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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

Author(s): Ulrich Vickos, Giovanni Gaiera, Nicola Cotugno, Christelle Luce Bobossi Gadia, Ornella Anne Sibiro Demi, Angelo Sala, Michela Sampaolo, Alain Le Faou, Enzo Boeri

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 transmission 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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