The discriminatory ability of pre-treatment HIV-1 low frequency drug resistance variants to predict antiretroviral treatment outcomes (360G-Wellcome-209294_Z_17_Z)

Because of the increasing levels of HIV drug resistance (HIVDR), genotypic resistance testing (GRT) is currently recommended for clinical care in developed settings and for surveillance purposes in resource limited settings. However, the inability of GART to detect resistance mutations at frequencies Our project aims to determine the discriminatory ability of pre-treatment low frequency HIVDR mutations to predict antiretroviral treatment outcomes. Data and samples (n=1,386) from the REALITY study; a multifactorial trial carried out in 8 sites from 4 sub-Sahara African countries, will be used. Whole genome sequencing (WGS) will be done for all baseline (pre-treatment) samples using a Miseq illumina platform with an established bioinformatics pipeline. The prevalence of pre-treatment low frequency HIVDR variants and their effect on treatment outcomes will be determined. End-points include virologic suppression (viral load, VL 1000 copies/ml at 48 weeks), opportunistic infections (Tuberculosis, Cryptococcus, Candida, severe bacterial infections) and hospital admissions. An attempt will also be made to define cut-off thresholds of clinical significance. Not only will this project build capacity for HIV-1 WGS and assembly, but will also inform HIVDR surveillance policy in sub-Saharan Africa.