There has been a decrease in many opportunistic infections among HIV-positive children in low- and middle-income countries thanks to antiretroviral therapy, a meta-analysis shows, reports aidsmap. Investigators estimated that use of antiretroviral therapy (ART) is averting over 161,000 opportunistic infections each year, saving $17m per annum.
“This systematic review based on study data from a > 20 year period shows an overall trend of reduced incidence and prevalence for most opportunistic infections (OIs) after ART initiation, and substantial impact and cost savings on OIs averted with earlier ART initiation,” comment the authors.
“This systematic review and meta-analysis is the most comprehensive assessment of incidence and prevalence of the 14 most important OIs and other infections and the effect of ART among HIV-infected children in (low- and middle-income countries).”
An estimated 2.6m children worldwide are infected with HIV, the overwhelming majority (88%) of whom live in sub-Saharan Africa. Scale-up of ART in low- and middle-income countries has been less successful in children compared to adults. It’s been estimated that only a third of ART-eligible children are currently receiving therapy compared to two-third of adults.
Incidence of opportunistic infections among HIV-infected children in richer countries declined significantly after the introduction of ART. However, less is known about the continuing burden of opportunistic infections among HIV-infected children in less wealthy settings. A clearer understanding of this important question is needed so that appropriate interventions can be designed.
An international team of investigators led by Marie-Renée B-Lajoie at the Jewish General Hospital, Montreal and assistant professor, department of family medicine, McGill University, therefore conducted a systematic review and meta-analysis to evaluate the incidence and prevalence of 14 common HIV-related opportunistic infections and other infections and the impact of ART among HIV-positive children (aged under 18) in sub-Saharan Africa, Asia and Latin America.
Studies involving at least 50 HIV-positive children conducted between 1990 and 2013 and reporting on incidence and/or prevalence of at least one of 14 common HIV-related opportunistic infections were eligible for inclusion.
The risk of opportunistic infections for ART-naïve and ART-experienced children was calculated. Using 2010 WHO treatment guidelines (treatment for all HIV-positive children aged under two years; for 2 to 4 years olds with a CD4 percentage below 25%; for 5-14 year olds with a CD4 count below 350 cells/mm3), the investigators also estimated the number of opportunistic infections and money saved due to the scale-up of ART.
A total of 88 studies involving approximately 66,000 children were included.
Incidence of opportunistic infections was reported in 35 studies. The most common infections in ART-naïve children were bacterial pneumonia (25%), pulmonary TB (10%), oral and oesophageal thrush (8%) and extra-pulmonary TB (7%). A similar profile of disease was observed among ART-treated children, with bacterial pneumonia (22%), TB (9%) and varicella zoster (8%) the most common.
Prevalence was examined in 60 studies. The most prevalent infections were bacterial pneumonia (33%), oral and oesophageal thrush (25%) and sepsis (23%). Use of ART had a dramatic impact on the incidence of several infections, especially Cryptosporidium diarrhoea (OR, 0.10; 95% CI, 0.05-0.22), toxoplasmosis (OR, 0.33; 95% CI, 0.13-0.43) and extra-pulmonary TB (OR, 0.15; 95% CI, 0.10-0.21).
The investigators estimated that use of ART prevented 161,000 opportunistic infections annually, saving a total of $17,700,000 each year. More than 90% of the savings came from the averted cases of TB.
The authors note that since 2015 WHO guidelines have recommended ART for all HIV-infected children. “This is critical as scale-up of ART has been successful in children,” they conclude. “Strong mother-child prevention programs, expansion of access to early infant diagnosis, and more robust procurement and supply management systems, including improved paediatric ART formulation, are also critical to reducing the adult-paediatric ART coverage gap, with an ultimate goal of eliminating the paediatric HIV burden.”
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 ( Methods: Eligible studies described the incidence of OIs and other infections in ART-naïve 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-naïve 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.
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-naïve 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.
Marie-Renée B-Lajoie, Olivier Drouin, Gillian Bartlett, Quynh Nguyen, Andrea Low, Georgios Gavriilidis, Philippa Easterbrook, Lulu Muhe