ART use averting huge numbers of opportunistic infections among children living with HIV in lower-income countries

There has been a decrease in cases of many opportunistic infections (OIs) among children living with HIV in low- and middle-income countries thanks to antiretroviral therapy (ART), a meta-analysis published in the June 15^th edition of Clinical Infectious Diseases shows. Investigators estimated that use of ART is averting over 161,000 opportunistic infections each year, saving $17 million 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 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 2.6 million children worldwide are living 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 children with HIV in richer countries declined significantly after the introduction of ART. However, less is known about the continuing burden of opportunistic infections among HIV-positive 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 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 children living with HIV (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 World Health Organization (WHO) treatment guidelines (treatment for all HIV-positive children aged under two years; for 2 to 4 year olds with a CD4 percentage below 25%; for 5 to 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 esophageal 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 children living with HIV. “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 pediatric ART formulation, are also critical to reducing the adult-pediatric ART coverage gap, with an ultimate goal of eliminating the pediatric HIV burden.”