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...

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Autores principales: Park, You Jeong, Etemad, Behzad, Ahmed, Hayat, Naranbhai, Vivek, Aga, Evgenia, Bosch, Ronald J., Mellors, John W., Kuritzkes, Daniel R., Para, Michael, Gandhi, Rajesh T., Carrington, Mary, Li, Jonathan Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pathogens and Immunity 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761077/
https://www.ncbi.nlm.nih.gov/pubmed/29333522
http://dx.doi.org/10.20411/pai.v2i3.222
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author Park, You Jeong
Etemad, Behzad
Ahmed, Hayat
Naranbhai, Vivek
Aga, Evgenia
Bosch, Ronald J.
Mellors, John W.
Kuritzkes, Daniel R.
Para, Michael
Gandhi, Rajesh T.
Carrington, Mary
Li, Jonathan Z.
author_facet Park, You Jeong
Etemad, Behzad
Ahmed, Hayat
Naranbhai, Vivek
Aga, Evgenia
Bosch, Ronald J.
Mellors, John W.
Kuritzkes, Daniel R.
Para, Michael
Gandhi, Rajesh T.
Carrington, Mary
Li, Jonathan Z.
author_sort Park, You Jeong
collection PubMed
description 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.
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spelling pubmed-57610772018-01-10 Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption Park, You Jeong Etemad, Behzad Ahmed, Hayat Naranbhai, Vivek Aga, Evgenia Bosch, Ronald J. Mellors, John W. Kuritzkes, Daniel R. Para, Michael Gandhi, Rajesh T. Carrington, Mary Li, Jonathan Z. Pathog Immun Research Article 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. Pathogens and Immunity 2017-11-27 /pmc/articles/PMC5761077/ /pubmed/29333522 http://dx.doi.org/10.20411/pai.v2i3.222 Text en © Pathogens and Immunity 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Article
Park, You Jeong
Etemad, Behzad
Ahmed, Hayat
Naranbhai, Vivek
Aga, Evgenia
Bosch, Ronald J.
Mellors, John W.
Kuritzkes, Daniel R.
Para, Michael
Gandhi, Rajesh T.
Carrington, Mary
Li, Jonathan Z.
Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption
title Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption
title_full Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption
title_fullStr Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption
title_full_unstemmed Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption
title_short Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption
title_sort impact of hla class i alleles on timing of hiv rebound after antiretroviral treatment interruption
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761077/
https://www.ncbi.nlm.nih.gov/pubmed/29333522
http://dx.doi.org/10.20411/pai.v2i3.222
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