Phenotypic co-receptor tropism and Maraviroc sensitivity in HIV-1 subtype C from East Africa

Abstract

Abstract Genotypic tropism testing (GTT) for co-receptor usage is a recommended tool for clinical practice before administration of the CCR5-antagonist maraviroc. For some isolates, phenotypic tropism testing (PTT) revealed discordant results with GTT. In this study, we performed a comparative study between GTT and PTT in HIV-1C from East Africa (HIV-1C EA ) and compared the data with HIV-1B and 01_AE and described the maraviroc susceptibility in the CCR5-tropic strains. Patient-derived HIV-1 envgp120 region was cloned into a modified pNL4-3 plasmid expressing the luciferase gene. rPhenotyping dissected single clones from 31 HIV-1C EA infected patients and four strains with known phenotype. Additionally, 68 clones from 18 patients (HIV-1B: 5, 01_AE: 7, HIV-1C EA : 6) were used to determine the PTT in GHOST cell line. The respective V3-sequences were used for GTT. R5-tropic strains from HIV-1C EA (n = 20) and non-C (n = 12) were tested for maraviroc sensitivity in TZMbl cell line. The GTT falsely called a higher proportion of X4-tropic strains in HIV-1C ET compared to PTT by both rPhenotyping and the GHOST-cell assay. When multiple clones were tested in a subset of patients’ samples, both dual-tropic and R5-tropic strains were identified for HIV-1C. Relatively higher EC 50 values were observed in HIV-1C strains than the non-C strains (p = 0.002).