Béatrice DAMBAYA1 , Joseph FOKAM1 , Ezechiel NGOUFACK JAGNI SEMENGUE2*, Désiré Augustin TAKOU KOMEGO1 , Georges TETO1 , Grace Odile BELOUMOU ANGONG1 , Linda Chapdeleine MEKOUE MOUAFO2 , Nelly KAMGAING1 , Samuel Martin SOSSO1 , Serge Clotaire BILLONG3 , Anne Esther NJOM NLEND4 , Martin SOBZE SANOU2, Celine NKENFOU1 , Paul KOKI1 , Flobert NJIOKOU3 , Vittorio COLIZZI5 , Carlo Frederico PERNO6 , Alexis NDJOLO1
1Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB) ; 2Faculty of Medecine and Pharmaceutical sciences, University of Dschang ; 3Faculty of medecine and Biomedical sciences, University of Yaoundé 1 ; 4National Social Welfare Hospital, Yaounde ; 5UNESCO Chair of Multidisciplinary Biotechnology,University of Rome Tor Vergata; 6University of Milan
CaHReF 2018, Yaoundé Congres hall, 08 – 11 January 2019 , OSME051
Background: HIV-1 vertically infected children stand at high risk of HIV drug resistance (HIVDR), especially with failure to prevention of mother to child transmission and pediatric antiretroviral therapy (ART). Thus, surveillance of pediatric HIVDR in a context like Cameroon might contribute in delineating optimal regimens with respect to children therapeutic profile.
Objectif: We evaluated the threshold of HIVDR and subtypes distribution among drug-na'à¯ve and virologically failing (1000copies/ml) HIV-1 vertically infected children and adolescents in Cameroon.
Methodology: A cross-sectional and analytical study was conducted throughout the year 2017 on samples from 60 children and adolescents (15 drug-na'à¯ve versus 45 experiencing virological failure [VF]) monitored for HIVDR at the Virology Laboratory of the Centre International de Reference Chantal BIYA (CIRCB), Yaounde-Cameroon. Genotypic HIVDR testing was performed in the protease-reverse transcriptase regions using an in-house sequencing protocol. HIVDR was interpreted using the Stanford algorithm V8.5, HIV-1 subtyping was performed using BioEdit v7.2.6 for sequence alignment and MEGA v7.0.26 for tree construction. Data were analysed using the CIRCB-HIVDR database, Microsoft Access and Excel 2013; with P <0.05 considered statistically significant.
Results: Median-age was 8months[IQR:4 –26] for drug-na'à¯ve and 143months[IQR:114 –184] for those experiencing VF, with ART-duration of 23.55months[IQR:7.61 –60.91]; 64.4%(29/45) being on non-nucleoside RT inhibitors (NNRTI) versus 35.6%(16/45) protease-inhibitor (PI/r)-based regimens. Among drug-na'à¯ve, overall HIVDR-threshold was 53.3% (8/15) including 5/8 reported PMTCT-exposed, with 33.3%(5/15) to NNRTI, 26.7%(4/15) to NRTI and 13.3%(2/15) to PI/r. At VF, overall HIVDR-threshold was 97.8%(44/45), with 95.6%(43/45) to NNRTI, 91.1%(41/45) to NRTI and 17.8%(8/45) to PI/r. Importantly, multi-drug resistance was found in 20%(3/15) drug-na'à¯ve versus 86.2%(25/29) NNRTI-based and 50%(8/16) PI-based regimens; OR=5, P=0.048. HIV-1 subtype distribution was CRF02_AG (66.7%), G(8.3%), F2(5%) and others(20%); without any significant association to HIVDR(P=0.36).
Conclusion/Recommandation: Among drug-na'à¯ve infants/children, HIVDR may be high, likely driven by pediatric-infection following PMTCT-exposure, coupled to HIVDR-testing at early-age. Pediatric-ART leads to early VF (~24months) and very high HIVDR, with significant multi-drug resistance requiring innovative drug-class based-regimens. Henceforth, for drug-na'à¯ve infants/children (without PMTCT-exposure), ART-initiation with PI-based regimens should be emphasized. In contrast, pediatric-infection with PMTCT-exposure or experiencing ART-failure should receive ART guided by resistance profiling. Subtyping effects on HIVDR merits further investigations.
Key Words: ART, HIVDR, Genetic diversity, Pediatrics, Cameroon