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

TitleImpact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption.
Publication TypeJournal Article
Year of Publication2017
AuthorsPark YJeong, Etemad B, Ahmed H, Naranbhai V, Aga E, Bosch RJ, Mellors JW, Kuritzkes DR, Para M, Gandhi RT, Carrington M, Li JZ
JournalPathog Immun
Volume2
Issue3
Pagination431-445
Date Published2017
ISSN2469-2964
Abstract

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 (= 0.02). Higher OR scores at the HLA-C locus were associated with longer duration of ART treatment (= 0.02) and this trend was also seen with the combined OR score (< 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.

DOI10.20411/pai.v2i3.222
Alternate JournalPathog Immun
PubMed ID29333522
PubMed Central IDPMC5761077
Grant ListP30 AI060354 / AI / NIAID NIH HHS / United States
R56 AI125109 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States