The rates of virological failure (VF) and HIV-1 drug resistance were evaluated in a cross-sectional study in HIV-1-infected children living in Dakar, and taking antiretroviral treatment (ART) according to WHO recommendations. The plasma HIV-1 RNA load was measured using the Abbott m2000 RealTime HIV-1 assay. The full-length protease gene and partial reverse transcriptase gene were sequenced, and resistance mutations were assessed by reference to the Stanford University HIV drug resistance database. Of 125 included children (median age, 7 years) taking first-line ART for a median duration of 20 months, 82 (66%) showed detectable HIV-1 RNA load, and 70 (56%) met the 2010 revised WHO criteria of VF (defined as plasma HIV-1 RNA load ≥3.7 log(10) copies/ml). Drug resistance results were available for 52 children with plasma HIV-1 RNA load ≥3.0 log(10) copies/ml, and viruses carrying resistance mutations were found in 48 (92%) children. Among these 48, mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs) or non-NRTIs (NNRTIs) were found in 42 (88%) and 47 (99%) children, respectively. The NRTI-resistant viruses harbored the M184V/I (95%), Q151M (2%), and thymidine-analogue mutations (40%), and the NNRTI-resistant viruses harbored the K103N (34%), Y181C (32%), G190A (23%), and K101E (21%) mutations. A high rate (56%) of VF was demonstrated in Senegalese children after 20 months of first-line ART and therapeutic failure was assessed by the presence of antiretroviral drug resistance mutations in 9 out of 10 children in VF. These findings point out the difficulties of optimizing ART in children living in sub-Saharan Africa, and the crucial need of laboratory monitoring reinforcement.
The prevalence of human immunodeficiency virus (HIV) drug resistance mutations (DRMs) was estimated in 25 untreated infants who were living with HIV-1, younger than 13 months and living in Senegal. Antiretroviral DRMs were detected in 8 of 25 (32%) children. Non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs were present in all (100%) children whose viruses harboured DRMs: K103N in 43%; Y181C, K101E and V106M each in 29%; and Y188L in 14%. The D67N thymidine-analogue mutation was observed in only two children whose mothers had received chemoprophylaxis of mother-to-child transmission (MTCT). The proportion of children whose viruses harboured DRMs was then 6.5-fold higher in children whose mother–child couples had received nevirapine (NVP)-based chemoprophylaxis than in other couples without prophylaxis [7 of 13 (53.8%) vs. 1 of 12 (8.3%)]. These findings point to the absolute need to address primary resistance mutations in case of virological failure in young children treated by antiretroviral drugs, and to make more effective treatment regimens available to NVP-exposed infants living with HIV-1 in Senegal.
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