Patterns of pre-treatment drug resistance mutations of very early diagnosed and treated infants in botswana.

Abstract

OBJECTIVE\nTo describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants.\n\n\nDESIGN\nThe Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated ART in the first week of life and evaluated HIV-1 in plasma and peripheral blood mononuclear cells (PBMCs).\n\n\nMETHODOLOGY\nWe analyzed 257 near HIV-1 full-length sequences (nFLS) obtained by Illumina next-generation sequencing from infants near birth. Sanger sequencing of pol was performed for mothers at delivery and children with clinical failure through 96\u200aweeks. DRMs were identified using the Stanford HIV Drug Resistance Database.\n\n\nRESULTS\nIn 27 infants, median PBMC HIV-1 proviral load was 492\u200acopies/mL [IQR: 78, 1246\u200acopies/mL] at a median of 2\u200adays (range 1, 32); 18 (66.7%) had no DRMs detected; 6 (22.2%) had DRMs detected in defective DNA only, and 3 (11.1%) had DRMs in both defective and intact DNA (p\u200a=\u200a0.09). A total of 60/151 (37.7%) defective sequences had at least one DRM: 31.8% NNRTI, 15.2% NRTI, 5.3% PI and 15.5% INSTI associated mutations. In intact sequences, 33/106 (31.1%) had at least 1 DRM: 29.2% NNRTI, 7.5% NRTI, 0.9% PI and 0 INSTI associated mutations. For all 3 infants with intact sequence DRMs, corresponding DRMs occurred in maternal plasma at delivery. Archived DRMs were detectable at a later clinical rebound on only one occasion.\n\n\nCONCLUSION\nDefective HIV-1 cell-associated DNA sequences may overestimate the prevalence of drug resistance among early-treated children. The impact of DRMs from intact proviruses on long-term treatment outcomes warrants further investigation.