PMID- 27630231
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20221207
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 22
DP  - 2016 Nov 15
TI  - Dynamics and Correlates of CD8 T-Cell Counts in Africans with Primary Human 
      Immunodeficiency Virus Type 1 Infection.
PG  - 10423-10430
LID - 10.1128/JVI.01467-16 [doi]
AB  - 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. IMPORTANCE: 
      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.
CI  - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved.
FAU - Prentice, Heather A
AU  - Prentice HA
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, 
      USA.
FAU - Lu, Hailin
AU  - Lu H
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, 
      USA.
FAU - Price, Matthew A
AU  - Price MA
AD  - International AIDS Vaccine Initiative, New York, New York, USA.
AD  - Department of Epidemiology and Biostatistics, University of California at San 
      Francisco, San Francisco, California, USA.
FAU - Kamali, Anatoli
AU  - Kamali A
AD  - MRC/UVRI Uganda Virus Research Unit on AIDS, Masaka Site, Masaka, Uganda.
FAU - Karita, Etienne
AU  - Karita E
AD  - Project San Francisco, Kigali, Rwanda.
FAU - Lakhi, Shabir
AU  - Lakhi S
AD  - Zambia-Emory HIV Research Project, Lusaka, Zambia.
FAU - Sanders, Eduard J
AU  - Sanders EJ
AD  - Centre for Geographic Medicine Research, Kenya Medical Research Institute, 
      Kilifi, Kenya.
AD  - Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, 
      Headington, United Kingdom.
FAU - Anzala, Omu
AU  - Anzala O
AD  - Kenya AIDS Vaccine Initiative, Nairobi, Kenya.
FAU - Allen, Susan
AU  - Allen S
AD  - Project San Francisco, Kigali, Rwanda.
AD  - Zambia-Emory HIV Research Project, Lusaka, Zambia.
AD  - Department of Pathology and Laboratory Medicine, Emory University, Atlanta, 
      Georgia, USA.
FAU - Goepfert, Paul A
AU  - Goepfert PA
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, 
      USA.
FAU - Hunter, Eric
AU  - Hunter E
AD  - Vaccine Research Center, Emory University, Atlanta, Georgia, USA.
FAU - Gilmour, Jill
AU  - Gilmour J
AD  - International AIDS Vaccine Initiative, Human Immunology Laboratory, Chelsea and 
      Westminster Hospital, London, United Kingdom.
FAU - Tang, Jianming
AU  - Tang J
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, 
      USA jtang@uab.edu.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - D43 TW001042/TW/FIC NIH HHS/United States
GR  - P51 OD011132/OD/NIH HHS/United States
GR  - R01 AI064060/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20161028
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
SB  - IM
MH  - Adult
MH  - Africa
MH  - Black People
MH  - CD4 Lymphocyte Count/methods
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Female
MH  - Genotype
MH  - HIV Infections/*immunology/*virology
MH  - HIV Seropositivity/immunology
MH  - HIV-1/*immunology
MH  - Humans
MH  - Male
MH  - Viral Load/immunology
PMC - PMC5105675
EDAT- 2016/10/30 06:00
MHDA- 2017/05/10 06:00
PMCR- 2017/04/28
CRDT- 2016/09/16 06:00
PHST- 2016/07/25 00:00 [received]
PHST- 2016/09/07 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2016/09/16 06:00 [entrez]
PHST- 2017/04/28 00:00 [pmc-release]
AID - JVI.01467-16 [pii]
AID - 01467-16 [pii]
AID - 10.1128/JVI.01467-16 [doi]
PST - epublish
SO  - J Virol. 2016 Oct 28;90(22):10423-10430. doi: 10.1128/JVI.01467-16. Print 2016 
      Nov 15.