Substantial drop in opportunistic infections in children with ART

Incidence and prevalence of opportunistic and other infections and the impact of antiretroviral therapy among HIV-infected children in low and middle-income countries: a systematic review and meta-analysis. 

B-Lajoie MR, Drouin O, Bartlett G, Nguyen Q, Low A, Gavriilidis G, Easterbrook P, Muhe L. Clin Infect Dis. 2016 Mar 21. pii: ciw139. [Epub ahead of print]

Background: We conducted a systematic review and meta-analysis to evaluate the incidence and prevalence of 14 opportunistic infections (OIs) and other infections as well as the impact of antiretroviral therapy (ART) among HIV-infected children (<18 years) in low and middle-income countries (LMIC), to understand regional burden of disease, and inform delivery of HIV services.

Methods: Eligible studies described the incidence of OIs and other infections in ART-naive and exposed children from January 1990 to November 2013, using Medline, Global Health, Embase, Cinahl, Web of Knowledge and Lilacs databases. Summary incident risk and prevalent risk for each OI in ART-naive and ART-exposed children were calculated, and unadjusted odds ratios calculated for impact of ART. The number of OI cases and associated costs averted were estimated using the AIM model.

Results: We identified 4542 citations, and 88 studies were included, comprising 55 679 HIV-infected children. Bacterial pneumonia and tuberculosis were the most common incident and prevalent infections in both ART-naive and ART-exposed children. There was a significant reduction in incident risk with ART for the majority of OIs. There was a smaller impact on bacterial sepsis and pneumonia, and an increase observed for varicella zoster. ART initiation based on 2010 WHO guidelines criteria for ART initiation in children was estimated to potentially avert more than 161 000 OIs (2013 UNAIDS data) with estimated cost savings of at least USD $17 million per year.

Conclusion: There is a substantial decrease in the risk of most OIs with ART use in HIV-infected children in LMIC, and estimated large potential cost savings in OIs averted with ART use, although there are greater limitations in paediatric data compared to adults.

Abstract  Full-text [free] access

Editor’s notes: The scale-up of programmes to prevent mother-to-child HIV transmission has resulted in a 60% decline in paediatric HIV infections. The scale-up of antiretroviral therapy (ART), however, has been less successful in children, with only a third of eligible children aged under 15 years receiving ART as of 2014. In high-income countries, there has been a substantial decrease in the incidence of most opportunistic infections (OIs) following the introduction of ART. The impact of ART on burden of OIs in low and middle income countries (LMICs) is much less well-understood.

This meta-analysis estimated the incidence and prevalence of 14 key OIs and other infections in children (aged 0-18 years) before and after the introduction of ART across three geographical regions, namely sub-Saharan Africa, Latin America and the Caribbean, and Asia.

The use of ART has resulted in a decline in incidence of all but three infections, namely tuberculosis, pneumonia and candidiasis. These remain the most common incident and prevalent infections in ART-naïve and ART-exposed children. It is important to note that there is a high incidence of lower respiratory infections in children in LMIC regardless of HIV status.

There is a paucity of well-described or large studies in children compared to in adults. There was significant heterogeneity in the studies included in the review, and few studies reported important confounding factors such as use of co-trimoxazole prophylaxis, age at ART initiation and CD4 count. Also, regional differences could not be examined due to a limited number of studies in Latin America and Asia.

Notwithstanding these limitations, ART has resulted in a substantial cost-saving due to the numbers of OIs averted by use of ART. The 2015 WHO guidelines now recommend ART initiation in all children and this is likely to have an even larger impact on the incidence of OIs and mortality. Along with this, strategies to reduce the burden of TB and pneumonia in children are urgently needed.

Comorbidity, HIV Treatment
Africa, Asia, Latin America
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