Alarming increase in pretreatment HIV drug resistance in children living in sub-Saharan Africa: A systematic review and meta-analysis

Background: Children have an augmented risk of pretreatment HIV drug resistance (PDR) due to exposure to antiretroviral drugs for the prevention of mother-to-child transmission (PMTCT). Paediatric data are essential to evaluate the effectiveness of the restricted number of paediatric regimens currently available, but these data are scarce. Methods: We conducted a systematic review of the literature on PDR in children (median age≤12 years) in sub- Saharan Africa. We separately extracted the proportion of children with PDR for children with and without prior PMTCT exposure, used random-effects meta-analysis to pool proportions and used meta-regression to assess subgroup differences. Results: We included 19 studies representing 2617 children from 13 countries. The pooled PDR prevalence was 42.7%(95%CI 26.2%-59.1%) among PMTCT-exposed children and 12.7% (95% CI 6.7%-18.7%) among PMTCTunexposed children (P=0.004). The PDR prevalence in PMTCT-unexposed children increased from0% in 2004 to 26.8% in 2013 (P=0.009). NNRTI mutations were detected in 32.4% (95% CI 18.7%-46.1%) of PMTCT-exposed children and in 9.7% (95% CI 4.6%-14.8%) of PMTCT-unexposed children; PI mutations were uncommon (<2.5%). PDR was more common in children aged<3 years compared with children aged ≥3 years [40.9% (95% CI 27.6%-54.3%) versus 17.6% (95%CI 8.9%-26.3%), respectively (P=0.025)]. Conclusions: The PDR prevalence in African children is high and rapidly increasing. Even in PMTCT-unexposed children, the most recent reports indicate that PDR is present in up to a third of children starting first-line therapy. Our data underscore the importance of initiating PI-based first-line ART in young children (<3 years of age) and suggest that older children may also benefit from this approach.