Prevalence of pretreatment drug resistance in persons initiating and reinitiating antiretroviral therapy in Sri Lanka: results from a national representative survey.

BACKGROUND: We conducted a nationwide cross-sectional study to estimate pretreatment drug resistance (PDR) prevalence in adults initiating ART in Sri Lanka following the WHO's recommendations. METHODS: HIV drug resistance was determined on dried blood spots (DBSs) using population-based sequencing of the protease and reverse transcriptase genes and interpretation was based on Stanford HIVdb v9.0. Analyses were weighted to adjust for multistage sampling and genotypic failure rate. We used logistic regression to assess differences between groups. RESULTS: Overall, in 10% (15 of 150) of patients initiating ART, HIV drug resistance mutations were detected. The prevalence of resistance to NNRTI drugs efavirenz/nevirapine was 8.4% (95% CI 4.6-15.0) but differed among those reporting having prior antiretroviral (ARV) exposure (24.4%, 95% CI 13.8-39.5) compared with 4.6% (95% CI 1.6-12.8) for those reporting as being ARV naive (OR 4.6, 95% CI 1.3-16.6, P = 0.021). PDR to efavirenz/nevirapine was also nearly twice as high among women (14.1%, 95% CI 6.1-29.4) compared with men (7.0%, 95% CI 3.1-14.7) (P = 0.340) and three times high among heterosexuals (10.4%, 95% CI 2.4-35.4) compared with MSM (3.8%, 95% CI 1.1-12.7) (P = 0.028). NRTI PDR prevalence was 3.8% (95% CI 1.1-12.1) and no PI PDR was observed in the study. CONCLUSIONS: A high prevalence of efavirenz/nevirapine PDR was reported, especially in patients with prior ARV exposure, in women and those reporting being heterosexual. These findings highlight the need to fast-track the transition to the WHO-recommended dolutegravir-based first-line ART.

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 PMTCT-unexposed children (P = 0.004). The PDR prevalence in PMTCT-unexposed children increased from 0% 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.