Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption

BACKGROUND: Identifying host determinants associated with HIV reservoir size and timing of viral rebound after an analytic treatment interruption (ATI) is an important step in the search for an HIV functional cure. We performed a pooled analysis of 103 participants from 4 AIDS Clinical Trials Group ATI studies to identify the association between HLA class I alleles with HIV reservoir size and viral rebound timing. METHODS: Total HIV DNA and cell-associated HIV RNA (CA-RNA) were quantified in pre-ATI peripheral blood mononuclear cell samples, and residual plasma viremia was measured using the single-copy assay. HLA class I typing was performed, and we generated an odds ratio (OR) of predicted HLA effect on HIV viremia control for each individual and compared this with time to viral rebound, and levels of HIV DNA and CA-RNA. RESULTS: There was no significant association between the HLA ORs and levels of HIV DNA or CA-RNA, but carriage of protective HLA-B alleles (lower OR scores) was associated with delayed viral rebound (P = 0.02). Higher OR scores at the HLA-C locus were associated with longer duration of ART treatment (P = 0.02) and this trend was also seen with the combined OR score (P < 0.01). Individuals with protective HLA-B alleles had delayed viral rebound after treatment interruption that was not explained by differences in baseline reservoir size. CONCLUSIONS: The results indicate the vital role of cellular host immunity in preventing HIV rebound and the importance of taking into account the HLA status of study participants being evaluated in trials for an HIV cure.