A strong association of HLA-associated Pol and Gag mutations with clinical parameters in HIV-1 subtype A/E infection

April 14 2016

Masafumi Takiguchi

Paper information

Tran GV, * Chikata T,* Carson J M., Murakoshi H, Nguyen D H, Tamura Y, Akahoshi T, Kuse N, Sakai K, Sakai S, Cobarrubias K, Oka S, Brumme Z L., Nguyen K V, and Takiguchi M; (* equal contribution) A strong association of HLA-associated Pol and Gag mutations with clinical parameters in HIV-1 subtype A/E infection, AIDS 30:681-689, 2016

Highlights

We identified 303 HLA-associated polymorphisms (HLA-APs) in 388 treatment-naïve chronically HIV-1 subtype A/E-infected Vietnamese individuals. 

The number of HLA-APs and the proportion of escape mutations in Pol correlated positively with pVL and inversely with CD4 counts.

Several HLA-APs occurring in Gag and Pol were significantly associated with clinical markers in HIV-1 subtype A/E-infection.

Abstract

Identification of HLA-associated HIV-1 polymorphisms (HLA-APs) in different global populations furthers our understanding of HIV-1 pathogenesis and may help identify candidate immunogens for HIV vaccines targeted to these populations. Although numerous population-based studies identifying HLA-APs have been conducted in HIV-1 subtype B- and subtype C-infected cohorts, few have focused on subtype A/E which is epidemic in South-East Asia.

We investigated HLA-APs in a cohort of chronically HIV-1 subtype A/E-infected Vietnamese individuals in Hanoi. HLA-APs in HIV-1 Gag, Pol, and Nef regions from 388 treatment-naïve individuals chronically infected with HIV-1 subtype A/E were analyzed using phylogenetically-informed approaches. A total of 303 HLA-APs were identified. HLA-APs occurring at 6 positions in Gag and 6 positions in Pol were significantly associated with higher pVL, whereas HLA-APs occurring at 2 positions in Gag and 13 positions in Pol were significantly associated with lower CD4 counts. Furthermore, the proportion of Pol codons harboring an HLA-AP specific to the host's HLA correlated positively with HIV-1 pVL (R = 0.22; p<0.0001) and inversely with CD4 counts (R = -0.32; p<0.0001). Similarly, the proportion of HLA-associated Gag codons harboring host-specific HLA-AP correlated inversely with CD4 counts (R = -0.13; p = 0.01).

These significant associations between HIV-1 amino acids adapted to Vietnamese HLA alleles and higher pVL and lower CD4 counts suggests that accumulation of CTL escape mutations may influence clinical outcomes in HIV-1 subtype A/E-infected Vietnamese individuals.