the study participants, health institutions, \u0026nbsp;health care workers involved in this study and Addis Ababa University.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eUNAIDS. Global HIV statistics, FACT SHEET 2022. Acccedd on Nov; 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEthiopian Public Health Institute. : HIV Related Estimates and Projections in Ethiopiafor the Year 2021\u0026ndash;2022. In. 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The HIV drug optimization agenda: promoting standards for earlier investigation and approvals of antiretroviral drugs for use in adolescents living with HIV. J Int AIDS Soc. 2020;23:e25576.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEndalamaw A, Mekonnen M, Geremew D, Yehualashet FA, Tesera H. Habtewold TDJBph: HIV/AIDS treatment failure and associated factors in Ethiopia: meta-analysis. 2020, 20(1):1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShumetie A, Moges NA, Teshome M, Gedif G. Determinants of Virological Failure Among HIV-Infected Children on First-Line Antiretroviral Therapy in West Gojjam Zone, Amhara Region, Ethiopia. HIV/AIDS (Auckland NZ). 2021;13:1035.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDow DE, Shayo AM, Cunningham CK, Reddy EAJB. Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up. 2014, 14(1):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrooks AD, Sanoski C, Hajjar ER, Overholser BR. Naplex 2017 Strategies, Practice \u0026amp; Review with 2 Practice Tests: Online\u0026thinsp;+\u0026thinsp;Book. Simon and Schuster; 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZenebe E, Washo A, Addis Gesese A. Time to First-Line Antiretroviral Treatment Failure and Its Predictors among HIV-Positive Children in Shashemene Town Health Facilities, Oromia Region, Ethiopia, 2019. \u003cem\u003eScientificWorldJournal\u003c/em\u003e 2021, 2021:8868479.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCostenaro P, Penazzato M, Lundin R, Rossi G, Massavon W, Patel D, Nabachwa S, Franceschetto G, Morelli E, Bilardi D. Predictors of treatment failure in HIV-positive children receiving combination antiretroviral therapy: cohort data from Mozambique and Uganda. J Pediatr Infect Dis Soc. 2015;4(1):39\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYassin S, Gebretekle GB. Magnitude and predictors of antiretroviral treatment failure among HIV-infected children in Fiche and Kuyu hospitals, Oromia region, Ethiopia: a retrospective cohort study. Pharmacol Res Perspect. 2017;5(1):e00296.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMutwa PR, Boer KR, Asiimwe-Kateera B, Tuyishimire D, Muganga N, Lange JM, van de Wijgert J, Asiimwe A, Reiss P, Geelen SP. Safety and effectiveness of combination antiretroviral therapy during the first year of treatment in HIV-1 infected Rwandan children: a prospective study. PLoS ONE. 2014;9(11):e111948.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSebunya R, Musiime V, Kitaka SB, Ndeezi G. Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. AIDS Res therapy. 2013;10(1):1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEmmett SD, Cunningham CK, Mmbaga BT, Kinabo GD, Schimana W, Swai ME, Bartlett JA, Crump JA, Reddy EA. Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: a cross-sectional study. J Acquir Immune Defic Syndr. 2010;54(4):368.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar P. Adult pulmonary tuberculosis as a pathological manifestation of hyperactive antimycobacterial immune response. Clin Translational Med. 2016;5(1):1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZoufaly A, Fillekes Q, Hammerl R, Nassimi N, Jochum J, Drexler JF, Awasom CN, Sunjoh F, Burchard GD, Burger DMJAT. Prevalence and determinants of virological failure in HIV-infected children on antiretroviral therapy in rural Cameroon: a cross-sectional study. 2013, 18(5):681\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMakadzange A, Higgins-Biddle M, Chimukangara B, Birri R, Gordon M, Mahlanza T, McHugh G, Van Dijk J, Bwakura-Dangarembizi M. Ndung\u0026rsquo;u TJPO: Clinical, virologic, immunologic outcomes and emerging HIV drug resistance patterns in children and adolescents in public ART care in Zimbabwe. 2015, 10(12):e0144057.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFederal H, Prevention A. Control Office Federal Ministry of Health. \u003cem\u003eGuidelines for prevention of mother-to-child transmission of HIV in Ethiopia\u003c/em\u003e 2007.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNegese D, Addis K, Awoke A, Birhanu Z, Muluye D, Yifru S, Megabiaw B. HIV-positive status disclosure and associated factors among children in North Gondar, Northwest Ethiopia. \u003cem\u003eInternational Scholarly Research Notices\u003c/em\u003e 2012, 2012.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavies M-A, Moultrie H, Eley B, Rabie H, Van Cutsem G, Giddy J, Wood R, Technau K, Keiser O, Egger M. Virologic failure and second-line antiretroviral therapy in children in South Africa-The IeDEA Southern Africa Collaboration. \u003cem\u003eJournal of acquired immune deficiency syndromes (\u003c/em\u003e1999\u003cem\u003e)\u003c/em\u003e 2011, 56(3):270.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamya MR, Mayanja-Kizza H, Kambugu A, Bakeera-Kitaka S, Semitala F, Mwebaze-Songa P, Castelnuovo B, Schaefer P, Spacek LA, Gasasira AF. Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. JAIDS J Acquir Immune Defic Syndr. 2007;46(2):187\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrganization WH. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. World Health Organization; 2016.\u003c/span\u003e\u003c/li\u003e\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":"Incidence, Predictors, ART treatment failure, Ethiopia","lastPublishedDoi":"10.21203/rs.3.rs-3887288/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3887288/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHuman immunodeficiency virus (HIV) infection is still a major health problem in children in Ethiopia. Even though there is a rapid scale-up of antiretroviral therapy (ART), information on pediatric treatment failure is limited in the country. Hence, this study was designed to assess the incidence and predictors of ART treatment failure among children who were receiving first-line ART in East Gojjam, Ethiopia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA fifteen-year retrospective follow-up study was conducted among 538 randomly selected under-15-year-old children who started antiretroviral medication between September 11, 2006, and September 10, 2021, in multicentre health facilities in East Gojjam. The medical records of the study participants were reviewed, and the required data were extracted using pretested structured checklists. The data were entered and cleaned using SPSS version 25 and exported to STATA version 14 for further statistical analysis. The Kaplan‒Meier survival curve, the log-rank test, and the scaled Schoenfeld residual test were applied for analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFrom a total of 538 medical records of children receiving antiretroviral treatment reviewed, 114 (21.2%) (95% CI: 17.8\u0026ndash;24.9) developed treatment failure, 85 (74.6%) were virological, 19 (16.7%) were immunological (CD4), and 10 (8.8%) were clinical failures. The overall incidence density of treatment failure was 4.53 per 1000 person-months, with a mean survival time of 43.8 months (95% CI\u0026thinsp;=\u0026thinsp;37.65\u0026ndash;50.89) at treatment failure. WHO clinical stage III/IV (AHR\u0026thinsp;=\u0026thinsp;3.0, CI\u0026thinsp;=\u0026thinsp;1.3, 7.1), regimen not changed (AHR\u0026thinsp;=\u0026thinsp;4.4, CI\u0026thinsp;=\u0026thinsp;1.7, 11.7), poor ART adherence (AHR\u0026thinsp;=\u0026thinsp;6.6, CI\u0026thinsp;=\u0026thinsp;4.11, 10.66), stunting (AHR\u0026thinsp;=\u0026thinsp;2.2, CI\u0026thinsp;=\u0026thinsp;1.43, 3.44), and nevirapine containing regimen (AHR\u0026thinsp;=\u0026thinsp;2.72, CI\u0026thinsp;=\u0026thinsp;1.13\u0026ndash;6.54) were significant predictors of treatment failure.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe incidence of ART treatment failure among the study participants was significantly high. WHO clinical stage III/IV, poor adherence to ART, regimen not changed, and nevirapine-containing regimen were all significant predictors of ART failure. Hence, by providing intensive care and close monitoring to higher-risk patients, a timely change in regimen was recommended.\u003c/p\u003e","manuscriptTitle":"Incidence and Predictors of Treatment Failure Among Children Receiving First-Line Antiretroviral Therapy in East Gojjam, Ethiopia: A Fifteen-year Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-29 16:26:24","doi":"10.21203/rs.3.rs-3887288/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":"31359d75-1605-40d7-b20f-27c4af126f01","owner":[],"postedDate":"January 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-01T11:08:48+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-29 16:26:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3887288","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3887288","identity":"rs-3887288","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}