title: CD4:CD8 lymphocyte ratio as a quantitative measure of immunologic health in HIV-1 infection: findings from an African cohort with prospective data.
abstract: In individuals with human immunodeficiency virus type 1 (HIV-1) infection, CD4:CD8 lymphocyte ratio is often recognized as a quantitative outcome that reflects the critical role of both CD4(+) and CD8(+) T-cells in HIV-1 pathogenesis or disease progression. Our work aimed to first establish the dynamics and clinical relevance of CD4:CD8 ratio in a cohort of native Africans and then to examine its association with viral and host factors, including: (i) length of infection, (ii) demographics, (iii) HIV-1 viral load (VL), (iv) change in CD4(+) T-lymphocyte count (CD4 slope), (v) HIV-1 subtype, and (vi) host genetics, especially human leukocyte antigen (HLA) variants. Data from 499 HIV-1 seroconverters with frequent (monthly to quarterly) follow-up revealed that CD4:CD8 ratio was stable in the first 3 years of infection, with a modest correlation with VL and CD4 slope. A relatively normal CD4:CD8 ratio (>1.0) in early infection was associated with a substantial delay in disease progression to severe immunodeficiency (<350 CD4 cells/μl), regardless of other correlates of HIV-1 pathogenesis (adjusted hazards ratio (HR) = 0.43, 95% confidence interval (CI) = 0.29-0.63, P < 0.0001). Low VL (<10,000 copies/ml) and HLA-A*74:01 were the main predictors of CD4:CD8 ratio >1.0, but HLA variants (e.g., HLA-B*57 and HLA-B*81) previously associated with VL and/or CD4 trajectories in eastern and southern Africans had no obvious impact on CD4:CD8 ratio. Collectively, these findings suggest that CD4:CD8 ratio is a robust measure of immunologic health with both clinical and epidemiological implications.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL USA.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Li
authors.affiliation: International AIDS Vaccine Initiative, New York, NY USA ; Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Price
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute, Kilifi Kenya ; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford UK.
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Sanders
authors.affiliation: Kenya AIDS Vaccine Initiative, Nairobi Kenya.
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.affiliation: Projet San Francisco, Kigali Rwanda.
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.affiliation: Uganda Virus Research Unit on AIDS, Medical Research Council/Uganda Virus Research Institute, Masaka Uganda.
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
authors.affiliation: Zambia-Emory HIV Research Project, Lusaka Zambia.
authors.forename: Shabir
authors.initials: S
authors.lastname: Lakhi
authors.affiliation: Zambia-Emory HIV Research Project, Lusaka Zambia ; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, GA USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.affiliation: International AIDS Vaccine Initiative, Human Immunology Laboratory, Chelsea and Westminster Hospital, London UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
keywords: Africa; CD4:CD8 ratio; HIV-1; HLA; statistical models; subtype; viral load