Impaired protective role of HLA-B*57:01/58:01 in HIV-1 CRF01_AE infection: a cohort study in Vietnam.

ABSTRACT

OBJECTIVES: Human Leukocyte Antigen HLA-B*5701 and B*5801 are considered anti-HIV-1 protective alleles. HLA-B*5701/5801-restricted HIV-1 Gag TW10 (TSTLQEQIGW, Gag residues 240-249) epitope-specific CD8+ T cell responses that frequently select for a Gag escape mutation, T242N, with viral fitness cost are crucial for HIV-1 control. Although this finding has been observed in cohorts where HIV-1 subtype B or C predominates, the protective impact of HLA-B*5701/5801 has not been reported in Southeast Asian countries where HIV-1 CRF01_AE is the major circulating strain. Here, the effect of HLA-B*5701/5801 on CRF01_AE infection was investigated. METHODS: The correlation of HLA-B*5701/5801 with viral load and CD4 counts were analyzed in the CRF01_AE-infected Vietnamese cohort (N = 280). The impact of the T242N mutation on CRF01_AE replication capacity was assessed. RESULTS: HLA-B*5701/5801-positive individuals mostly had HIV-1 with T242N (62/63) but showed neither a significant reduction in viral load nor increased CD4 counts relative to B*5701/5801-negative participants. In vitro and in vivo analyses revealed a significant reduction in viral fitness of CRF01_AE with T242N. In silico analysis indicated reduced presentation of epitopes in the context of CRF01_AE compared to subtype B or C in 10/16 HLA-B*5701/5801-restricted HIV-1 epitopes. CONCLUSION: The protective impact of HLA-B*5701/5801 on CRF01_AE infection is impaired despite strong suppressive pressure by TW10-specific CD8+ T cells.