STRENGTHS AND LIMITATIONS OF THIS STUDY

This study attempts to determine the rate of undetectable viral load in children and adolescents starting antiretroviral therapy for the first time in Ethiopia.

This study was conducted in multiple health institutions, encompassing a long-term follow-up period.

Incomplete or missing data due to its retrospective nature may influence the outcomes.

An 8-year study duration might not encompass the latest developments in HIV treatment guidelines or interventions that could affect the results.

This study did not investigate certain possible factors such as monthly income, substance use and family size, which might impact reaching an undetectable viral load.

Background

In 2019, globally, 1.7 million children were affected by HIV.1 In Ethiopia, in the same year, 44 229 children were HIV-positive, and 2055 children died due to AIDS.2

Significant advancements have been achieved in expanding access to antiretroviral therapy (ART) in low-income and middle-income countries. Presently, around the world, approximately 21.7 million individuals are receiving ART, with 15 million of them located in sub-Saharan Africa.3 4 For HIV treatment to be effective in restoring immune functionality, ART should suppress plasma HIV RNA to undetectable states or levels (<50 copies/mL) and improve the quality of life.5 Hence, regular viral load testing is widely recognised as the most effective method for monitoring ART in individuals living with HIV.6 7

Although being virally suppressed and undetectable is the aim of HIV treatment, there are some reasons why a person may not be able to achieve an undetectable viral load. These can include factors outside of someone’s control, including, drug interactions, side effects, adherence challenges and other clinical-related characteristics.8 9

The United Nations Programme on HIV/AIDS (UNAIDS) has set global targets called the 95-95-95 targets to eliminate AIDS as a public health threat by 2030. The third target aims to achieve viral load suppression in at least 95% of individuals living with HIV and receiving ART.10 However, numerous developing countries, including Ethiopia, have not yet achieved these targets. It is essential to compare viral rebound and viral suppression rates based on different clinical attributes, and identifying factors that contribute to increased viral load is crucial for adjusting programme-level strategies. These interventions play a vital role in achieving the global target goals set by UNAIDS and addressing the challenges faced by developing countries in attaining the desired levels of viral suppression.

The viral load testing is a powerful tool, recommended by the WHO for improving the long-term success of ART for HIV. However, less than 20% of ART patients in Africa receive regular viral load monitoring.11

Although various studies have examined survival rates, ART adherence and other aspects among children and adolescents living with HIV, the factors associated with achieving an undetectable viral load have not yet been investigated in Ethiopia, particularly in the study area. Hence, this study aims to examine the viral load undetectable state estimation and its predictors among children and adolescents living with HIV at South Gondar health institutions, Northwest, Ethiopia, 2023.

Methods and materialsStudy setting

The South Gondar health institutions are located in the South Gondar zone, which is located in the Amhara region in the northwest part of Ethiopia. Besides, Debre Tabor town is the capital city of the south Gondar zone, which is 103 km from Bahir Dar (the capital city of the Amhara region) and 665 km from Addis Ababa.

There are nine hospitals and eight health centres that provide ART in the south Gondar zone. ART case team has been in the hospitals including physicians, nurses, pharmacists and laboratory technicians who took comprehensive ART training. ART case team tries to improve the quality of life among children and adolescents living with HIV including voluntary testing and counselling, psychological support and prevention of HIV transmission from mother to child. All children and adolescents who have been followed up in the health institutions have had viral load monitoring annually since 2008 E.C.

Study design and study participants

A retrospective follow-up study was conducted from 1 June 2016 to 30 April 2023, at South Gondar Health Institutions, in 2023. The study included a total of eight hospitals and seven health centres that provide ART services in the South Gondar zone. Four health centres, namely Worta Health Center, Nefas Mewucha Health Center, Mekane Eyesus Health Center and Addis Zemen Health Center, were selected randomly for the study. Additionally, five hospitals, including Debre Tabor Compressive Specialized Hospital, Nefas Mewucha Primary Hospital, Mekane Eyesus Primary Hospital and Addis Zemen Primary Hospital, were also randomly selected as part of the study.

The sample size was estimated using the formula: n=(za/2)2×p(1−p)/d2 where p was assumed to be 50% due to the absence of prior studies. n=(1.96)2×0.5 (0.5)/0.052=384. After accounting for a 10% increase to address potential non-responses or incomplete data, the final sample size was adjusted to approximately 430.

In the ART clinics of the selected hospitals, all children and adolescents living with HIV who initiated ART were identified. The investigator assigned registration numbers to these individuals in chronological order, based on their ART start dates between 1 June 2016 and 30 April 2023. After a thorough review of medical charts and the ART registration logbook, the investigator selected a total of 430 samples that met the predetermined inclusion criteria.

Patient and public involvement

There was no direct public or patient involvement in the design and implementation of this study.

Data sources/measurement

A standard checklist containing study variables has been developed from the children and adolescents registry card which was developed by the Ethiopian Federal Ministry of Health.12 Data were collected from children and adolescents ART record cards and registers from 1 June 2016 to 30 April 2023. The data were collected in terms of patient sociodemographic characteristics, clinical information and treatment-related information. In the data cleaning process, missing variables were recollected and confirmed using paper-based patient ART records and registers. WHO Anthro-Plus software was used to assess the nutritional status of the children and adolescents. The data were collected by nine BSc health professionals and two MSc degrees for supervision who had taken comprehensive HIV care training. Data cleaning and double data entry were carried out to check for any inconsistencies. The quality of the data was assured by giving 2 days of training for data collectors and supervisors. A pretest was conducted on 10% of the sample size.

VariablesViral load undetectable state (event)

An undetectable viral load is where ART has reduced your HIV to such small quantities that it can no longer be detected by standard blood tests usually <50 copies/ML.8 9

Censored

Children and adolescents were classified as censored in the study if they were lost to follow-up or transferred to another healthcare facility before achieving the event of interest (ie, reaching an undetectable viral load state). Additionally, children and adolescents who remained alive until the end of the study period, which was 30 April 2023, were also considered censored.

CD4 count below the threshold for severe immunodeficiency was classified according to age (for infants CD4<1500/mm3, 12–35 months <750/mm3, 36–59 months <350/mm3 and ≥5 years <200/mm3).12

Adherence to ART was categorised based on the percentage of drug dosage taken in relation to the total monthly doses of ART drugs. Adherence levels were classified as good if the percentage exceeded 95%, fair if it ranged between 85% and 94%, and poor if it fell below 85%.13

Statistical methods

The data collected was inputted into Epi Data V.4.4.2 software and then exported to Stata V.17 for analysis. Descriptive statistics such as mean, median and SD were used to summarise continuous variables related to the study participant’s characteristics. Categorical data were summarised using percentages, frequency tables and visual representations such as box plots.

The Akaike information criteria and Bayesian information criteria were employed to compare different models and determine the most efficient one for the analysis. The Kaplan-Meier curve was employed to estimate the cumulative probability of reaching an undetectable viral load state, as well as the median survival time. To identify predictors of viral load undetectable state, the Cox proportional hazards model was used. Assumptions of the model, including proportionality assumptions and goodness of fit, were assessed. Both bivariate and multivariable analyses were conducted, and a 95% CI was computed for the HR. Variables that had a p<0.05 in the multivariable analysis were considered statistically significant and associated with viral load undetectable state.

ResultsSociodemographic characteristics of the study participants

The study enrolled a total of 430 children and adolescents living with HIV. Among these participants, 193 (44.9%) were identified as male. About 255 (59.3%) of the study participants resided in urban areas. Within the group of children and adolescents included in the study, 273 (63.5%) fell into the age range of 11–18 years. When considering their functional status, a significant proportion—379 (90.0%)—were classified as being in the working category. Furthermore, it was observed that a majority of the participants—369 (85.8%)—had disclosed their HIV status.

The parental status of the children and adolescents revealed that a substantial portion of parents, 378 (87.9%) were orthodox, 254 (59.1%) were married and 235 (54.7%) were able to read and write (table 1).

Table 1

Sociodemographic characteristics among children and adolescents living with HIV at South Gondar health institutions, Ethiopia, 2023

Clinical and treatment-related characteristics of the study participants

During the course of the study, a considerable proportion of children and adolescents living with HIV displayed certain health indicators. Specifically, 66 participants (15.3%) had a CD4 count below the threshold level, 72 (16.7%) fell under WHO clinical stages III and IV and 79 (18.4%) had a haemoglobin level below 10 g/L. Moreover, 84 participants (19.5%) had a nutritional status below −2 Z score.

Out of the total participants, 146 (34.0%) experienced opportunistic infections, 73 (17%) exhibited fair or poor adherence to ART, 68 (15.8%) had treatment failure and 44 (10.2%) were diagnosed with tuberculosis.

The majority of participants—406 (94.4%)—received both cotrimoxazole preventive therapy (CPT) and isoniazid preventive therapy (IPT). Additionally, 294 children and adolescents (68.4%) were prescribed TDF+3TC+DTG (4i) and ABC+3TC+DTG (4j) as their ART regimen.

Regarding the duration of follow-up, 262 participants (60.8%) had a follow-up period of less than or equal to 6 months, while 267 (62.1%) had been on ART for 60 months or more.

Throughout the follow-up period, 369 participants (85.8%) achieved an undetectable viral load and 391 (90.9%) survived (table 2).

Table 2

Clinical and treatment-related characteristics among children and adolescents living with HIV at South Gondar health institutions, Ethiopia, 2023

The level of viral load of the study participants over time

The level of viral load of the study participants was estimated from 2016 to 2023. Over the follow-up period, the level of viral load in 2016 was estimated to be 1240 copies/mL, while in 2023, it had decreased significantly and was found 103 copies/mL (figure 1).

Figure 1

The box plot of viral load level among children and adolescents living with HIV at South Gondar health institutions, Ethiopia.

Kaplan-Meier curve and median survival time of viral load undetected state

The average duration of follow-up was 8.5 months (95% CI 8.1 to 8.9)±4.4 SD months. This resulted in a total of 9151 observations over the course of the study. By the end of the follow-up period, 369 children and adolescents (85.8%, 95% CI 82.6% to 88.8%) achieved an undetectable viral load. Furthermore, the median survival time for children and adolescents to reach an undetectable viral load was found to be 6 months (figure 2).

Figure 2

Kaplan-Meier curve of viral load undetected state among children and adolescents living with HIV at South Gondar health institutions.19

Bivariable and multivariable analysis of viral load undetectable state

In the Cox proportional hazard model, the bivariable analysis identified factors associated with the development of an undetectable viral load, with a p value of less than 0.25. These factors included age, residence, educational status, disclosure status, CD4 count, level of ART adherence, haemoglobin status, nutritional status, WHO staging, CPT and IPT prophylaxis, treatment failure, opportunistic infections and duration of follow-up in months. These factors were then included in the multivariable analysis.

In the multivariable models, the following factors were found to be associated with achieving an undetectable viral load during the follow-up period: CD4 count above the threshold level, good level of ART adherence, nutritional status ≥−2 Z score and WHO stages I and II. Children without treatment failure were also more likely to achieve an undetectable viral load. Specifically, children and adolescents with a CD4 count above the threshold level had a 2.8 times higher chance of achieving an undetectable viral load compared with those with a CD4 count below the threshold level (adjusted HR, AHR 2.8, 95% CI 1.5, 5.3). Similarly, children and adolescents with a good level of ART adherence were 2.0 times more likely to achieve an undetectable viral load compared with those with fair/poor adherence (AHR 2.0, 95% CI 1.1, 3.9). Children and adolescents with nutritional status ≥−2 Z score had a 2.3 times higher chance of achieving an undetectable viral load compared with those with nutritional status <−2 Z score (AHR 2.3, 95% CI 1.3, 4.0). Furthermore, children and adolescents without treatment failure had a 2.1 times higher chance of achieving an undetectable viral load compared with those with treatment failure (AHR 2.1, 95% CI 1.1, 4.0) (table 3 and figure 3A–D).

Table 3

Bivariable and multivariable analysis of viral load undetectable among children and adolescents living with HIV at South Gondar health institutions, Ethiopia, 2023

Figure 3

(A–D) Kaplan-Meier of viral load undetected state by CD4 count, level of ART adherence, nutritional status and treatment failure among children and adolescents living with HIV at South Gondar health institutions.19 ART, antiretroviral therapy; CD4, cluster of differentiation 4.

Discussion

This study aimed to analyse the undetectable viral load and identify factors among children and adolescents living with HIV at South Gondar health institutions in Northwest Ethiopia. The study revealed that the level of undetectable viral load in South Gondar health institutions was found to be 85.8% (95% CI 82.6% to 88.8%). Over time, there was a significant decrease in viral load levels, with the level of 1240 copies/mL in 2016 and 103 copies/mL in 2023. Additionally, the median survival time for children and adolescents to reach an undetectable viral load was found to be 6 months.

The results of this study indicate that the findings fall below the target set by WHO in their strategic plans to achieve the Sustainable Development Goal of 95-95-95 by 2025.10 The results of this study are highly significant as they offer valuable evidence for designing targeted interventions in healthcare institutions. These interventions aim to align with and support the ambitious plans established by the WHO.

In contrast, the proportion of children and adolescents who achieved an undetectable viral load in this study was higher compared with a study conducted in eight countries, including South Africa, the USA, Thailand, Mali, Burkina Faso, Swaziland and India.14 Additionally, studies conducted in Cameroon, Cambodia and Uganda reported viral undetectable rates of 72.1%, 76.8% and 89%, respectively.15 16 The observed difference in viral load undetectable rates could be attributed to variations in the measurement cut-off point and study design. Most of the aforementioned studies were cross-sectional, whereas our study followed a cohort design. Additionally, differences in the study area, duration of time on ART and varying lengths of follow-up periods might have contributed to the disparities.

The median survival time required to achieve an undetectable viral load in this study was similar to a study conducted in Oromia, Ethiopia, which reported a median survival time of 181 days (95% CI 140.5 to 221.4).13 However, the median survival time observed in our study was longer compared with a study conducted in the Netherlands, where the median survival time to achieve an undetectable viral load was reported as 60 days (12–168 days).17 Furthermore, the median plasma viral load observed in our study was similar to that reported in a study conducted in Kenya, which noted a value of 1.65×103 cells/µL,18 The median plasma viral load in our study, as reported in reference Tesfahunegn et al,19 was lower compared with a study conducted in Uganda, where it was found to be 8.1×104 cells/µL.15 The median plasma viral load in our study, as referenced in Tchouwa et al,16 was lower than a study conducted in Oromia, Ethiopia, where it was reported as 2.03×105 cells/µL.13 The observed difference in viral load levels could be attributed to variations in the monitoring period and study duration. Recently, viral load monitoring has become the gold standard for assessing HIV treatment effectiveness, surpassing CD4 count measurements. In our study, conducted more recently, regular viral load monitoring was implemented, allowing for continuous feedback to healthcare providers and study participants. This approach aims to improve the quality of life for individuals living with HIV.

Our study found that children with good adherence to ART had 2.1 times higher likelihood of achieving an undetectable viral load compared with children and adolescents with fair/poor adherence. This finding is consistent with a study conducted in Uganda.11 This can be attributed to the fact that maintaining a high level of adherence to ART is crucial in preventing viral failure, reducing the risk of viral transmission and decreasing HIV/AIDS-related deaths in order to achieve viral suppression.19 20 Additionally, in our study, children and adolescents with a nutritional status of ≥−2 Z score had 1.8 times higher likelihood of achieving an undetectable viral load compared with children with a nutritional status >−2 Z score. This finding aligns with the results of a study conducted in a different setting.21

This could be attributed to the fact that malnutrition is a significant contributor to childhood morbidity and can weaken the immune system, leading to an increase in viral load levels, both independently and in combination with other illnesses.22 23

In our study, children and adolescents with a CD4 count above the threshold level had 2.0 times higher likelihood of achieving an undetectable viral load compared with children with a CD4 count below the threshold level. This finding is consistent with a study conducted in Uganda.11 This can be explained by the fact that low CD4 cell counts and immune activation are both associated with higher viral load levels and increased risk of non-AIDS-related mortality. These conditions make children more susceptible to opportunistic infections, leading to difficulties in achieving an undetectable viral load.24 25

In our study, children and adolescents who did not experience treatment failure had 3.0 times higher likelihood of achieving an undetectable viral load compared with children who had treatment failure. This finding aligns with the results of studies conducted in Cameroon and Uganda.15 16 This can be attributed to several reasons that can lead to an increase in viral load. These reasons include inconsistent adherence to antiretroviral medication, genetic mutations in the HIV virus and incorrect dosing of antiretroviral medication.26 27

Despite the efforts made in this study to estimate the undetectable viral load among children and adolescents initiating ART in Ethiopia across multiple health institutions with a long-term follow-up period, there are several limitations to consider. First, the retrospective design of the study introduces the possibility of incomplete or missing data due to reliance on existing medical records, potentially impacting the accuracy and comprehensiveness of the analysis. Second, the study’s 8-year duration may not fully capture the most recent advancements in HIV treatment guidelines and interventions that could influence treatment outcomes. As HIV care and management continue to evolve, the findings of this study may not fully reflect the current landscape of HIV treatment practices. Additionally, it is important to acknowledge that certain potential predictors, such as monthly income, substance use and family size, were not thoroughly investigated in this study. These factors have the potential to influence the achievement of an undetectable viral load but were not examined in detail. The absence of these variables limits the comprehensive understanding of the various factors that can impact treatment outcomes among children and adolescents living with HIV.

Conclusion

The lower proportion of individuals achieving an undetectable viral load compared with the target set by the WHO strategic plan (95-95-95 target by 2025) highlights the need for targeted interventions and improved HIV management strategies. Factors such as CD4 count, ART adherence, nutritional status and treatment failure play a significant role in achieving viral load undetectable state. Healthcare providers better prioritise these factors through comprehensive care and support. The study emphasises the importance of aligning efforts with the WHO strategic plan to meet targets and improve treatment outcomes. Therefore, stakeholders better address the identified predictors to enhance care and support for this vulnerable population.

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

Ethics statementsPatient consent for publication

Not applicable.

Ethics approval

Ethical clearance was obtained from the ethics review committee at Debre Tabor University. Additionally, permission letters were obtained from each of the South Gondar health institutions involved in the study. In order to maintain confidentiality, the names and medical identification numbers of the children were not collected.

Acknowledgments

First and foremost, we would like to extend our sincere appreciation to Debre Tabor University for its support. Secondly, we would like to express our heartfelt gratitude to the study participants, the ART focal person, the staff of each health institution and the dedicated data collectors who made this study possible.