Abstract
Background
Studies have shown a high rate of mortality among adults despite the introduction of highly active antiretroviral therapy (HAART). However, long-term outcomes of HAART among children remain poorly documented in Ethiopia. This study aimed to estimate the survival rate and identify associated factors among HIV-infected children on antiretroviral therapy.
Methods
A retrospective cohort study was conducted from August to December 2022 in 13 health facilities (HFs) using records of 554 children (<15 years old) initiating HAART from 2007 to 2019. HFs were selected using probability proportional to the size of patients. Survival rate and predictors of mortality were estimated using Kaplan-Meier and Cox-proportional hazards, respectively. The analysis was done using STATA V.16.0.
Result
Overall mortality among HIV-positive children taking HAART in Ethiopia in 12-year follow-up was 25.5%. Moreover, the mortality rate was 24 per 100 child-year observation. Survival during the median 9.65 (95% CI=9.30 to 10.00) years of follow-up was 0.50. There was a significant drop in the survival rate from the 6th year of follow-up (0.96) to the 8th year (0.78) till the 12th year (0.18). By the end of the follow-up period, 172 (23.69%) were lost to follow-up. There was a high risk of mortality among female (adjusted HRs (AHRs) (95% CI) =1.35 (1.14 to 1.65)), those with poor adherence (AHR (95% CI) =1.29 (1.13 to 1.35)), CD4 count of ≤200 cells/mm3 (AHR (95% CI) =1.75 (1.33 to 2.30)) and baseline haemoglobin≤12 g/dL (AHR (95% CI) =1.8 (1.66 to 1.98)).
Conclusion
The significant drop in the survival rate as of the 6th year follow-up and the high loss rate to follow-up call for programme attention. Close follow-up of children with low CD4 count, low haemoglobin and poor adherence could help improve survival.
Keywords: Mortality, HIV
WHAT IS ALREADY KNOWN ON THIS TOPIC
While highly active antiretroviral therapy (HAART) has reduced mortality in adults, long-term outcomes for children with HIV, especially in Ethiopia, remain poorly understood, with limited data on survival trends and risk factors.
WHAT THIS STUDY ADDS
This study reports a 25.5% mortality rate over 12 years among HIV-positive children on HAART, with a notable decline in survival after 6 years. Factors such as female gender, poor adherence, low CD4 count and anaemia were strongly linked to higher mortality.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The findings highlight the need for improved long-term follow-up care and targeted interventions for children at risk, particularly those with poor adherence,low CD4 count and Hgb value, which could shape future research and health policies for paediatric HIV care in Ethiopia.
Background
HIV infection remains one of the major global public health challenges, with a higher burden in low-income and middle-income countries. Nearly 90% of the world’s HIV-infected children are living in sub-Saharan Africa.1 In Ethiopia, an estimated 88 000 children are living with HIV out of the estimated 18 million children under the age of 15 years old during the year 2016, more than 15 000 children died because of AIDS-related causes.2 Thus, approximately 17.05% of children living with HIV in Ethiopia died from AIDS-related causes in 2016. It has been shown that with the current availability of highly active antiretroviral therapy (HAART), HIV-associated mortality and morbidity among children significantly reduced,3 and consequently, a drastic decrease in hospitalisations and deaths. HAART has provided survival advantages to children with HIV infection.4 Since 2005, Ethiopia has been scaling up access to HAART for people living with HIV (PLHIV), and a significant improvement was reported in the quality of life and survival rates among children in Ethiopia.5 6
Studies show that this early access to HAART can potentially prevent 25% of HIV-related deaths.7 Comprehensive treatment, care and support for HIV-infected children are, therefore, essential in reducing child mortality due to HIV/AIDS.8,10 Ethiopia has adopted the initiation of HAART for all HIV-infected patients, irrespective of the CD4 cell count, that was recommended by the WHO, as part of the strategy of reducing HIV-related morbidity and mortality11 as a result of which the number of HAART sites increased from three to more than 1000 between 2006 and 2016, and the number of adults on HAART increased from 24 000 to 308 000. More than 23 400 children received antiretroviral medications during that period.12 Increased access to HAART has improved survival among HIV-positive children in Ethiopia and other sub-Saharan countries.13,15 However, reports from Kenya, Zambia and Malawi indicate that mortality among HIV-positive children after HAART initiation remains high, ranging from 7.5% to 21%.16 17 This is in contrast to the significantly higher survival rates observed among HIV-positive children who begin HAART in developed countries. Studies among children on HAART from Africa and other low-income countries showed that, though HAART programmes had reduced mortality, it was often associated with a very low CD4 count, advanced illness based on WHO staging, low haemoglobin levels and opportunistic infections.9 18 19
However, there is still inconclusive evidence regarding the survival of children on HAART in Ethiopia, and little information is available on the determinants of mortality among this population.3 17 20 21 Therefore, this study aimed to estimate survival time and identify predictors of mortality among children infected with HIV on HAART in Ethiopia.
Method
This was a retrospective cohort study conducted from August to December 2022 among children (<15 years old) taking HAART in Ethiopia, which was part of the national study ‘HIV-1 treatment failure among PLHIV in Ethiopia’. For the initial study, a total of 63 health facilities (HFs) were included considering 11 751 (11 013 adults and 738 children) study participants (figure 1). As part of this substudy, we identified 13 of the HFs that had paediatric HIV care and treatment facilities, and we retrieved data from children taking HAART who were attending from 2007 to 2019. Clinical and laboratory data were captured from the participant’s medical records, since the initiation of HAART (1 January 2007) till 31 December 2019.
Figure 1. Sampling and sample size determination for the survival analysis among HIV-positive children in Ethiopia using the available data.
The source population for this study was children less than 15 years old by the end of the follow-up period and who were on first-line HAART in Ethiopia. Those children who had incomplete medical record for the outcome (functional status) during the end of the follow-up period were excluded while lost to follow-up were followed-up until the time reported as lost.
Sampling size determination
For this analysis, we first calculated the required sample size, evaluated it with the available data from the initial study. The required sample size was also estimated from a previous study in Ethiopia that provided event rates for children on HAART. Accordingly, the proportion of children with CD4 counts less than 200 cells/µL (considered immunocompromised) who experience the event of interest (death) was labelled as p1 (0.084). Moreover, taking the proportion of children with CD4 counts greater than or equal to 200 cells/µL (considered immunocompetent) who experience the same event of interest p2 (0.047).20 Taking the desired power and significance levels as (0.80) and (0.05), respectively, and with a 10% incomplete record using the formula below which has a similar assumption with the online available calculator from Open Epi: (https://www.openepi.com/SampleSize/SSCohort.htm), the total sample size required for our study was 777 participants.
Accordingly, the calculated sample size was 94.89% consistent with the available data for children taking HAART in Ethiopia.
Variables of the study
Independent variables include
Demographic characteristics of the children including gender, age and residency (urban vs rural). Individual risk factors such as CD4 count (≤200 cells/mm3 vs >200 cells/mm3), haemoglobin levels (≤12 mg/dL vs >12 mg/dL) and WHO clinical stage (stages I–IV) were considered as independent variables. Finally, adherence to HAART was evaluated using self-reported questionnaires, where adherence levels were classified as good, moderate or poor based on missed doses in 30 days. Functional status at baseline was also considered based on whether the child was ambulatory or bedridden. Treatment interruption history and exposure to HAART before initiation were also examined as independent variables. Urban dwellers: refers to individuals residing in cities or towns that are classified as urban areas according to Ethiopian government definitions. These areas typically feature higher population densities, greater access to healthcare facilities, educational institutions and economic opportunities compared with rural areas.
Dependent variables
The primary dependent variable was functional status at the end of the follow-up, which was categorised as either alive or dead.
Data collection and processing
Data were collected from medical record registers and electronic records acquired from the Ethiopian Ministry of Health at HAART. Three registers were available: The first registry was the pre-ART registry, which recorded all confirmed HIV-positive patients who visited the clinics. Then, all children who started treatment HAART were transferred to the HAART registry on the day they started treatment. The third registry was the patients’ follow-up form. For each child, the first follow-up visit was scheduled every 2 weeks after the start of treatment, and then the medical records were updated at each follow-up visit, depending on the patient’s adherence (ie, the extent to which patients follow their prescribed treatment regimens, including taking medications as directed). There was an electronic medical record that contained the entire medical history of the HIV-positive patients since the determination of positivity. Data retrieved included clinical characteristics and laboratory results, as well as WHO clinical stage, CD4 counts, haemoglobin, HAART regimens, medications and functional status (alive or dead). In addition, data were collected on demographic characteristics (age, sex, marital status, education level and occupation) and individual factors (medication adherence).
Data collectors and caregivers working in the selected HFs received training in data management. The procedure was controlled by the study director. Completed data collection instruments were checked for completeness and consistency. Data from the records were entered into a previously created data entry screen (CSPro) using tablet computers.
Patient and public involvement
No patient involved.
Statistical analysis
Children’s characteristics were described in terms of frequency, median and IQR for continuous data and percentages for categorical data. Continuous variables were also compared with t-tests or rank sum tests after checking the normality of the distribution with the Shapiro-Wilk test. The date of initiation of HAART treatment and the date of outcome (alive or death) were used as the start and end points, respectively, of the follow-up period. Children who were alive and on treatment were censored from the date of their last clinic visit. Data analysis was performed for each of the cohorts according to their calendar year. Follow-up time was calculated from the date of onset of HAART to the date of death or censoring. Kaplan-Meier analysis was performed to estimate the survival rate of study participants. Cox-proportional hazard regression was calculated to identify significant factors associated with survival. We used both crude and adjusted HRs with 95% CIs and candidate variables with p<0.2 were included in the multivariable Cox-regression model. Independent variables with values of <0.05 within the multivariable Cox-regression model were considered statistically significant predictors of mortality. The proportional hazards assumption was tested by both graphical and statistical tests of goodness of fit (Schoenfeld method). All data analyses were performed using STATA V.16.0 for each of the cohorts.
Result
Baseline characteristics
From the total of 554 children aged below 15 years enrolled in this study, 279 (50.4%) were boy, and the majority, 497 (89.7%), were urban dwellers. The age of the cohorts at HAART initiation ranged from 3 to 168 months, with a median age of 72 months (IQR=33–108). The majority were aged 7–11 years, followed by 12–15 years, accounting for 46.8% and 31.8%, respectively (table 1).
Table 1. Baseline characteristics of children taking HAART in Ethiopia (2007–2019).
| Variable | Frequency | Percent |
| Gender | ||
| Female | 275 | 49.6 |
| Male | 279 | 50.4 |
| Residency | ||
| Urban | 497 | 89.7 |
| Rural | 57 | 10.3 |
| Education status | ||
| No formal education | 43 | 7.8 |
| Primary school education | 444 | 80.1 |
| secondary/high school education | 67 | 12.1 |
| Don't know | 106 | 19.1 |
| Exposure to HAART before initiation | ||
| Yes | 10 | 1.8 |
| No | 544 | 98.2 |
| Is the child an orphan? | ||
| Yes | 159 | 28.7 |
| No | 395 | 71.3 |
| Does the child miss an appointment (in the last 4 weeks)? | ||
| Yes | 54 | 9.7 |
| No | 500 | 90.3 |
| Type of HAART | ||
| ABC+3TC+EFV | 9 | 1.6 |
| ABC+3TC+LPV/r | 1 | 0.2 |
| ABC+3TC+NVP | 1 | 0.2 |
| AZT+3TC+EFV | 77 | 13.9 |
| AZT+3TC+LPV/r | 2 | 0.4 |
| AZT+3TC+NVP | 198 | 35.7 |
| d4t+3TC+EFV | 25 | 4.5 |
| d4t+3TC+NVP | 169 | 30.5 |
| TDF+3TC+EFV | 35 | 6.3 |
| TDF+3TC+NVP | 2 | 0.4 |
| HAART substitution | ||
| No | 288 | 52.0 |
| Yes | 266 | 48.0 |
| Total | 554 | 100.0 |
ABCAbacavirEFVEfavirenzHAARThighly active antiretroviral therapyLPV/rLopinavir/ritonavir3TCLamivudine
Clinical outcomes
Out of the children taking HAART, 525 (94.8%) were ambulatory, while the remaining 29 (5.2%) were bedridden at baseline. By the end of the follow-up, 413 (74.5%) remained ambulatory, while 141 (25.5%) had died. At the study baseline, 250 (43.3%) of the participants were at WHO clinical stage III or IV, which improved to 62 (11.2%) by the end of the follow-up. Regarding adherence, 7 (1.3%) had poor adherence at baseline, increasing to 30 (5.4%) at the end of the follow-up. Baseline viral load suppression was 344 (62.1%), which improved to 454 (81.9%). In terms of CD4 count, 121 (21.8%) had a baseline CD4 count of ≤200 cells/mm³, which improved to 44 (7.9%). By the end of the follow-up year, 172 (23.69%) were lost to follow-up (figure 2).
Figure 2. Clinical outcome among children taking highly active antiretroviral therapy in Ethiopia (2007–2019).
Mortality
Mortality among HIV-positive children taking HAART in Ethiopia over 12-year follow-up was 25.5%, with a mortality rate of 24 per 100 child-years. By the end of the follow-up, mortality among children in rural areas was 38.6%, compared with 23.94% in urban Ethiopia. Mortality was higher among those with no education (38.60%) compared with those attending secondary school (17.91%). Among children with a history of treatment interruption, mortality was 39.29%, while it was 24.7% among those without this history (table 2).
Table 2. Mortality among children taking HAART in Ethiopia (2007–2019).
| Variable | Functional status | Mortality (%) | Total | |
| Alive | Death | |||
| Gender | ||||
| Female | 195 | 80 | 29.09 | 275 |
| Male | 218 | 61 | 21.86 | 279 |
| Residency | ||||
| Urban | 378 | 119 | 23.94 | 497 |
| Rural | 35 | 22 | 38.60 | 57 |
| Education status | ||||
| No formal education | 26 | 17 | 39.53 | 43 |
| Primary school education | 332 | 112 | 25.23 | 444 |
| secondary/high school education | 55 | 12 | 17.91 | 67 |
| Child treatment interruption | ||||
| Yes | 17 | 11 | 39.29 | 28 |
| No | 396 | 130 | 24.71 | 526 |
| Child missed appointment | ||||
| Yes | 17 | 6 | 26.09 | 23 |
| No | 396 | 135 | 25.42 | 531 |
| Overall facility service delivery | ||||
| Excellent | 53 | 26 | 32.91 | 79 |
| Very good | 188 | 66 | 25.98 | 254 |
| Good | 166 | 47 | 22.07 | 213 |
| Satisfactory | 3 | 1 | 25.00 | 4 |
| Unsatisfactory | 3 | 1 | 25.00 | 4 |
| Is the child orphan? | ||||
| Yes | 118 | 41 | 25.79 | 159 |
| No | 295 | 100 | 25.32 | 395 |
| Type of HAART | ||||
| ABC, 3TC, EFV | 9 | 0 | 0.00 | 9 |
| ABC, 3TC, LPV/r | 0 | 1 | 100.00 | 1 |
| ABC, 3TC, NVP | 0 | 1 | 100.00 | 1 |
| AZT, 3TC, EFV | 57 | 20 | 25.97 | 77 |
| AZT, 3TC, LPV/r | 1 | 1 | 50.00 | 2 |
| AZT, 3TC, NVP | 138 | 60 | 30.30 | 198 |
| d4t, 3TC, EFV | 17 | 8 | 32.00 | 25 |
| d4t, 3TC, NVP | 132 | 37 | 21.89 | 169 |
| TDF, 3TC, EFV | 27 | 8 | 22.86 | 35 |
| TDF, 3TC, NVP | 2 | 0 | 0.00 | 2 |
| HAART substitution | ||||
| No | 209 | 79 | 27.43 | 288 |
| Yes | 204 | 62 | 23.31 | 266 |
| Functional status (baseline) | ||||
| Ambulatory | 390 | 135 | 25.71 | 525 |
| Bedridden | 23 | 6 | 20.69 | 29 |
| Age (year) | ||||
| ≤1 | 1 | 0 | 0.00 | 1 |
| 2–6 | 87 | 35 | 28.69 | 122 |
| 7–11 | 199 | 60 | 23.17 | 259 |
| 12–15 | 126 | 46 | 26.74 | 172 |
| Total | 413 | 141 | 25.45 | 554 |
ABCAbacavirAZTZidovudined4tStavudineEFVEfavirenzHAARThighly active antiretroviral therapyLPV/rLopinavir/ritonavirNVPNevirapine3TCLamivudine
Impact of baseline clinical parameters on mortality
Among those with poor adherence during HAART initiation, 42.86% died, compared with 25.83% among those with good adherence. Mortality among children with a CD4 count≤200 cells/mm3 was 42.15%, compared with 20.79% among their counterparts. Mortality among virally suppressed children at HAART initiation was 36.00%, while it was 28.20% among those virally suppressed during follow-up (figure 3).
Figure 3. Impact of baseline clinical parameters on mortality among HIV-positive children in Ethiopia. Hgb, haemoglobin.

Survival
The survival rate of children on HAART in Ethiopia over a mean of 9.65 years (95% CI=9.30 to 10.00) of follow-up was 0.502. The mean survival rate of children living with HIV who were taking HAART during 2007–2019 in the first 2-year follow-up was 0.998 (95% CI=0.590 to 1.0) and 0.987 (95% CI=0.60 to 1.0), respectively. There was a significant drop in the survival rate from the 6th year of follow-up 0.96 to the 8th year 0.78 until the 12th year 0.18 (figure 4).
Figure 4. Survival among children taking highly active antiretroviral therapy (HAART) in Ethiopia. (A) Kaplan-Meier curve for the cumulative survival. (B) Probability of survival over the 12-year follow-up.
Predictors of mortality
The risk of mortality was higher among female children, those with poor adherence, a CD4 count of ≤200 cells/mm3, baseline haemoglobin≤12 mg/dL and those who were bedridden, with adjusted HRs (AHRs) of 1.35 (95% CI=1.14 to 1.65), 1.29 (95% CI=1.13 to 1.35), 1.75 (95% CI=1.33 to 2.30), 1.8 (95% CI=1.66 to 1.98) and 8.44 (95% CI=5.51 to 11.39), respectively (table 3).
Table 3. Predictors of mortality among children taking HAART in Ethiopia (2007–2019).
| Sig. | CHR | 95.0% CI | Sig. | AHR | 95.0% CI | |||
| Lower | Upper | Lower | Upper | |||||
| Gender | ||||||||
| Female | 0.029 | 0.805 | 0.663 | 0.978 | 0.003 | 1.349 | 1.106 | 1.645 |
| Male | Ref. | |||||||
| Residency | ||||||||
| Urban | 0.154 | 1.292 | 0.909 | 1.836 | ||||
| Rural | Ref. | |||||||
| Education status | ||||||||
| No formal education | Ref. | |||||||
| Primary school education | 0.947 | 0.984 | 0.610 | 1.588 | ||||
| Secondary/high school education | 0.955 | 1.009 | 0.747 | 1.363 | ||||
| Exposure to HAART before initiation | ||||||||
| Yes | 0.618 | 0.797 | 0.327 | 1.943 | ||||
| No | Ref. | |||||||
| Child treatment interruption | ||||||||
| Yes | 0.374 | 0.782 | 0.456 | 1.344 | ||||
| No | Ref. | |||||||
| Child missed appointment | ||||||||
| Yes | 0.644 | 1.149 | 0.637 | 2.074 | ||||
| No | Ref. | |||||||
| Is the child an orphan? | ||||||||
| Yes | 0.445 | 0.919 | 0.738 | 1.143 | ||||
| No | Ref. | |||||||
| Does the child miss an appointment? | ||||||||
| Yes | 0.311 | 0.820 | 0.559 | 1.203 | ||||
| No | Ref. | |||||||
| HAART substitution | ||||||||
| Yes | 0.043 | 1.215 | 0.998 | 1.480 | 0.224 | 1.140 | 0.923 | 1.407 |
| No | Ref. | |||||||
| Functional status (baseline) | ||||||||
| Ambulatory | Ref. | |||||||
| Bedridden | 0.142 | 1.392 | 0.896 | 2.163 | 0.02 | 8.44 | 5.512 | 11.392 |
| WHO clinical stage (baseline) | ||||||||
| I | 0.041 | |||||||
| II | 0.058 | 1.536 | 0.985 | 2.395 | ||||
| III | 0.103 | 1.423 | 0.931 | 2.175 | ||||
| IV | Ref. | |||||||
| Adherence (baseline) | ||||||||
| Good | Ref. | |||||||
| Fair | 0.024 | 0.316 | 0.117 | 0.857 | ||||
| Poor | 0.029 | 0.496 | 0.172 | 1.437 | 0.008 | 1.29 | 1.13 | 1.35 |
| CD4 count (baseline) | ||||||||
| ≤200 | 0.000 | 0.593 | 0.455 | 0.772 | 0.000 | 1.753 | 1.333 | 2.304 |
| >200 | Ref. | |||||||
| Viral suppression (baseline) | ||||||||
| Suppressed | 0.243 | 0.882 | 0.715 | 1.089 | ||||
| Not suppressed | Ref. | |||||||
| Type of HAART | ||||||||
| ABC, 3TC, EFV | 0.010 | 0.072 | 0.010 | 0.539 | ||||
| ABC, 3TC, NVP | 0.004 | 0.456 | 0.269 | 0.773 | ||||
| AZT, 3TC, EFV | 0.760 | 0.883 | 0.398 | 1.960 | ||||
| d4t, 3TC, NVP | 0.000 | 0.383 | 0.257 | 0.570 | ||||
| TDF, 3TC, EFV | Ref. | |||||||
| Hgb (baseline) | ||||||||
| ≤12 | 0.067 | 1.203 | 0.987 | 1.466 | 0.032 | 1.806 | 1.662 | 1.982 |
| >12 | Ref. | |||||||
AHRadjusted HRHAARThighly active antiretroviral therapyHgbhaemoglobin
Discussion
In this study, we observed an overall mortality rate of 25.5% among HIV-positive children on HAART in Ethiopia over a 12-year follow-up period, equating to 24 deaths per 100 person-years. The survival rate during the mean follow-up time of 9.65 years (95% CI: 9.30 to 10.00) was 50.2%. Notably, there was a significant drop in the survival rate from 96.0% in the 6th year of follow-up to 78.0% at the 8th year, further declining to 18.0% by the 12th year. The risk of mortality was higher among girls, children with poor adherence, those with a CD4 count of ≤200 cells/mm3, haemoglobin levels≤12 mg/dL and those who were bedridden at baseline.
The mortality rate of 24 per 100 person-years (25.5%) in this study was higher compared with previous reports in Ethiopia, which documented rates of 4.0 and 16.85 per 100 person-years.20 22 This difference may be due to the extended follow-up period of our study and the increased risk of mortality at advanced stages of HAART. Additionally, differences in study settings and periods may have contributed to this variation. The survival rate observed in our study was consistent with findings from similar studies conducted in Zimbabwe and South Africa.23 24 The mean survival rates of children on HAART during the first 2-year follow-up were 99.5% (95% CI: 59.0 to 100.0) and 99.1% (95% CI: 60.0 to 100.0), respectively, during the period from 2007 to 2019. These results may reflect improvements in early diagnosis of children as part of the prevention of mother-to-child transmission programmes.18 25 26
The significant drop in survival rates from the 6th to the 12th year may be attributed to long-term exposure to HAART, potential drug resistance and immunosuppression, which could lead to increased mortality.27,29 Over the 12-year follow-up, mortality was higher among children in rural areas (38.6%) compared with urban areas (23.94%), consistent with a study conducted at Black Lion Hospital in Addis Ababa.30 Additionally, mortality was higher among children with no education (38.60%) compared with those attending secondary school (17.91%), potentially linked to differences in knowledge, attitudes and practices related to HIV/AIDS and HAART.
Mortality was also higher among children with a history of treatment interruption (39.29%) compared with those without such a history (24.7%), likely due to the increased risk of drug resistance and subsequent death.31 Approximately 42.86% of children with poor adherence at baseline died during the follow-up period. This finding aligns with reports that HAART-related medication adherence is a critical challenge and a predictor of mortality among children.1932,34 Mortality among children with a baseline CD4 count of ≤200 cells/mm3 was 42.15%, highlighting the impact of immunosuppression on mortality in this population.21 34 35
Despite significant progress in scaling up HAART, challenges related to the loss of follow-up and early mortality remain.36 The average retention (ie, the continued participation of children in care over time, particularly their sustained engagement with regular visits to ART clinics as per the schedule) in care reported in other studies conducted in Ethiopia was 92%, ranging from 67% to 100%.37 In our analysis, the loss to follow-up among children was 23.69%, equivalent to a retention rate of 76.31%. This retention rate is higher than that reported in studies from Tanzania (54%) and Cameroon (20%).38 39 Literature suggests that defaulter tracing and adherence support could improve patient retention. Our study’s retention rate was also higher than that reported in other studies conducted in Cameroon (69.2%),39,45 which may be due to methodological and population differences.
The risk of mortality among female children was 1.35 times higher (95% CI: 1.14 to 1.65) than among male children. Children whose parents were dissatisfied with HAART services were at 18.2 times higher risk of mortality (95% CI: 3.44 to 96.69) compared with those whose parents were satisfied with service delivery, potentially due to factors affecting adherence and treatment outcomes.46 47 Children with poor adherence had a 1.29 times higher risk of mortality (95% CI: 1.13 to 1.35) compared with those with good adherence, consistent with other studies.16 22 31 44 45 Children with a baseline CD4 count of ≤200 cells/mm3 were at 1.75 times higher risk of mortality (95% CI: 1.33 to 2.30) compared with those with a CD4 count>200 cells/mm3, consistent with previous studies on CD4 count as a predictor of survival.11 46 47 Additionally, children with a baseline haemoglobin level of ≤12 mg/dL were at 1.8 times higher risk of mortality (95% CI: 1.66 to 1.98) compared with those with haemoglobin levels>12 mg/dL, consistent with findings from studies conducted at Armed Forces Hospital, Addis Ababa, Ethiopia, and in Brazil.43 44
Although we accounted for loss to follow-up in our sample size calculation, it is possible that some of the children lost to follow-up may have died, potentially leading to an underestimation of our findings.
Limitation
As a retrospective cohort study, our findings are inherently subject to biases associated with this design. A significant percentage of participants (23.69%) were lost to follow-up during the study period, which may introduce selection bias. Those who did not continue care may differ substantially from those who remained in the study, leading to an underestimation of the true mortality risk among HIV-infected children on HAART. Furthermore, treatment adherence was assessed through self-reporting of missed doses, which can be subject to recall bias and social desirability bias. Participants may underreport missed doses to appear more adherent, resulting in an overestimation of adherence levels. The study was conducted in 13 HFs across Ethiopia, which may limit the generalisability of our findings to other regions or healthcare settings. Additionally, while our study emphasises survival and mortality predictors, the absence of detailed data on opportunistic infections limits our understanding of the complex interplay between opportunistic infections (OIs) and treatment outcomes. Despite these limitations, our study provides valuable insights into the long-term survival of HIV-infected children on HAART in Ethiopia. Future research should focus on prospective designs and more comprehensive data collection methods to validate and expand on our findings.
Conclusion
This study highlights the significant long-term mortality risk among HIV-positive children on HAART in Ethiopia, with a sharp decline in survival after 6 years of treatment. Key factors contributing to higher mortality include poor adherence, low baseline CD4 count, female gender and rural residence. Despite advances in early diagnosis and HAART access, retention in care remains a challenge among children taking HAART in Ethiopia. This finding underscores the need for targeted interventions to improve adherence and address barriers to long-term care, ultimately aiming to reduce mortality and improve survival outcomes for HIV-positive children in Ethiopia.
Acknowledgements
The authors are grateful to the Ethiopian Public Health Institute. The authors would like to express their special thanks to all data collectors.
Footnotes
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Patient consent for publication: Not applicable.
Ethics approval: This study involves human participants. "The ethical approval was obtained as part of HIV-1 treatment failure and acquired drug resistance among first-line antiretroviral experienced patients in Ethiopia’ from the Ethiopian Public Health Institute Scientific and Ethical Review Office with approval number; EPHI-613/505. Participants gave informed consent to participate before taking part in the study".
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.
Data availability statement
Data are available on reasonable request.
References
- 1.Bisson GP, Gaolathe T, Gross R, et al. Overestimates of survival after HAART: implications for global scale-up efforts. PLoS ONE. 2008;3:e1725. doi: 10.1371/journal.pone.0001725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.FHAPCO HIV/AIDS national strategic plan for Ethiopia, 2021-2025. :2546.
- 3.Poorolajal J, Hooshmand E, Mahjub H, et al. Survival rate of AIDS disease and mortality in HIV-infected patients: a meta-analysis. Public Health (Fairfax) 2016;139:3–12. doi: 10.1016/j.puhe.2016.05.004. [DOI] [PubMed] [Google Scholar]
- 4.Shaik RA, Holyachi SK, Ahmad MS, et al. Clinico-demographic and survival profile of people living with HIV on antiretroviral treatment. Front Public Health. 2023;11:1084210. doi: 10.3389/fpubh.2023.1084210. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- 5.Taha TE. Mother-to-child transmission of HIV-1 in sub-Saharan Africa: past, present and future challenges. Life Sci. 2011;88:917–21. doi: 10.1016/j.lfs.2010.09.031. [DOI] [PubMed] [Google Scholar]
- 6.Clavel F, Hance AJ. HIV Drug Resistance. N Engl J Med. 2004;350:1023–35. doi: 10.1056/NEJMra025195. [DOI] [PubMed] [Google Scholar]
- 7.Jonas A, Sumbi V, Mwinga S, et al. HIV drug resistance early warning indicators in namibia with updated World Health Organization guidance. PLoS One. 2014;9:e100539. :e100539. doi: 10.1371/journal.pone.0100539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Tegiste Assefa EW. Survival analysis of patients under chronic HIV-care and antiretroviral treatment at Tikur Anbessa Specialized. Ethiop J Heal Dev. 2012;26:22–9. [Google Scholar]
- 9.Mengesha S, Belayihun B, Kumie A. Predictors of Survival in HIV-Infected Patient after Initiation of HAART in Zewditu Memorial Hospital, Addis Ababa, Ethiopia. Int Sch Res Notices. 2014;2014:1–6. doi: 10.1155/2014/250913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Wondifraw Baynes H, Tegene B, Gebremichael M. Assessment of the effect of antiretroviral therapy on renal and liver functions among hiv-infected patients: A retrospective study. HIV/AIDS Res Palliat Care. 2017;9:1–7. doi: 10.2147/HIV.S120979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Dare DJ. HIV antiretroviral therapy in overcoming implementation challenges. 2007
- 12.FMOH Ethiopia . FMOH; 2018. National consolidated guidelines for comprehensive HIV prevention, care and treatment; pp. 1–238.https://hivpreventioncoalitionhivpreventioncoalition.unaids.org/en/resources/ethiopia-national-consolidated-guidelines-comprehensive-hiv-prevention-care-and-treatment Available. [Google Scholar]
- 13.F. D. Republic Country progress report on the HIV. 2014
- 14.Edén A. HIV persistence and viral reservoirs. 2010
- 15.H. I. V Treatment Global update on HIV treatment 2013. 2013
- 16.Deres G, Mehari Nigussie Z, Genetu Chanie M, et al. Survival Time and Associated Factors Among Adults Living with HIV After Initiation of HAART in South Gondar, Northwest Ethiopia: A Retrospective Cohort. J Multidiscip Healthc. 2021;14:1463–74. doi: 10.2147/JMDH.S314004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Gebrie Getu A, Zelalem Mehari N. Survival time and its predictors among HIV-infected children after antiretroviral therapy in public health facilities of Arba Minch town, Gamo Gofa Zone, Southern Ethiopia. Ethiop J Heal Dev. 2018;32:88–96. doi: 10.1186/s12887-022-03693-5. [DOI] [Google Scholar]
- 18.Wudineh F, Damtew B. Mother-to-Child Transmission of HIV Infection and Its Determinants among Exposed Infants on Care and Follow-Up in Dire Dawa City, Eastern Ethiopia. AIDS Res Treat. 2016;2016:3262746. doi: 10.1155/2016/3262746. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Getaneh Y, Ning F, He Q, et al. Survival and Predictors of Mortality among Adults Initiating Highly Active Antiretroviral Therapy in Ethiopia: A Retrospective Cohort Study (2007-2019) Biomed Res Int. 2022;2022:5884845. doi: 10.1155/2022/5884845. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Arage G, Assefa M, Worku T, et al. Survival rate of HIV-infected children after initiation of the antiretroviral therapy and its predictors in Ethiopia: A facility-based retrospective cohort. SAGE Open Med. 2019;7:2050312119838957. doi: 10.1177/2050312119838957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Bacha T, Tilahun B, Worku A. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy. BMC Infect Dis. 2012;12:197. doi: 10.1186/1471-2334-12-197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Manosuthi W, Charoenpong L, Santiwarangkana C. A retrospective study of survival and risk factors for mortality among people living with HIV who received antiretroviral treatment in a resource-limited setting. AIDS Res Ther. 2021;18:71. doi: 10.1186/s12981-021-00397-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Chi BH, Stringer JSA, Moodley D. Antiretroviral drug regimens to prevent mother-to-child transmission of HIV: a review of scientific, program, and policy advances for sub-Saharan Africa. Curr HIV/AIDS Rep . 2013;10:124–33. doi: 10.1007/s11904-013-0154-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Manasa J, Lessells RJ, Skingsley A, et al. High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa. PLoS ONE. 2013;8:e72152. doi: 10.1371/journal.pone.0072152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Kassa GM. Mother-to-child transmission of HIV infection and its associated factors in Ethiopia: a systematic review and meta-analysis. BMC Infect Dis. 2018;18:216. doi: 10.1186/s12879-018-3126-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Ejigu Y, Tadesse B. HIV testing during pregnancy for prevention of mother-to-child transmission of HIV in Ethiopia. PLoS ONE. 2018;13:e0201886. doi: 10.1371/journal.pone.0201886. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Gupta-Wright A, Fielding K, van Oosterhout JJ, et al. Virological failure, HIV-1 drug resistance, and early mortality in adults admitted to hospital in Malawi: an observational cohort study. Lancet HIV. 2020;7:e620–8. doi: 10.1016/S2352-3018(20)30172-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Liao L, Xing H, Su B, et al. Impact of HIV drug resistance on virologic and immunologic failure and mortality in a cohort of patients on antiretroviral therapy in China. AIDS. 2013;27:1815–24. doi: 10.1097/QAD.0b013e3283611931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Martinez-Picado J, Martínez MA. HIV-1 reverse transcriptase inhibitor resistance mutations and fitness: a view from the clinic and ex vivo. Virus Res. 2008;134:104–23. doi: 10.1016/j.virusres.2007.12.021. [DOI] [PubMed] [Google Scholar]
- 30.Mulugeta A, Henok A, Tewelde T, et al. Determinants of survival among HIV positive research article open access children on antiretroviral therapy in public hospitals, Addis Ababa, Ethiopia. Qual Prim Care. 2017;25:235–41. doi: 10.1186/s40545-022-00448-6. [DOI] [Google Scholar]
- 31.Bhatta L, Klouman E, Deuba K, et al. Survival on antiretroviral treatment among adult HIV-infected patients in Nepal: a retrospective cohort study in Far-western region, 2006-2011. BMC Infect Dis. 2013;13:604. doi: 10.1186/1471-2334-13-604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Tw A. Determinants of Survival among Adults on Antiretroviral Therapy in Adama Hospital Medical College, Oromia Regional state, Ethiopia. J HIV AIDS . 2016;2:1. doi: 10.16966/2380-5536.117. [DOI] [Google Scholar]
- 33.Abebe N, Alemu K, Asfaw T, et al. Survival status of hiv positive adults on antiretroviral treatment in Debre Markos Referral Hospital, Northwest Ethiopia: retrospective cohort study. Pan Afr Med J. 2014;17:88. doi: 10.11604/pamj.2014.17.88.3262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Isaakidis P, Raguenaud M-E, Te V, et al. High survival and treatment success sustained after two and three years of first-line ART for children in Cambodia. J Int AIDS Soc. 2010;13:1–10. doi: 10.1186/1758-2652-13-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Bacha T, Tilahun B, Worku A. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy. BMC Infect Dis. 2012;12:1–8. doi: 10.1186/1471-2334-12-197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Getaneh Y, Zealyas K, Adugna F, et al. HIV drug resistance early warning indicators in Ethiopia: Variability at regional and health facility levels and trend over time. Int J Infect Dis. 2020;95:90–7. doi: 10.1016/j.ijid.2020.02.031. [DOI] [PubMed] [Google Scholar]
- 37.Hamers RL, Sigaloff KCE, Kityo C, et al. Emerging HIV-1 drug resistance after roll-out of antiretroviral therapy in sub-Saharan Africa. Curr Opin HIV AIDS. 2013;8:19–26. doi: 10.1097/COH.0b013e32835b7f94. [DOI] [PubMed] [Google Scholar]
- 38.Asio J, Watera C, Namuwenge N, et al. Population-based monitoring of HIV drug resistance early warning indicators in Uganda: A nationally representative survey following revised WHO recommendations. PLoS ONE. 2020;15:e0230451. doi: 10.1371/journal.pone.0230451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Mutenda N, Bukowski A, Nitschke A-M, et al. Assessment of the World Health Organization’s HIV Drug Resistance Early Warning Indicators in Main and Decentralized Outreach Antiretroviral Therapy Sites in Namibia. PLoS One. 2016;11:e0166649. doi: 10.1371/journal.pone.0166649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Koay WLA, Kose-Otieno J, Rakhmanina N. HIV Drug Resistance in Children and Adolescents: Always a Challenge? Curr Epidemiol Rep . 2021;8:97–107. doi: 10.1007/s40471-021-00268-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Deres G, Nigussie ZM, Chanie MG, et al. Survival time and associated factors among adults living with HIV after initiation of haart in south Gondar, northwest Ethiopia: A retrospective cohort. J Multidiscip Healthc. 2014:1–6. doi: 10.1186/1471-2334-13-604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Eticha T, Berhane L. Caregiver-reported adherence to antiretroviral therapy among HIV infected children in Mekelle, Ethiopia. BMC Pediatr. 2014;14:114. doi: 10.1186/1471-2431-14-114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Melo LSW de, Lacerda HR, Campelo E, et al. Survival of AIDS patients and characteristics of those who died over eight years of highly active antiretroviral therapy, at a referral center in northeast Brazil. Braz J Infect Dis . 2008;12:269–77. doi: 10.1590/S1413-86702008000400003. [DOI] [PubMed] [Google Scholar]
- 44.Kebebew K, Wencheko E. Survival analysis of HIV-infected patients under antiretroviral treatment at the armed forces general teaching hospital, Addis Ababa, Ethiopia. Ethiop J Heal Dev. 2012;26:186–92. doi: 10.4314/ejhd.v26i3. [DOI] [Google Scholar]
- 45.Singogo E, Keegan TJ, Diggle PJ, et al. Differences in survival among adults with HIV-associated Kaposi’s sarcoma during routine HIV treatment initiation in Zomba district, Malawi: a retrospective cohort analysis. Int Health. 2017;9:281–7. doi: 10.1093/inthealth/ihx027. [DOI] [PubMed] [Google Scholar]
- 46.Anandaiah A, Dheda K, Keane J, et al. Novel Developments in the Epidemic of Human Immunodeficiency Virus and Tuberculosis Coinfection. Am J Respir Crit Care Med . 2011;183:987–97. doi: 10.1164/rccm.201008-1246CI. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Waters L, Sabin CA. Late HIV presentation: epidemiology, clinical implications and management. Expert Rev Anti Infect Ther. 2011;9:877–89. doi: 10.1586/eri.11.106. [DOI] [PubMed] [Google Scholar]



