期刊
AIDS
卷 35, 期 5, 页码 783-789出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000002800
关键词
disease progression; HIV-1; human leukocyte antigen; host genetics; immune dysfunction
资金
- National Institutes of Health [U01AI068641, U01AI042170, U01AI046362, UM1AI068641, UM1-AI120197]
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health Clinical Center
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (France)
- National Health and Medical Research Council (Australia)
- National Research Foundation (Denmark)
- Bundes Ministerium fur Bildung und Forschung (Germany)
- European AIDS Treatment Network, Medical Research Council (United Kingdom)
- National Institute for Health Research, National Health Service (United Kingdom)
- University of Minnesota
- Danish National Research Foundation [DNRF126]
The study revealed that certain HLA alleles may influence the risk of clinical events in HIV-positive individuals, irrespective of viral load and CD4(+) T-cell count.
Objectives: The Strategic Timing of AntiRetroviral Treatment (START) and Strategies for Management of Antiretroviral Therapy (SMART) trials demonstrated that ART can partly reverse clinically defined immune dysfunction induced by HIV replication. As control of HIV replication is influenced by the HLA region, we explored whether HLA alleles independently influence the risk of clinical events in HIV+ individuals. Design: Cohort study. Methods: In START and SMART participants, associations between imputed HLA alleles and AIDS, infection-related cancer, herpes virus-related AIDS events, chronic inflammation-related conditions, and bacterial pneumonia were assessed. Cox regression was used to estimate hazard ratios for the risk of events among allele carriers versus noncarriers. Models were adjusted for sex, age, geography, race, time-updated CD4(+) T-cell counts and HIV viral load and stratified by treatment group within trials. HLA class I and II alleles were analyzed separately. The Benjamini--Hochberg procedure was used to limit the false discovery rate to less than 5% (i.e. q value <0.05). Results: Among 4829 participants, there were 132 AIDS events, 136 chronic inflammation-related conditions, 167 bacterial pneumonias, 45 infection-related cancers, and 49 herpes virus-related AIDS events. Several associations with q value less than 0.05 were found: HLA-DQB1*06:04 and HLA-DRB1*13:02 with AIDS (adjusted HR [95% CI] 2.63 [1.5-4.6] and 2.25 [1.4-3.7], respectively), HLA-B*15:17 and HLA-DPB1*15:01 with bacterial pneumonia (4.93 [2.3-10.7] and 4.33 [2.0-9.3], respectively), and HLA-A*69:01 with infection-related cancer (15.26 [3.5-66.7]). The carriage frequencies of these alleles were 10% or less. Conclusion: This hypothesis-generating study suggests that certain HLA alleles may influence the risk of immune dysfunction-related events irrespective of viral load and CD4(+) T-cell count.
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