Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection

Viral mutations at Gag residue 242 and relevant viral polymorphisms were analyzed in a cohort of 42 individuals with primary HIV-1 subtype C infection using single-genome amplification/sequencing. In HLA-B57/5801-negative subjects infected with 242N escape variant, reversion to Asn appeared at median (IQR) 103. days (97-213. days) post-seroconversion (p/s) and became dominant at 193. days (170-215. days) p/s. In subjects expressing HLA-B57/5801 and infected with the wild-type virus, the T242N escape appeared at 203. days (196-231) p/s, reached dominance at 277. days (265-315. days) p/s, and became complete at 323. days (289-373. days) p/s. HLA-B57/5801-negative subjects infected with 242N escape variant did not show reduced viral load or increased CD4 count. The study highlights the differential selection of T242N escape by HLA-B57 and B5801 and suggests that the presence of HLA-B57/5801-mediated immune pressure is able to control replication of the wild-type virus encoding Thr at Gag residue 242 but fails to suppress the T242N escape variant. © 2010 Elsevier Inc.