Pretreatment HIV Drug Resistance Rises in Sub-Saharan Children

The results of a systematic review and meta-analysis of the literature on pretreatment HIV drug resistance (PDR) in children in sub-Saharan African showed that it increased substantially, particularly in children with prenatal exposure to antiretroviral drugs for the prevention of mother-to-child transmission (PMTCT).

For the study, published in the Journal of Antimicrobial Chemotherapy, the investigators searched the medical literature through May 2016 for studies on PDR in children in sub-Saharan Africa, ultimately including original studies reporting the proportion of children (median age, ≤12 years) with PDR in any country in sub-Saharan Africa in the meta-analysis. For the purposes of the study, the investigators defined PDR as “[HIV drug resistance] to any drug class, detected by genotypic resistance testing, in children who have not yet initiated first-line [antiretroviral therapy (ART)], with or without previous exposure to PMTCT.” Articles about acquired drug resistance and articles in which PDR was not reported separately for children and adults were excluded. Nineteen studies that included 2617 children from 13 countries ultimately met the qualifications for inclusion.

Results of the meta-analysis, conducted with a random-effects model, showed a pooled PDR prevalence of 42.7% (95% confidence interval [CI], 26.2% to 59.1%) in PMTCT-exposed children and 12.7% (95% CI, 6.7% to 18.7%) among PMTCT-unexposed children (P =.004), a 4-fold difference. The PDR prevalence in PMTCT-unexposed children increased from 0% in 2004 to 26.8% in 2013 (P =.009). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were present in 32.4% (95% CI, 18.7% to 46.1%) and 9.7% (95% CI, 4.6% to 14.8%) of PMTCT-exposed and unexposed children, respectively. The incidence of PDR was greater in children younger than 3 years vs children aged 3 years (40.9% [95% CI, 27.6% to 54.3%] and 17.6% [95% CI, 8.9% to 26.3%], respectively; P =.025). Protease inhibitor (PI) mutations were infrequent (<2.5%).

In an email interview, lead investigator Ragna Boerma, MD, from the Amsterdam Institute for Global Health and Development & Department of Global Health and the Global Child Health Group, Emma Children’s Hospital, Academic Medical Center of the University of Amsterdam, The Netherlands, told Infectious Disease Advisor that it was important to study the prevalence of PDR in sub-Saharan children because most of them receive first-line treatment with a NNRTI-based ART regimen, against which resistance is known to develop rapidly. This approach places patients at risk for early treatment failure and further accumulation of drug resistance mutations. “[The World Health Organization] recommends that children <3 years of age do not start with an NNRTI-based regimen, but with a PI-based regimen, against which resistance develops less frequently,” she noted. “However, many African countries have not yet adopted these guidelines, because PIs are more expensive. So in terms of clinical implications, our data stress the importance of starting a PI-based regimen for all children <3 years as recommended by [the World Health Organization], but not put in practice yet in many ART clinics. In older children, PI-based first-line ART needs to be considered as well, because of the high prevalence of PDR against NNRTIs.”

Reference

Boerma RS, Sigaloff KCE, Akanmu AS, et al. Alarming increase in pretreatment HIV drug resistance in children living in sub-Saharan Africa: a systematic review and meta-analysis. J Antimicrob Chemother. 2016;72:365-371. doi:10.1093/jac/dkw463.