1. The association of human leukocyte antigen alleles with clinical disease progression in HIV-positive cohorts with varied treatment strategies
- Author
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Cameron Ross MacPherson, Virginia L. Kan, Shweta Sharma, Adrian G. Zucco, Christina Ekenberg, Joanne Reekie, Daniel D Murray, James D. Neaton, Jens D Lundgren, H. Clifford Lane, Abdel Babiker, and Smart Study Groups Insight Start
- Subjects
0301 basic medicine ,Immunology ,HIV Infections ,Human leukocyte antigen ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,HLA Antigens ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Allele ,Alleles ,Proportional hazards model ,Hazard ratio ,Bacterial pneumonia ,medicine.disease ,030104 developmental biology ,Infectious Diseases ,Disease Progression ,HIV-1 ,Viral load ,Cohort study - Abstract
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 (HRs) for the risk of events among allele carriers versus non-carriers. Models were adjusted for sex, age, geography, race, time-updated CD4+ T-cell counts and HIV viral load (VL) 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
- Published
- 2021
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