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

作者：Giang Van Tran; Chikata Takayuki; Carlson Jonathan M; Murakoshi Hayato; Dung Hoai Nguyen; Tamura Yoshiko; Akahoshi Tomohiro; Kuse Nozomi; Sakai Keiko; Sakai Sachiko; Cobarrubias Kyle; Oka Shinichi; Brumme Zabrina L; Kinh Van Nguyen; Takiguchi Masafumi

来源：AIDS, 2016, 30(5): 681-689.

DOI：10.1097/QAD.0000000000000969

• human leukocyte antigen-associated polymorphism
• escape mutations
• human leukocyte antigen
• cytotoxic T cells

Objectives:
Identification of human leukocyte antigen-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.
Design:
We investigated HLA-APs in a cohort of chronically HIV-1 subtype A/E-infected Vietnamese individuals.
Methods:
HLA-APs in HIV-1 Gag, Pol, and Nef regions from 388 treatment-naive individuals chronically infected with HIV-1 subtype A/E were analyzed using phylogenetically informed approaches.
Results:
A total of 303 HLA-APs were identified. HLA-APs occurring at six positions in Gag and six positions in Pol were significantly associated with higher plasma viral load (pVL), whereas HLA-APs occurring at two positions in Gag and 13 positions in Pol were significantly associated with lower CD4(+) T-cell 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(+) T-cell counts (R = -0.32; P < 0.0001). Similarly, the proportion of HLA-associated Gag codons harboring host-specific HLA-AP correlated inversely with CD4(+) T-cell counts (R = -0.13; P = 0.01).
Conclusion:
These significant associations between HIV-1 amino acids adapted to Vietnamese HLA alleles and higher pVL and lower CD4(+) T-cell counts suggests that accumulation of cytotoxic T cells escape mutations may influence clinical outcomes in HIV-1 subtype A/E-infected Vietnamese individuals.

• 出版日期2016-3-13