Factors associated with unsuppressed HIV viral load among children under 15 years in sub-Saharan africa: a systematic review

Abstract

Background

Viral suppression among children living with HIV remains suboptimal in sub-Saharan Africa. The marked heterogeneity in suppression rates across countries underscores the need for comparative analyses to elucidate context-specific determinants. This systematic review aims to synthesize existing evidence on factors associated with unsuppressed viral loads in paediatric populations.

Methods

A systematic review was conducted to examine viral load suppression among children under 15 years in sub-Saharan Africa. Comprehensive searches were performed across four major databases: PubMed, Google Scholar, Embase, and Web of Science. Eligible studies were published in English between 2010 and 2024, focused exclusively on paediatric populations in Africa, and available in full text. Relevant data were systematically extracted and compiled in a structured Excel database to prevent duplication and facilitate rigorous, methodologically sound analysis.

Results

Of the 161 articles initially identified, 16 met the predefined inclusion criteria for this review. These studies were conducted across multiple sub-Saharan African countries and used various methodological designs. The most frequently reported factors associated with an unsuppressed viral load among children receiving antiretroviral therapy (ART) were suboptimal treatment adherence, malnutrition, low maternal educational attainment, a high baseline viral load, and missed clinical appointments. Adherence to ART was the most extensively analysed variable, and poor adherence was consistently and strongly associated with virological failure.

Conclusion

Viral suppression among children living with HIV in sub-Saharan Africa remains unacceptably low. This review emphasized key preventable factors mostly poor adherence. Targeted, urgent interventions are needed to improve outcomes for this vulnerable population.

Context

Paediatric HIV remains a major public health challenge in sub-Saharan Africa, which bears approximately 80% of the global burden of children living with HIV [1]. Despite international efforts, including the UNAIDS 95-95-95 targets, viral load suppression among children is significantly lower than among adults [2, 3]. As of 2024, an estimated 84% of children living with HIV in sub-Saharan Africa had achieved viral suppression compared to 94% of adults [1].

An estimated 1.8 million children under the age of 15 were living with HIV in sub-Saharan Africa in 2022. Despite this substantial disease burden, the implementation of the prevention of mother-to-child transmission (PMTCT) remains insufficient. For example, the Democratic Republic of the Congo (DRC) reported an MTCT rate of 25% in 2023, indicating persistent gaps in PMTCT coverage [1]. Furthermore, early infant diagnosis is suboptimal throughout the region, with only 64% of HIV-exposed infants undergoing timely virological testing [4]. These shortcomings underscore critical barriers to achieving effective paediatric HIV control and highlight the need for strengthened maternal and child health interventions.

Access to antiretroviral therapy (ART) remains critically inadequate among children living with HIV in Africa, with only 57% of HIV-positive children receiving treatment in 2024 compared to 76% of adults [5]. Achieving viral load suppression, an essential marker of therapeutic efficacy, continues to be a major challenge due to suboptimal adherence and limited access to routine virological monitoring [6]. To address these persistent issues, global initiatives like the Global Alliance to End AIDS in Children by 2030 and the introduction of child-friendly antiretroviral formulations, such as dolutegravir in syrup form, have been launched to enhance access to treatment, adherence, and outcomes in paediatric populations [5].

Failing to suppress the viral load of children living with HIV significantly increases their risk of adverse clinical outcomes, including higher susceptibility to opportunistic infections and accelerated progression to AIDS-related morbidity and mortality [7]. Furthermore, sustained viral replication promotes the development of drug-resistant HIV strains, which limits future therapeutic options. At the population level, the proliferation of resistant variants reduces the effectiveness of initial antiretroviral regimens and increases the risk of transmission, which hinders progress toward controlling the epidemic and threatens the long-term success of global HIV response strategies [8].

Disparities in viral suppression rates among children living with HIV persist across sub-Saharan Africa. South Africa, for example, has demonstrated comparatively higher rates of viral suppression, reflecting its robust paediatric HIV care infrastructure. In contrast, countries including Benin, Ethiopia, Senegal, and Uganda continue to report viral load rates exceeding 50%, indicating substantial gaps in treatment coverage, adherence support, and virological monitoring [2, 9, 10]. Numerous studies have investigated the determinants of viral load suppression among children in sub-Saharan Africa, revealing converging and divergent findings. These findings include inconsistencies among studies conducted within the same national context [11, 12, 13]. These variations can be attributed to contextual differences between and within countries, such as disparities in healthcare infrastructure, program implementation, sociocultural dynamics, and regional policy frameworks [2, 14].

In an era of increased regional mobility, understanding shared and context-specific barriers is critical. A systematic review that synthesizes and compares findings across diverse national contexts is a valuable opportunity to identify cross-cutting determinants that can be addressed through broad-based interventions, as well as country-specific factors that require tailored, context-sensitive strategies. The goal of this review is to bridge the knowledge gap by identifying the most important factors associated with an unsuppressed viral load in children with HIV in sub-Saharan Africa. Ultimately, this will inform more effective, integrated, and scalable pediatric HIV care strategies across the region.

Methodology

Search strategy

A comprehensive literature search was conducted using four electronic databases—PubMed, Google Scholar, Embase, and Web of Science—to identify studies reporting on viral load suppression and associated factors among children under 15 years of age with unsuppressed viral load. The search strategy used a combination of relevant keywords, including “suppression,” “unsuppressed,” “viral load,” “child,” and “HIV.” In addition to the electronic search, a manual search was performed on the official websites of key international organizations, such as the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS), to identify gray literature and relevant institutional reports. The titles and abstracts of the retrieved records were screened for relevance, and the full texts of the articles were obtained for a more thorough review. Reference lists of included studies were examined to identify additional relevant literature. The snowball sampling technique was also used to expand the pool of eligible studies.

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Eligibility criteria

After conducting an initial literature search, we applied predefined inclusion and exclusion criteria to refine the selection of studies. To be eligible for inclusion, articles had to be published in English, focus exclusively on children under 15 years of age, and explicitly report HIV viral load suppression status (either suppressed or unsuppressed). Eligible studies addressed factors associated with viral suppression or the lack thereof or described interventions aimed at improving suppression outcomes.

Articles were excluded if they fell outside the African context, targeted other population groups (such as adolescents, young adults, adults, or pregnant women), combined pediatric populations under 15 years of age with older cohorts without disaggregated data, or were published in languages other than English. Studies for which full-text versions were unavailable were also excluded. Additionally, only guidelines and reports presenting original data with clearly described methodologies for outcome assessment were included in the review.

Data collection and extraction

All literature identified through the search strategy was systematically cataloged in an Excel database. The database recorded the year of publication, author(s), and article title. This facilitated the identification and removal of duplicates and ensured comprehensive tracking of all retrieved sources. Each article underwent a multi-stage screening process. First, the title was reviewed. Then, the abstract was screened based on the predefined inclusion and exclusion criteria. Articles meeting these criteria were then evaluated based on the full text. Those deemed eligible for inclusion were flagged and incorporated into the final review dataset.

Results and discussion

The first 100 titles in each of the searched databases were screened using the publication year filter from 2010 to 2024. A total of 161 articles were initially identified. After a full-text review and application of the predefined exclusion criteria, 144 articles were excluded. Sixteen studies ultimately met the eligibility criteria and were included in the final review, comprising thirteen articles retrieved from PubMed and three from Google Scholar.

Of the 16 studies included in this review, 14 used primary data sources and two used secondary data analyses. In terms of study design, nine employed cross-sectional methodologies, four were cohort studies, two adopted a case-control design, and one was a randomized controlled trial (Table 1). Data collection relied primarily on patient medical records, institutional databases, and structured questionnaires. Binary and multivariate logistic regression models were the most frequently used statistical approaches for identifying factors associated with unsuppressed HIV viral load in pediatric populations.

Table 1.

Summary of included studies

Reference ID	Country	Study Design	Publication Year	Sample size
2	Ivory Coast	Retrospective, descriptive and analytical	2021	329
9	Ethiopia	Cross-sectional	2023	522
8	Ethiopia	Case‒control	2021	370
10	Uganda	Retrospective cohort	2021	300
18	Kenya	Case‒control	2018	1190
20	Ghana	Cross-sectional	2021	250
15	Tanzania	Cross-sectional	2023	253
27	Mozambique	Cross-sectional	2019	33,559
28	Ethiopia	cluster randomized trial	2023	82
16	Ethiopia	Cross-sectional	2019	1567
17	Nigeria	Cross-sectional	2023	2490
19	Kenya	Retrospective cohort	2019	7667
23	Eswatini	Cross-sectional	2019	377
30	South Africa	Cross-sectional	2013	279
21	South Africa	Retrospective cohort	2015	152
24	South Africa	Cross sectional	2017	322

Regarding gender distribution, only three studies reported a predominantly female paediatric population. In contrast, 56% of the included studies had a male majority among the participants. Additionally, more than half of the studies involved cohorts in which most children were over 5 years old at the start of antiretroviral therapy (ART). Notably, four studies reported that at least 50% of the mothers of HIV-positive children receiving ART were illiterate. This highlights a potential sociodemographic barrier to effective pediatric HIV management. .

Factors associated with unsuppressed HIV viral load in children were categorized into multiple thematic domains, including: adherence to antiretroviral therapy (ART), nutritional status, maternal educational level, CD4 + cell count, disclosure of HIV status, baseline viral load, World Health Organization (WHO) clinical stage 4 at ART initiation, history of ART regimen substitution, prior antituberculosis treatment, missed clinical appointments, sex, ART-related adverse effects, and age at treatment initiation (Table 2)

Table 2.

List of factors

Factors	Number of studies Reporting an Association	Number of studies Reporting No Association	Number of studies Not Assessing the Factor	Comments
Adherence to ART	7	2	8	The definition of adherence varied across studies and included self-reporting, pill counting, and electronic monitoring, each with different classification thresholds. .
Nutritional status	4	1	11	The assessment methods used ranged from general clinical classifications to anthropometric indices, such as Z-scores. Several studies did not specify the method used. .
Maternal level of education	3	1	12
CD4 + cell count	2	1	13
Baseline viral load	4	1	11
Disclosure of HIV status	4	0	12
History of ART regimen substitution	3	1	12	The definition of ART regimen substitution history varied across the included studies. Some studies classified substitution based solely on regimen type (e.g., first- versus second-line therapy), while others incorporated additional parameters, such as the reasons underlying treatment modification and the cumulative history of regimen changes. .
History of tuberculosis treatment	4	2	10
Sex	3	4	9
ART-related side effects	2	0	14
Age at ART initiation	3	3	10

Adherence to ART

Among children living with HIV, adherence to antiretroviral therapy (ART) was the most consistently examined determinant of viral load suppression. Seven studies identified a statistically significant association between suboptimal adherence and unsuppressed viral load. Two studies, however, reported no such association [2, 8, 9, 10, 15]. Together, these results highlight the importance of adherence in achieving virological suppression. Maintaining therapeutic plasma drug concentrations that effectively inhibit HIV replication requires optimal adherence to ART, thereby reducing viral load over time [17]. Conversely, poor adherence allows for sustained viral replication, accelerates the development of drug resistance, and increases susceptibility to opportunistic infections. This ultimately leads to virological failure and clinical deterioration [15].

In contrast, a study conducted in Ethiopia found that some children who adhered well to antiretroviral therapy still had persistently high viral loads [16]. This paradoxical finding may be due to several factors, including drug-resistant HIV variants, rapid metabolism, impaired gastrointestinal absorption, and the persistence of viral reservoirs in immune-privileged sites, all of which can result in subtherapeutic drug concentrations. In younger children, virological failure despite adequate adherence may also be influenced by an immature immune system or errors in drug preparation and administration that can compromise therapeutic efficacy [16].

Nutritional status

Of the five studies assessing the relationship between nutritional status and virological outcomes, four reported a significant association between malnutrition and unsuppressed viral load in children with HIV [2, 8, 15, 17].,. Nutritional status plays a critical role in modulating the effectiveness of antiretroviral therapy (ART) and achieving viral suppression. Adequate and balanced nutrition has been shown to mitigate ART-related adverse effects, thereby enhancing adherence and therapeutic continuity. Furthermore, sufficient nutritional intake supports immune system recovery following the initiation of ART, thereby facilitating more effective viral suppression. Specific nutrients may also contribute to regulating chronic HIV-associated inflammation, which could enhance the immunologic and virologic response to treatment [17]. Malnutrition, including severe acute malnutrition and micronutrient deficiencies, has been associated with diminished and delayed virologic responses to antiretroviral therapy, contributing to suboptimal viral suppression. Inadequate nutrition compromises immune function, which facilitates increased HIV replication and exacerbates susceptibility to opportunistic infections. This immunologic impairment further undermines the effectiveness of ART, delaying immune recovery and perpetuating virologic failure [2].

On the other hand, a study conducted in Kenya did not identify a statistically significant association between nutritional status and viral load suppression [18]. The absence of an association could be due to differences in study populations, methods, or contextual factors, such as the quality of clinical care and the effectiveness of nutritional monitoring systems. It is important to note that malnutrition was assessed using different indicators in each study, including clinical evaluations and anthropometric measurements. This variability in assessment methods may have contributed to the variability in findings.

Maternal education level

Four studies investigated the association between maternal educational level and unsuppressed viral load in children living with HIV [2, 14, 19, 20]. Three of these studies reported a statistically significant association, indicating that children of mothers with no formal education were at an increased risk for virological non-suppression. Limited maternal education may hinder the understanding of HIV disease progression and the critical importance of adhering strictly to antiretroviral therapy [2]. However, a study conducted in Ghana found no significant association, suggesting contextual factors, such as access to structured counseling, targeted health literacy interventions, and strong social support networks, may mitigate the negative effects of low education in certain settings [14]. Maternal education level may indirectly influence pediatric treatment outcomes by shaping caregiving behaviors, medication management practices, and engagement with healthcare services. However, higher levels of literacy may pose challenges to adherence in certain contexts. Increased access to unregulated or misleading online content may cause caregivers to question medical guidance, thereby negatively affecting adherence. These findings underscore the multifaceted and context-dependent role of maternal education in influencing pediatric HIV treatment outcomes.

CD4 and baseline viral load

Several studies examined the predictive value of baseline immunological and virological parameters, specifically CD4 cell count and initial viral load, in relation to virological outcomes. Four studies reported that children with low baseline CD4 counts or high initial viral loads (≥ 1,000 copies/mL) were significantly more likely to experience virological failure. These results highlight the importance of early immuno-virological profiling in identifying pediatric patients at increased risk for an unsuppressed viral load and treatment failure [8, 10, 15, 21]. One study did not observe a statistically significant association between baseline immuno-virological markers and an unsuppressed viral load. However, an elevated initial viral load and reduced CD4 cell counts generally indicate advanced disease progression and diminished treatment efficacy. These findings highlight the importance of baseline virological and immunological parameters, such as high viral load (> 1,000 copies/mL) and low CD4 count, as predictors of virological non-suppression in pediatric patients starting antiretroviral therapy (ART). Previous studies have consistently shown that these markers reflect severe immunosuppression and increased viral replication. Both of these factors complicate the response to ART and increase the likelihood of therapeutic failure [22, 23]. These observations reinforce the critical importance of early HIV diagnosis and the timely initiation of ART to prevent deterioration of immunological and virological status. However, the absence of consistent associations in some studies suggests that additional factors, such as host genetics, viral subtypes, and pharmacokinetic variability, may also independently modulate ART effectiveness [20].

Disclosure of HIV status

Four studies examined the relationship between disclosing HIV status and suppressing viral load in pediatric populations [8, 12, 24, 25]. One study conducted in Ethiopia found that children whose HIV status had not been disclosed to their parents were more than four times as likely to experience virological failure. Other studies observed a positive association between disclosure and viral suppression, but these findings did not reach statistical significance. Disclosure of HIV status may improve adherence by fostering the child’s understanding of their condition and promoting greater engagement and support from caregivers [12]. Although not universally identified as a definitive predictor of virological outcomes, appropriately timed, context-sensitive disclosure appears to facilitate adherence and improve treatment success in children living with HIV.

Studies have shown that not disclosing HIV status can negatively impact a child’s adherence to antiretroviral therapy (ART) [24]. Disclosure improves a child’s understanding of the illness and the rationale for treatment, especially between the ages of six and nine when cognitive development allows for an emerging comprehension of chronic disease. At this stage, children who are informed are more likely to recognize the necessity of ART and adhere to prescribed regimens. Furthermore, disclosing a child’s HIV status to their immediate caregivers can facilitate emotional support, encouragement, and active family involvement. These factors contribute positively to adherence and treatment success [12]. In contrast, nondisclosure may result in confusion, noncompliance, and long-term challenges in treatment engagement and disease management. These findings underscore the critical need for contextually appropriate and culturally sensitive disclosure strategies that are tailored to the child’s age, developmental maturity, and sociocultural environment [25]. These strategies should be incorporated into comprehensive care models that include psychosocial support and caregiver education to reduce stigma, improve communication, and promote sustained viral suppression [12, 21] [24, 24].

The history of ART regimen substitution and the history of tuberculosis treatment

Six studies examined the relationship between antiretroviral therapy (ART) regimen changes and/or a history of tuberculosis (TB) treatment and the likelihood of an unsuppressed viral load [9, 11, 18, 21, 26]. The findings consistently indicated that children with a history of multiple ART regimen substitutions or prior TB treatment were at significantly higher risk for virological non-suppression. Frequent ART regimen changes often indicate underlying treatment failure, suboptimal adherence, or drug intolerance. Similarly, co-treatment with anti-tuberculosis medications can compromise ART efficacy through pharmacokinetic interactions and an increased pill burden, which may negatively affect adherence. These results underscore the importance of vigilant clinical monitoring during regimen transitions and in managing HIV/TB co-infection, emphasizing minimizing treatment interruptions and optimizing therapeutic efficacy.

A history of tuberculosis (TB) has been associated with several factors that may negatively impact virological outcomes in children with HIV. These factors include pharmacological interactions between anti-TB medications and antiretroviral therapies (ART), sustained systemic inflammation, and increased barriers to adherence [30]. Standard TB treatment regimens typically include rifampicin, isoniazid, pyrazinamide, and ethambutol. Rifampicin, a potent inducer of cytochrome P450 enzymes, has been particularly implicated in reduced ART efficacy and virological non-suppression due to its capacity to accelerate the metabolism of key antiretroviral agents (24,31). Furthermore, the concurrent administration of ART and anti-TB therapy substantially increases the overall therapeutic burden, which can compromise adherence and lead to missed doses or interruptions in ART. These challenges underscore the necessity of integrated treatment strategies and intensified adherence support for children undergoing co-treatment for HIV and TB.

Sex

The association between sex and unsuppressed viral load in children receiving antiretroviral therapy (ART) has produced inconsistent results in different studies. While some studies reported higher rates of virological non-suppression among boys, others found higher rates among girls or no significant differences [2, 15, 18, 19, 27, 28, 29, 30]. These divergent results suggest that sex is unlikely to be considered as an independent predictor of virological failure. Instead, sex may function as a confounding or interacting variable influenced by broader contextual factors, such as differential caregiving practices, sociocultural norms, stigma, and sex-specific adherence behaviors, particularly during adolescence. The observed heterogeneity in the findings highlights the necessity of analytical models that consider potential sex-based confounding and interaction effects. These models are needed to more accurately elucidate the pathways through which sex-related factors may indirectly affect treatment outcomes.

ART-related side effects

Two studies investigated the association between adverse effects of antiretroviral therapy (ART) and an unsuppressed viral load in pediatric populations. One study, conducted in Uganda, found that children who reported experiencing ART-related side effects were more than three times as likely to have detectable viral loads [10, 30]. Adverse effects may negatively impact adherence by discouraging consistent medication intake, especially when symptoms are distressing or interfere with daily activities [10]. These findings highlight the importance of routinely monitoring and effectively managing ART-related side effects. This monitoring is an integral part of supporting adherence and achieving virological suppression in children living with HIV.

Age at initiation of treatment

The association between age at antiretroviral therapy (ART) initiation and unsuppressed viral load showed inconsistent results in different studies [15, 27, 28, 30]. While some studies identified a significant association between older age at treatment initiation and an increased risk of virological non-suppression, others reported no statistically significant association. Delayed ART initiation may indicate late HIV diagnosis or more advanced disease at treatment onset. However, age alone is unlikely to function as an independent factor. Rather, its influence is likely modulated by contextual, clinical, and behavioral factors, such as adherence dynamics, caregiver involvement, and access to timely healthcare [15]. Therefore, the effect of age at ART initiation should be interpreted within a broader, multifactorial framework.

Strengths and limitations

This systematic review provides a rare, cross-country perspective on the ongoing challenge of unsuppressed viral loads among children with HIV in sub-Saharan Africa. Through rigorous methodology and a regional focus, the review identifies the most consistent and modifiable drivers of this challenge: poor adherence, malnutrition, and maternal education. This review used a robust multi-database search strategy (PubMed, Google Scholar, Embase, Web of Science), supplemented by manual searches of WHO and UNAIDS sources. Strict inclusion criteria and systematic screening ensured high methodological integrity. By integrating biological, behavioral, and structural factors, the findings provide policymakers and practitioners with the evidence necessary to refine interventions and bridge the pediatric treatment gap. Nonetheless, this review has several limitations that warrant consideration. First, the small number of included studies may limit the generalizability of the findings to diverse settings in sub-Saharan Africa. Second, methodological heterogeneity, particularly in the definitions of key variables such as adherence and nutritional status, as well as in outcome measurement, limits the comparability of results across studies. Third, only including English-language publications introduces the potential for selection bias by excluding relevant studies published in other commonly spoken regional languages, such as French or Portuguese. Fourth, this review is based solely on published data; therefore, the absence of access to primary datasets may have limited the depth of the analysis. Finally, publication bias cannot be ruled out given the increased likelihood of retrieving and publishing studies that report statistically significant findings.

Conclusion

This systematic review revealed that an unsuppressed viral load in children living with HIV in Africa is influenced by maternal, nutritional, treatment-related, and clinical factors. These findings underscore the need for a comprehensive, patient-centered approach integrating antiretroviral therapy, psychosocial support, nutritional care, and comorbidity management to improve viral suppression outcomes in this vulnerable population.

Author contributions

Jacques KANKU conceived the study and supervised the systematic review.Jacques KANKU and Paulin Mutombo conducted the literature search and data extraction.Jacques KANKU, Paulin Mutombo and Aimée Lulebo performed the data analysis.All authors contributed to the writing of the manuscript, reviewed the final version, and approved it for submission.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable. This study is a systematic review of previously published literature, so it did not involve recruiting human participants or collecting primary data.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.