Evaluation of C-terminal p7 (NC)-p6 Gag genetic variants among HIV-1 non-B subtypes in a subset of Cameroonian patients

Abstract

Response to ritonavir-boosted-protease inhibitors (PI/r)-based regimen is associated with some Gag mutations among HIV-1 B-clade. There is limited data on Gag variants and their covariation with mutations in protease among HIV-1 non-B-clades at PI/r-based treatment failure. Thus, we characterized Gag variants present in isolates from HIV-1 infected individuals treated to a PI/r-regimen (n=143) and compared them to those obtained from individuals not treated to PI/r (ART-naïve [n=101] or RTI-treated [n=118]). The most frequent HIV-1 subtypes were CRF02_AG (54.69%), A (13.53%), D (6.35%) and G (4.69%). Eighteen Gag variants (distributed in three groups) showed a significantly higher prevalence in PI/r-treated isolates compared to ART-naïve (p<0.05): Group 1 (prevalence <1% in drug-naïve): L449F, D480N, L483Q, Y484P, T487V; group 2 (prevalence 1%-5% in drug-naïve): S462L, I479G, I479K, D480E; group 3 (prevalence ≥5% in drug-naïve): P453L, E460A, R464G, S465F, V467E, Q474P, I479R, E482G, T487A. Five Gag variants (L449F, P453L, D480E, S465F, Y484P) positively correlated (Phi ≥0.2, p<0.05) with protease-resistance mutations. At PI/r-failure, no significant difference was observed between patients with and without these associated Gag variants in term of viremia or CD4 count. This analysis suggests that some Gag variants are significantly associated with an increased frequency at PI/r failure among HIV-1 non-B clades.