title: Dynamics and Correlates of CD8 T-Cell Counts in Africans with Primary Human Immunodeficiency Virus Type 1 Infection.
abstract: In individuals with HIV-1 infection, depletion of CD4+T cells is often accompanied by a malfunction of CD8+T cells that are persistently activated and/or exhausted. While the dynamics and correlates of CD4 counts have been well documented, the same does not apply to CD8 counts. Here, we examined the CD8 counts in a cohort of 497 Africans with primary HIV-1 infection evaluated in monthly to quarterly follow-up visits for up to 3 years in the absence of antiretroviral therapy. Statistical models revealed that (i) CD8 counts were relatively steady in the 3- to 36-month period of infection and similar between men and women; (ii) neither geography nor heterogeneity in the HIV-1 set-point viral load could account for the roughly 10-fold range of CD8 counts in the cohort (P > 0.25 in all tests); and (iii) factors independently associated with relatively high CD8 counts included demographics (age ≤ 40 years, adjusted P = 0.010) and several human leukocyte antigen class I (HLA-I) alleles, including HLA-A*03:01 (P = 0.013), B*15:10 (P = 0.007), and B*58:02 (P < 0.001). Multiple sensitivity analyses provided supporting evidence for these novel relationships. Overall, these findings suggest that factors associated with the CD8 count have little overlap with those previously reported for other HIV-1-related outcome measures, including viral load, CD4 count, and CD4/CD8 ratio.
  
  
  OBJECTIVE
  Longitudinal data from 497 HIV-1 seroconverters allowed us to systematically evaluate the dynamics and correlates of CD8+T-cell counts during untreated primary HIV-1 infection in eastern and southern Africans. Our findings suggest that individuals with certain HLA-I alleles, including A*03 (exclusively A*03:01), persistently maintain relatively high CD8 counts following HIV-1 infection, a finding which may offer an intriguing explanation for the recently reported, negative association of A*03 with HIV-1-specific, broadly neutralizing antibody responses. In future studies, attention to HLA-I genotyping data may benefit in-depth understanding of both cellular and humoral immunity, as well as the intrinsic balances of these types of immunity, especially in settings where there is emerging evidence of antagonism between the two arms of adaptive immunity.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Prentice
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Hailin
authors.initials: H
authors.lastname: Lu
authors.affiliation: International AIDS Vaccine Initiative, New York, New York, USA.|Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Price
authors.affiliation: MRC/UVRI Uganda Virus Research Unit on AIDS, Masaka Site, Masaka, Uganda.
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
authors.affiliation: Project San Francisco, Kigali, Rwanda.
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.affiliation: Zambia-Emory HIV Research Project, Lusaka, Zambia.
authors.forename: Shabir
authors.initials: S
authors.lastname: Lakhi
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute, Kilifi, Kenya.|Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Headington, United Kingdom.
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: Project San Francisco, Kigali, Rwanda.|Zambia-Emory HIV Research Project, Lusaka, Zambia.|Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Vaccine Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.affiliation: International AIDS Vaccine Initiative, Human Immunology Laboratory, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA jtang@uab.edu.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
mesh_terms: D000328:Adult; D000349:Africa; D044383:Black People; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D019562:Viral Load / Q000276:immunology