Abstract
Background
Left ventricular systolic dysfunction (LVSD) is an emerging non-communicable complication among children living with Human Immunodeficiency Virus (HIV), particularly in Sub-Saharan Africa, where paediatric HIV burden remains high. However, reported prevalence varies widely across studies and treatment eras, reflecting differences in antiretroviral therapy (ART) exposure, disease severity, and diagnostic criteria.
Aim
To estimate the prevalence of LVSD among children living with HIV in Sub-Saharan Africa and evaluate study-level factors associated with variability.
Methods
A systematic review was conducted according to PRISMA 2020 guidelines. Databases including PubMed, MEDLINE, Scopus, AJOL, and ScienceDirect were searched. Studies reporting echocardiographically defined LVSD (EF < 55% or FS < 28%) in individuals aged 0–19 years were included. Random-effects meta-analysis was performed using RevMan 5.4. Subgroup analyses were conducted by ART era, ART coverage, echocardiographic method, ART duration, and study quality. Sub-group and meta-regression analyses were performed using R (metafor package). Publication bias was assessed using Egger’s test.
Results
Twenty studies (n = 3,994) were included. The pooled prevalence of LVSD was 6.0% (95% CI: 3.0–12.0%) with high heterogeneity (I² = 95%). Prevalence was substantially higher in pre-ART/early ART studies (27.8%) compared with ART-era studies (3.6%). Studies with ≥ 80% ART coverage reported lower prevalence (2.6%) compared with < 80% coverage (12.8%). There was, however, persistent high heterogeneity in subgroup analyses. Meta-regression showed that increasing ART coverage was associated with lower LVSD prevalence (OR 0.75 per 10% increase; p = 0.01). Echocardiographic method significantly influenced estimates, with FS-based studies reporting higher prevalence than EF-based studies. Egger’s test showed no evidence of publication bias (p = 0.86).
Conclusion
LVSD remains present in a persistent proportion of children living with HIV in Sub-Saharan Africa, although prevalence varies substantially across settings and treatment eras. Higher ART coverage and sustained treatment are associated with lower prevalence. Findings should be interpreted cautiously due to high heterogeneity. Longitudinal studies using standardised definitions are needed.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1186/s12879-026-13874-7.
Keywords: Paediatric HIV, Left ventricular systolic dysfunction, Sub-Saharan Africa, Echocardiography, ART, Systematic review
Background
The World Health Organization reported in 2023 that 1.4 million children aged 0–14 years were living with HIV [1], and 90% of these children live in Sub-Saharan Africa [2]. In Nigeria, about 21,000 children were infected with HIV in 2020, and 47 children die of HIV/AIDs every day [3]. Children accounted for 10% of all new HIV infections and 18% of all deaths from AIDS-related causes in 2020 [1, 4, 5].
While most of the mortality from HIV/AIDs in children and adolescents is still due to opportunistic infections [6], improved survival rates from more effective ART and wider ART coverage have led to increasing concerns about long-term cardiovascular complications of the disease and how these affect morbidity and mortality from HIV/AIDs [7].
Left ventricular systolic dysfunction (LVSD) is an important cardiovascular complication in children living with HIV, particularly in Sub-Saharan Africa. Previous studies have reported a significant prevalence of cardiac abnormalities in HIV-infected children [8–12]. However, existing reviews have largely focused on adult populations, combined heterogeneous cardiac outcomes, or have not provided region-specific pooled estimates for Sub-Saharan Africa. Furthermore, few studies have specifically synthesised data on LVSD as a distinct outcome.
The mechanisms underlying LVSD in HIV-infected children are multifactorial [8, 13] and can be broadly grouped into:
HIV-related factors: direct myocardial injury, chronic inflammation, immunosuppression.
Treatment-related factors: cardiotoxic effects of specific antiretroviral drugs.
Environmental and host factors: malnutrition, anaemia, and co-morbid infections.
LVSD is clinically important because it may progress to symptomatic heart failure and is associated with increased morbidity and mortality, even when initially subclinical [8, 13]. Children living with HIV in Sub-Saharan Africa may be disproportionately affected due to delayed diagnosis, advanced immunosuppression, lower antiretroviral therapy coverage, co-morbid malnutrition, and limited access to specialized cardiovascular care [8, 12, 13].
Despite the available data on left ventricular systolic dysfunction and its implications on the long-term morbidity of children and adolescents living with HIV, the baseline and follow-up cardiac evaluation, including echocardiography, is still not recommended as routine care for HIV-infected children by the World Health Organisation or local country guidelines [14, 15].
This study aims to estimate the prevalence of LVSD among children living with HIV in Sub-Saharan Africa and to examine study-level factors contributing to variability in reported prevalence.
Methods
Data sources and searches
This review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines and is registered with the International Prospective Register of Systematic Reviews (PROSPERO) (Prospero Registration ID: CRD420251172125). The PRISMA flow diagram is provided in the results section as Fig. 1, and the full PRISMA checklist is provided as an additional file.
Fig. 1.
PRISMA flow diagram [21]
A comprehensive literature search was carried out for articles published between January 1990 and December 2023; this range of dates was chosen to cover all studies across the spectrum of development and evolution of ART. Literature search was done across the following databases – PubMed, MEDLINE, Scopus, African Journals Online (AJOL), and ScienceDirect. The search strategy combined Medical Subject Headings (MeSH) and free-text terms related to HIV, left ventricular systolic dysfunction, and paediatric populations. Boolean operators were used to combine concepts. A typical PubMed search string was: (“HIV” OR “human immunodeficiency virus” OR AIDS) AND (“left ventricular dysfunction” OR “systolic dysfunction” OR “ejection fraction” OR “fractional shortening”) AND (child* OR pediatric* OR paediatric* OR adolescent*) AND (“Sub-Saharan Africa” OR Nigeria OR Kenya OR Uganda OR Ghana OR Tanzania OR Ethiopia).
The search strategy was adapted appropriately for each database. The full database-specific search strategies are provided as Supplementary Material S1. The filters applied were for Language: English only and for Publication date: January 1990 – December 2023. Additional search methods included manual screening of reference lists of included articles to identify further relevant studies.
Study screening and selection
The results were screened for duplicates, which were subsequently removed. This was followed by title and abstract screening, which was done independently by two researchers (KB and IE). Full texts of eligible articles were then accessed for full-text screening. All full-text articles were double-screened, independently, by two members of the research team (KB and IE). Conflicts were resolved by consensus.
This review included studies of HIV-infected children and adolescents (0–19 years), reporting on the prevalence of left ventricular systolic dysfunction (LVSD). For studies that had multiple reports, the study with the larger number of cases or longer duration of follow-up in the case of cohort studies was included. However, relevant, complementary information from multiple reports of the same study was extracted. Exclusion criteria included: studies with sample size < 30, studies including only individuals > 19 years of age, studies reporting exclusively on the prevalence of pericardial diseases or myocarditis, or valvular heart diseases, studies of HIV patients where participants were selected based on suspected or known cardiac disease, reports based on autopsy examination to diagnose heart disease, studies reporting biomarker outcomes only, e.g., elevated brain natriuretic peptide or cardiac troponin, and situations where the study did not provide sufficient data to estimate frequency or relative risk of cardiac dysfunction in individuals with HIV, and studies not published or not available in the English language. The exclusion of studies not available in English is acknowledged as a limitation that may adversely affect the review’s regional representativeness, as French and Portuguese are also common languages in Sub-Saharan Africa. It was, however, necessary, considering the research team’s linguistic literacy was limited to English.
Data extraction
Two investigators (KB and IE) independently extracted data from studies deemed eligible for inclusion in the review. Discrepancies were resolved by consensus. Data was extracted on several study-level variables, including study characteristics (e.g., design, location and period of study); demographics (e.g., average age, proportion of males) and echocardiographic parameters (e.g. ejection fraction [EF]), HIV characteristics (mean CD4 T-cell count, proportion with AIDS, proportion on anti-retroviral treatment, proportion virally suppressed and mean duration of treatment), criteria for defining left ventricular dysfunction and prevalence estimates. The data extracted was summarized and presented in tabular form.
Outcome definition
For meta-analysis, studies with sufficiently similar definitions of left ventricular systolic dysfunction (LVSD) were pooled together to avoid combining studies with disparate outcomes. For LVSD, our definition was ejection fraction (ejection fraction) < 55% or fractional shortening (FS) < 28%, as both are established echocardiographic thresholds of LVSD in paediatric populations. However, because these measures are not entirely interchangeable and may yield different prevalence estimates, the echocardiographic method was prespecified as a potential source of heterogeneity and explored through subgroup analysis and meta-regression. For studies reporting frequency using different EF/FS cut-offs, the data providing the closest definition to our definition of LVSD was selected. Studies using echocardiographic definitions close to the prespecified LVSD threshold were included when they clearly assessed reduced LV systolic function. One included study used a stricter fractional shortening threshold of FS < 25%; this was retained in the primary analysis because it represented a conservative definition of LVSD. Sensitivity analysis excluding this study was performed to assess its influence on the pooled estimate.
Data synthesis
Where available, study characteristics such as average age of participants, proportion of males, proportion on antiretroviral therapy (ART), and others were summarized for discussion. Data that were available in only a few of the studies included were not quantitatively summarized and were provided only as a narrative synthesis.
The major study-specific measure (i.e., prevalence of LVSD) was pooled using random-effects meta-analysis of logit-transformed proportions. This was done to stabilize variances across studies with differing sample sizes and low event rates. Meta-regression analyses were conducted using mixed-effects models with restricted maximum likelihood estimation to account for between-study heterogeneity.
Random-effects prevalence pooling and forest plot generation were initially performed using Review Manager (RevMan 5.4, The Cochrane Collaboration). Meta-regression and advanced subgroup analyses were subsequently conducted in R (R Foundation for Statistical Computing, Vienna, Austria) using the metafor package, as meta-regression is not supported within RevMan.
The methodological quality of the individual studies was assessed using the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional studies [16]. This scale is calculated by assigning points to the following three aspects of study design, with a maximum possible 10 points for cross-sectional studies: selection of study participants (maximum 5 points), comparability (maximum 2 points), and ascertainment of the outcome of interest (maximum 3 points). Studies with scores of 7–9 were classified as having low risk of bias (high-quality), 5–6 as having moderate risk of bias (moderate quality), and 0–4 as having high risk of bias (low-quality).
The assessment of between-study heterogeneity was done using Q and I2 statistics [17–19]. Sources of heterogeneity were explored using subgroup analyses and meta-regression by the following study-level characteristics: ART era (pre/early-ART vs. Modern ART), ART coverage (≥ 80% and < 80%), echocardiographic method (FS vs. EF), and study quality, proportion of participants with AIDS (≥ 50% vs. < 50%). Meta-regression coefficients were estimated on the logit scale and exponentiated to generate odds ratios for moderator effects. Publication or small-study bias was assessed using Egger regression test P value for funnel-plot asymmetry [20]. Statistical tests were two-sided and used a significance level of P < 0.05.
Results
Overview of the search process
Following an exhaustive search of the stipulated databases, a total of 1278 records were found. It was shown in Fig. 1 below that during the process of de-duplication, 201 duplicates were excluded, resulting in 1,077 studies that were screened for title and abstract. Consequently, 860 records during title and abstract screening were excluded, resulting in 217 articles that were assessed for full-text eligibility screening. A total of 20 articles after the full-text screening met the final criteria for the review and were included in the meta-analysis.
Characteristics of the included studies
The 20 included studies were conducted across Sub-Saharan Africa, with most from Southern Africa (40%) and Nigeria (30%). Sample sizes ranged widely, from 47 to 643 participants. Early ART-era studies (2005–2012) [8, 9, 22, 23] reported noticeably higher LVSD prevalence, while modern ART-era studies (2013–2023) [2, 10, 12, 24–36] showed very low rates, often below 3%. Echocardiographic assessment varied, with Nigerian studies largely applying fractional shortening < 28%, while East and Southern African studies applied EF < 55%. Of the studies reporting the proportion of patients on ART, 11 reported that all the included patients were on ART [2, 8, 26, 28–34, 36] while nearly all the patients in the earliest included study by Lubega et al. [9] were ART-naïve. Table 1 illustrates the detailed characteristics of these studies.
Table 1.
Characteristics of the included studies
| Author (Year) | Country (Region) | Study Design | Sample Size (HIV-infected) | Age Range / Mean Age | ART Status (%) | AIDS Proportion (%) | Echocardiographic Criteria for LVSD | LVSD Cases (n) | LVSD Prevalence (%) |
|---|---|---|---|---|---|---|---|---|---|
| Lubega 2005 [9] | Uganda (East Africa) | Cross-sectional | 230 | Children & adolescents | 0.4 | 18.3 | FS < 28% | 39 | 17.0 |
| Brown 2005 [22] | South Africa (Southern Africa) | Cross-sectional | 90 | < 18 years | NS | NS | FS < 25% | 15 | 16.7 |
| Ige 2012 [23] | Nigeria (West Africa) | Cross-sectional | 150 | 3–14 years | 56 | 26 | FS < 28% | 75 | 50.0 |
| Okoromah 2012 [8] | Nigeria (West Africa) | Cross-sectional | 83 | Children | NS | 83.9 | FS < 28% | 28 | 33.7 |
| Miller 2013 [24] | Zimbabwe (Southern Africa) | Cross-sectional | 110 | 6–16 years | 71 | NS | EF < 55% | 6 | 5.5 |
| Chelo 2015 [25] | Cameroon (Central Africa) | Cross-sectional | 100 | 2–18 years | 91 | 33 | FS < 28% | 1 | 1.0 |
| Arodiwe 2016 [12] | Nigeria (West Africa) | Cross-sectional | 90 | Paediatric | NS | 17.7 | FS < 28% | 24 | 26.7 |
| Namuyonga 2016 [26] | Uganda (East Africa) | Cross-sectional | 285 | 5–15 years | 100 | 34 | EF < 55% | 6 | 2.1 |
| Sanyahumbi 2017 [27] | Malawi (Southern Africa) | Cross-sectional | 222 | 4–16 years | 67 | NS | EF < 55% | 6 | 2.7 |
| Majonga 2018 [2] | Zimbabwe (Southern Africa) | Cross-sectional | 197 | Adolescents (10–19) | 100 | NS | EF < 55% | 4 | 2.0 |
| McCrary 2018 [28] | Kenya (East Africa) | Cohort baseline (prevalence used) | 302 | Adolescents | 100 | NS | EF < 55% | 10 | 3.3 |
| Manafe 2019 [29] | Mozambique (Southern Africa) | Cross-sectional | 47 | Children | 100 | 21.3 | EF < 55% | 5 | 10.6 |
| Frigati 2019 [30] | South Africa (Southern Africa) | Cohort baseline | 384 | Adolescents | 100 | 77.9 | EF < 55% | 1 | 0.3 |
| Mahtab 2020 [31] | South Africa (Southern Africa) | Cross-sectional | 474 | 9–14 years | 100 | 78 | EF < 55% | 1 | 0.2 |
| McCrary 2020 [10] | Kenya (East Africa) | Cross-sectional | 643 | 10–24 years | 100 | NS | EF < 55% | 21 | 3.3 |
| Duru 2020 [32] | Nigeria (West Africa) | Cross-sectional | 71 | Paediatric | 100 | 18.3 | FS < 28% | 6 | 8.5 |
| Majonga 2020 [33] | Zimbabwe (Southern Africa) | Cross-sectional | 175 | Adolescents | 100 | NS | EF < 55% | 2 | 1.1 |
| Wubayehu 2020 [34] | Ethiopia (East Africa) | Cross-sectional | 151 | Children & adolescents | 100 | 63.6 | EF < 55% | 3 | 2.0 |
| Arodiwe 2023 [35] | Nigeria (West Africa) | Cross-sectional | 90 | 6–18 years | 71 | 17.8 | FS < 28% | 13 | 14.4 |
| Garba 2023 [36] | Nigeria (West Africa) | Cross-sectional | 100 | Paediatric | 100 | 0 | EF < 55% | 8 | 8.0 |
Risk of bias
Table 2 below provides the risk of bias results of the twenty studies included in this meta-analysis using the Newcastle–Ottawa quality assessment scale modified for cross-sectional studies. 14 of the studies included (70%) were deemed to have a low risk of bias while 6 (30%) were deemed to have a moderate risk of bias. Most of the weaknesses noted were in the selection with many studies failing to account for non-response participants and not providing adequate justification for their sample size.
Table 2.
Risk of bias results
| Study (Year) | Selection (0–5) | Comparability (0–2) | Outcome (0–3) | Total NOS Score | Quality Rating |
|---|---|---|---|---|---|
| Lubega 2005 | 3 | 2 | 3 | 8 | Low risk |
| Brown 2005 | 2 | 2 | 2 | 6 | Moderate risk |
| Ige 2012 | 3 | 2 | 3 | 8 | Low risk |
| Okoromah 2012 | 2 | 2 | 2 | 6 | Moderate risk |
| Miller 2013 | 3 | 2 | 3 | 8 | Low risk |
| Chelo 2015 | 3 | 2 | 3 | 8 | Low risk |
| Arodiwe 2016 | 2 | 2 | 2 | 6 | Moderate risk |
| Namuyonga 2016 | 3 | 2 | 3 | 8 | Low risk |
| Sanyahumbi 2017 | 3 | 2 | 3 | 8 | Low risk |
| Majonga 2018 | 3 | 2 | 3 | 8 | Low risk |
| McCrary 2018 | 4 | 2 | 3 | 9 | Low risk |
| Manafe 2019 | 2 | 2 | 2 | 6 | Moderate risk |
| Frigati 2019 | 4 | 2 | 3 | 9 | Low risk |
| Mahtab 2020 | 4 | 2 | 3 | 9 | Low risk |
| McCrary 2020 | 4 | 2 | 3 | 9 | Low risk |
| Duru 2020 | 2 | 2 | 2 | 6 | Moderate risk |
| Majonga 2020 | 3 | 2 | 3 | 8 | Low risk |
| Wubayehu 2020 | 3 | 2 | 3 | 8 | Low risk |
| Arodiwe 2023 | 2 | 2 | 2 | 6 | Moderate risk |
| Garba 2023 | 3 | 2 | 3 | 8 | Low risk |
Meta analysis of the prevalence of cardiac dysfunction
As shown in Fig. 2, This meta-analysis included 20 studies comprising 3,994 children living with HIV across Sub-Saharan Africa. Reported prevalence of LVSD varied widely, ranging from 0.2% in contemporary ART-era cohorts to over 30% in earlier studies. Using a random-effects model, the pooled logit-transformed estimate corresponded to an overall prevalence of 6% (95% CI: 3%–12%), however, heterogeneity was extremely high (I² = 95%, τ² = 2.04), indicating substantial variability between studies. This high heterogeneity indicates that the pooled estimate should not be interpreted as a single representative prevalence for all SSA settings. It reflects differences in study design, ART exposure, population characteristics, and echocardiographic definitions. Egger’s test did not suggest evidence of publication bias or small study effects (p = 0.86; intercept: -6.86).
Fig. 2.
Forest Plot illustrating the pooled prevalence of LVSD in children living with HIV in SSA
Sensitivity analysis excluding one study, which used a stricter FS threshold [22], did not materially change the pooled prevalence estimate (5.6%, 95% CI: 2.9–10.4%) compared with the primary analysis (6.0%, 95% CI: 3.0–12%). Sub-group meta-analysis demonstrated substantial differences across study characteristics. Pre-ART studies showed a markedly higher pooled prevalence of LVSD compared with ART-era studies (27.8% vs. 3.6%). Similarly, studies using fractional shortening reported a higher prevalence than those using ejection fraction (18.0% vs. 2.7%).
Study quality also influenced estimates, with moderate-quality studies reporting higher prevalence than high-quality studies (17.9% vs. 3.2%). These findings suggest that both clinical and methodological factors contribute significantly to between-study heterogeneity. Table 3 provides a summary of the subgroup meta-analyses findings. The Funnel plot and subgroup forest plots are provided as supplementary Figs. 1–6.
Table 3.
Sub-group meta-analysis of study-level factors associated with LVSD
| Analysis | Subgroup | Studies | Pooled prevalence | 95% CI | I² |
|---|---|---|---|---|---|
| Overall | All studies | 20 | 6.00% | 3.00–12.00 | 95.1% |
| ART era | Pre-ART/early ART | 4 | 27.80% | 15.10–45.40 | 94.2% |
| ART era | 16 | 3.60% | 2.00–6.40 | 88.8% | |
| Method* | FS | 7 | 18.00% | 8.40–34.50 | 92.7% |
| EF | 12 | 2.70% | 1.60–4.50 | 70.9% | |
| Study quality | Low Risk | 14 | 3.20% | 1.40–6.96 | 96.1% |
| Moderate Risk | 6 | 17.90% | 11.50–26.80 | 76.5% | |
| ART coverage | < 80% on ART | 5 | 12.80% | 4.20–32.60 | 96.4% |
| ≥ 80% on ART | 12 | 2.60% | 1.40–4.70 | 74.4% | |
| AIDS proportion | < 50% AIDS | 9 | 11.30% | 5.20–22.70 | 94.2% |
| ≥ 50% AIDS | 4 | 1.73% | 0.10–18.60 | 96.3% |
*Total number of studies for Method is 19 as one study which applied a stricter definition for LVSD (FS < 25%) was included in the main analysis but excluded from the subgroup analysis
Meta-regression analysis demonstrated that higher ART coverage was significantly associated with lower LVSD prevalence. It demonstrated that each 10% increase in the proportion of participants receiving ART was associated with an approximately 25% reduction in the odds of reported LVSD prevalence across studies (OR 0.75, 95% CI 0.61–0.94). Studies conducted in the ART era also demonstrated substantially lower odds of reported LVSD prevalence compared with pre-/early-ART studies. Echocardiographic method significantly influenced estimates, with Studies defining LVSD using fractional shortening reporting approximately 8-fold higher odds of LVSD prevalence compared with studies using ejection fraction criteria. Study quality was also associated with variability in reported prevalence. The proportion of participants in the studies who had AIDs demonstrated a non-statistically significant relationship with reported prevalence.
The meta-regression analysis is reported in Table 4 below:
Table 4.
Meta-regression summary of study-level factors associated with LVSD
| Variable | Studies (n) | Co-efficient | SE | Z | OR | 95% CI | p-value | Interpretation |
|---|---|---|---|---|---|---|---|---|
| ART % (per 10% increase) | 17 | -0.29 | 0.11 | -2.58 | 0.75 | 0.60–0.93 | 0.01 | Higher ART coverage associated with lower LVSD prevalence |
| AIDS % (per 10% increase) | 13 | -0.30 | 0.18 | -1.65 | 0.74 | 0.52–1.06 | 0.10 | No significant relationship |
| ART era (pre-ART REF) | 20 | -2.31 | 0.62 | -3.75 | 0.10 | 0.03–0.33 | < 0.001 | Significant reduction in LVSD in the ART era |
| Echocardiographic method (EF REF) | 19 | 2.16 | 0.48 | 4.46 | 8.67 | 3.35–22.38 | < 0.001 | FS yields higher prevalence estimates |
| Study quality (moderate REF) | 20 | -1.79 | 0.64 | -2.80 | 0.17 | 0.05–0.58 | 0.005 | Higher-quality studies report lower prevalence |
Other Risk Factors for cardiac dysfunction in children living with HIV in SSA
Other risk factors identified in some of the studies are summarized narratively in Table 5. Left ventricular systolic dysfunction in HIV-infected children in sub-Saharan Africa was also noted to be associated with advanced HIV disease, low CD4 counts, malnutrition, anaemia, and late initiation of ART. Older age, longer duration of untreated HIV, and exposure to certain ART drugs also appeared to show some association with LVSD while early initiation and long-term ART appeared to be associated with lower prevalence. Additional contributors such as socio-economic vulnerability also played significant roles, highlighting the multifactorial nature of cardiac involvement in this population.
Table 5.
Summary of Risk Factors for Cardiac Dysfunction in HIV-Infected Children in Sub-Saharan Africa
| Risk Factor | Description / Key Findings | Supporting Studies |
|---|---|---|
| Advanced HIV Disease (WHO Stage III/IV) & Low CD4 Count | Severe immunosuppression and advanced disease strongly linked to LVSD and other cardiac abnormalities. LVSD prevalence highest among children with AIDS (81%), compared to milder HIV (27%). Lower CD4 count independently predicts dysfunction. | 8,9,12,26,34 |
| Older Age & Longer Duration of HIV Infection | LVSD and other cardiac abnormalities appear to be more common with age and longer duration of untreated infection. Adolescents show higher rates than younger children. | 2,10,12,28,33 |
| Shorter Duration on ART (Late ART Initiation) | Early, sustained ART appears to be associated with lower LVSD prevalence. Later or interrupted ART is linked with higher LVSD rates. | 9,12,24,29 |
| Malnutrition, Low BMI, Growth Failure | Growth failure, low weight-for-age, and low BMI are associated with higher LVSD prevalence. | 9,12,23,29,34 |
| Anaemia (Low Haemoglobin) | Children with very low haemoglobin are more likely to develop LVSD. | 9,12, 29,34 |
| ART Drug-Specific Effects | Zidovudine exposure is associated with abnormal LV mass and impaired strain. | 2,10,28 |
| Long-Standing Viral Replication / Poor Viral Control | Poorly controlled viral load contributes to myocardial inflammation and dysfunction; long-term ART suppression appears to be associated with lower reported prevalence. | 10,12,28,36,31 |
| Sex (Male Gender) | Some studies noted higher LV mass or LVSD among males, although findings were inconsistent. | 2,10 |
| Socio-economic & Environmental Stressors | Poverty, limited access to healthcare, and late diagnosis indirectly increase risk of severe disease and associated cardiac involvement. | 8,9,27 |
-
Advanced HIV Disease and Immune Suppression
Advanced HIV disease marked by severe immunosuppression (low CD4 counts) and WHO stage III/IV illness was found to be associated with LVSD. In Nigeria, Arodiwe et al. [12]. found that LV systolic dysfunction (LVSD) occurred in 81% of children with AIDS compared with 27% of HIV-infected children without AIDS, and just 2% of controls. Lower CD4 count also independently predicted LVSD [12]. A similar pattern was reported from a study in Lagos by Okoromah et al. [8] where LVSD was most common in children with advanced clinical disease. Studies from Uganda [9, 26] and Ethiopia [34] also reported higher proportions of LVSD in children with lower historical CD4 counts.
-
Age, Duration of HIV Infection, and ART Exposure Time
Multiple of the included studies indicated that older age and longer lifetime HIV exposure were associated with increased myocardial abnormalities. Arodiwe et al. [12] reported a positive correlation between age and LVSD, while longer duration on ART appeared to be associated with lower reported prevalence. Kenyan cohorts [10, 28] showed that subclinical systolic strain abnormalities accumulated with age, especially in persons with perinatally acquired HIV, suggesting a role for chronic infection on LVSD even with virological control.
-
Nutritional Status, Growth Failure, and Anaemia
Poor nutritional status and anaemia have also been found to contribute to LVSD. In Mozambique, Manafe et al. [29] found that children who later developed LVSD had very low baseline haemoglobin. Similar findings were reported by Wubayehu [34].
-
Antiretroviral Drug Exposure
Exposure to certain ART drugs was associated, as cumulative zidovudine exposure appeared to be associated with subclinical myocardial strain abnormalities [10, 28] However, most other studies, including Arodiwe [12] and Manafe [29], observed that longer duration on effective ART appeared to be associated with lower reported prevalence of LVSD.”
Discussion
This review aimed at determining the prevalence of cardiac dysfunction in children living with HIV in Sub-Saharan Africa and investigating the associated risk factors. The review indicates that LVSD remains present in children living with HIV, but the pooled prevalence of 6.0% should not be interpreted as a single summary estimate applicable to all settings across the region. The combination of high heterogeneity (I²=95%), prevalence estimates ranging from 0.2% to 50%, and strong subgroup dispersion indicates that the pooled estimate is best interpreted cautiously.
Subgroup analysis and meta-regression were done to further investigate the high heterogeneity found, and they showed that studies from the pre-ART/early ART era reported far higher prevalence than contemporary ART-era cohorts. This trend has also been reported in studies from other regions.
One of the earliest studies on LVSD in children living with HIV found a prevalence of LVSD of 100% in a small American cohort of eight HIV-infected children who all had advanced disease [37]. Other pre-ART era studies from Brazil [38], Thailand [39], and India [40] also had a high prevalence of LVSD (35–37%) in HIV-infected children. Conversely, and similar to our review, later modern-era ART studies have found much lower prevalence values of LVSD of 5–8% [41–43]. In contrast, a large global adult review by Erqou et al. [44] reported a much higher pooled prevalence of 12.9% for LVSD. The review, however, also noted a trend towards lower prevalence in more recently published studies and studies reporting higher ART use.
Lower ART coverage was also associated with higher rates of LVSD, and each 10% increase in ART coverage was associated with lower odds of LVSD. These patterns are biologically and clinically plausible, and they support the interpretation that sustained treatment may mitigate myocardial injury. We would, however, note that ART era, ART coverage, duration of therapy, and disease severity are interrelated variables, so the apparent association of sustained ART with reduced prevalence of LVSD may partly capture earlier diagnosis, lower cumulative viraemia, better nutritional support, and broader improvements in paediatric HIV care. The non-significant association for AIDS percentage in meta-regression further argues against simplistic causal interpretation and suggests residual confounding rather than a direct inverse relationship between disease severity and LVSD, as was suggested by subgroup analysis.
The observed reduction in LVSD prevalence in more recent studies likely reflects multiple interacting factors, including earlier HIV diagnosis, expanded ART coverage, improved virologic suppression, enhanced nutritional support, and broader access to paediatric HIV care over time [45]. Differences in healthcare infrastructure and access to specialized cardiovascular assessment between settings may also contribute to variability in reported prevalence [1]. Survivorship bias may also partly influence temporal comparisons, as children with severe, untreated HIV and advanced cardiac disease, particularly in the earlier years of the pandemic, may have experienced higher mortality before long-term follow-up or cardiac evaluation became feasible [46]. The evolution of paediatric HIV management, including routine viral load monitoring, earlier ART initiation, and improved prevention of opportunistic infections, has likely substantially reduced the burden of HIV-associated myocardial dysfunction in contemporary cohorts [30, 44].
Measurement heterogeneity is another major source of variability. FS-based studies reported substantially higher prevalence than EF-based studies, and the method meta-regression showed a large effect size in the same direction. The substantially higher prevalence observed in FS-based studies likely reflects methodological differences between FS and EF assessment. FS is more load-dependent and susceptible to measurement variability, including regional wall motion abnormalities, than EF, potentially increasing the detection of mild systolic abnormalities [47]. This may lead to overestimation or underestimation of true LV systolic function. Additionally, many earlier studies may have relied primarily on FS because of limited echocardiographic resources and older imaging protocols. The American Society of Echocardiography [48] (ASE) includes both SF and EF in its standard quantification tools and recommends standardized imaging protocols and reporting structures to improve reproducibility. However, earlier versions of the ASE guidelines did allow for the use of FS only for the evaluation of systolic function in children [49], and this reflected in the finding that it was mostly earlier studies that applied FS only. In the present review, this difference likely reflects both true differences in measurement properties and inconsistent implementation across centres, reinforcing the need for harmonized definitions in future work.
This review is, to the knowledge of the authors, the first review on LVSD in children infected with HIV in the region.
Implications of the Findings
Screening/treatment
The data from our review support heightened cardiovascular vigilance in children and adolescents with advanced or previously advanced HIV, incomplete ART exposure, persistent viraemia, anaemia, malnutrition, cardiopulmonary symptoms, or prior exposure to older regimens of concern. They do not, however, prove the need for blanket echocardiographic screening to improve outcomes.
These findings also reinforce the imperative of early ART initiation and sustained viral suppression as long-term strategies for control of comorbidities such as LVSD in paediatric HIV, particularly considering that only 57% of children living with HIV compared with 77% of adults were on ART in 2023 [1].
Control programmes at national or sub-national levels can include risk-based cardiac assessment to be embedded within routine HIV care. Symptom checklists, blood pressure measurement, nutritional and haemoglobin assessment should be applied with referral for echocardiography when risk signals or symptoms are present. Broader holistic care for non-infectious comorbidities to address good nutrition, anaemia, and respiratory disease alongside ART optimization is advocated.
Health systems, research and policy
Health systems may benefit from strengthening referral pathways between HIV clinics and cardiology services, improving diagnostic capacity, and training clinicians to recognise clinical signs that may suggest cardiac dysfunction.
Future research should move beyond cross-sectional studies toward longitudinal cohorts of children started early on current WHO-preferred suppressive regimens, using standardized echocardiographic case definitions. Mechanistic studies linking inflammation, nutrition, and ART exposure to myocardial phenotypes are also recommended, as are pragmatic trials testing whether targeted screening changes management or outcomes.
Limitations of the review
This review was limited by the restriction to English-language studies, which may have excluded relevant evidence published in French or Portuguese within Sub-Saharan Africa.
Heterogeneity across studies was extremely high (I² = 95%), although this was partially explained by study-level characteristics in the subgroup analysis and meta-regression.
Most of the included studies were cross-sectional, so temporality and prognosis cannot be established.
The evidence base also spans broad age ranges and studies incompletely reported modes of HIV acquisition and LVSD severity. Such risk factors/outcomes could therefore not be adequately synthesised or investigated.
Finally, although Egger’s test was non-significant and did not suggest small-study effects, the associated high heterogeneity itself may produce small-study effects.
Conclusion
LV systolic dysfunction remains present in a persistent proportion of children living with HIV in Sub-Saharan Africa, although prevalence varies widely across settings and treatment eras. The findings highlight the importance of early ART initiation and consideration of targeted cardiovascular assessment in higher-risk groups. There is a need for longitudinal studies using standardised echocardiographic definitions to clarify the clinical significance and optimal management of LVSD in this population.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
The authors would like to acknowledge Mr. David Innocent who provided training and technical support for the technical aspects of data extraction and meta-analysis. The authors used ChatGPT (OpenAI) to assist with language editing, formatting and statistical code debugging. All AI-generated content was independently reviewed and verified by the authors, who retained full responsibility for the study design, data analysis, interpretation, and final manuscript content.
Abbreviations
- HIV
Human Immunodeficiency Virus
- LVSD
Left Ventricular Systolic Dysfunction
- ART
Antiretroviral therapy
- AIDS
Acquired Immune Deficiency Syndrome
- EF
Ejection Fraction
- FS
Fractional Shortening
- NOS
Newcastle Ottawa Scale
Author contributions
KB conceptualised the study and wrote the background, did the search and data extraction. MM and CN contributed to the background and methodology and supervised the search and data extraction and edited the final manuscript. IE did the searches and data extraction and contributed to the writing of the final manuscript.
Funding
This review was entirely funded by the authors. No institutional funding or other support was obtained for the study. By submitting our article, we agree to pay the APC in full if our article is accepted for publication (unless it is covered by an institutional agreement or journal partner, or a full waiver has been granted).
Data availability
Data was generated in the course of this research. All datasets generated and analysed which are not within the body of the article are available on request to the corresponding author.
Declarations
Ethical approval and consent to participate
As no original data collection from human subjects was done, ethical review and consent to participate were not applicable.
Consent for publication
Not applicable.
Dual publication
The results/data/figures in this manuscript have not been published elsewhere, nor are they under consideration by another publisher.
Third party material
All the material is owned by the authors, and/or no permissions are required.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data was generated in the course of this research. All datasets generated and analysed which are not within the body of the article are available on request to the corresponding author.