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 transmission rate including during breastfeeding is 12.4. The aim of study is to analyze retrospectively the molecular characterization of sequencing results and mutation detected in HIV infected children who have received cART initiated 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 and HIV Center, in the north-west of the CAR. These children infected with HIV perinatally had their seropositive test performed at a median age of 6 years and initiated cARTs at an average age of 7 years as part of treatment regimens also used for the prevention of vertical transmission and the initiation of treatment for HIV infection in CAR. Results: We analyzed results from viral RNA extracted amplification and sequencing of 6 children plasma samples collected under first line antiretroviral therapy. Persistent opportunist infections confirmed Immunosuppression in all patients. Sequencing of viral genomes revealed high level resistance mutations to NRTIs (ABC, FTC and 3TC) in five patients and to NNRTIs (EFV, NVP used locally and DOR, ETR and RPV unused) for all with ambiguous positions in amino-acids comparison and deletion. The HIV-1 group M found in these patients were sub-type A (1) and G-J (1), and CRF02_AG (4), respectively. Three CRF02_AG strains formed a variant cluster by strongly detaching from other CAR and worldwide strains with robust boostrap at 91. Retention and adherence were complicated by the cART limited number and laboratory tests, the irregular supply, and the remoteness of patients from the Center. Conclusions: The genomes sequencing showed that resistance mutations made the treatment inefficient confirming the observed virological and immunological failure. The CRF02_AG genotype is an emerging variant, probably of foreign origin. This discovery clearly highlights the importance and the necessity of ART genetic resistance testing and personalized medicine.