High Resistance Mutation to cART in HIV-1 Exposed Infected Children and Recent Emergence of CRF02_AG Variant in Bouar, A Rural Environment of Central African Republic
Abstract
Introduction: The emergence of HIV-1 recombinant forms and drug combined antiretroviral therapy (cART) resistance are frequent in the therapeutic course of HIV-infected children in Low and Middle-Income Countries (LMIC) precisely in Central African Republic (CAR) as evidenced by studies carried out in the Bangui capital. Vertical tran-smission rate including breastfeeding is 12.4. The aim is to analyze retrospectively the molecular characterization of sequencing results and mutation detected in HIV infected children under cART since infancy.
Methods: The 2019 retrospective review of the clinical, therapeutical, and immunological-molecular records of six children who were performed the genome sequencing, followed in Bouar, at the St Michel IST/HIV Center, in the north-west of the CAR. These perinatal HIV-infected children were not tested early and started late cART regimens, used for vertical transmission prevention and treatment initiation of HIV infection in CAR.
Results: We analyzed results from viral RNA extracted amplification and sequencing of 6 children plasma samples collected under first line ART. Sequencing of viral genomes revealed high level resistance mutations to NRTIs (ABC/FTC/3TC) and to NNRTIs (EFV/NVP used locally and DOR/ETR/ RPV unused) with ambiguous positions in amino-acids comparison and deletion. Three CRF02_AG strains formed a cluster by strongly detaching from other CAR and worldwide strains with robust boostrap at 91.
Conclusions: The genomes sequencing showed that resistance mutations made the treatment inefficient confirming the clinical, immunological, and virol-ogical failure and an emerging CRF02_AG genotype variant, probably of foreign origin. This discovery clearly highlights the importance of ART genetic resistance testing and personalized medicine.
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