PMID- 30629187
OWN - NLM
STAT- MEDLINE
DCOM- 20200302
LR  - 20240306
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 219
IP  - 12
DP  - 2019 May 24
TI  - HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the 
      Proportion of PD-1-Expressing CD8+ T Cells and Reverses With Antiretroviral 
      Therapy.
PG  - 1948-1958
LID - 10.1093/infdis/jiz015 [doi]
AB  - BACKGROUND: The contribution of immune activation to arterial stiffness and its 
      reversibility in human immunodeficiency virus (HIV)-infected adults in 
      sub-Saharan Africa is unknown. METHODS: HIV-uninfected and HIV-infected Malawian 
      adults initiating antiretroviral therapy (ART) with a CD4+ T-cell count of <100 
      cells/muL were enrolled and followed for 44 weeks; enrollment of infected adults 
      occurred 2 weeks after ART initiation. We evaluated the relationship between 
      carotid femoral pulse wave velocity (cfPWV) and T-cell activation (defined as 
      HLA-DR+CD38+ T cells), exhaustion (define as PD-1+ T cells), and senescence 
      (defined as CD57+ T cells) and monocyte subsets, using normal regression. 
      RESULTS: In 279 HIV-infected and 110 HIV-uninfected adults, 142 (37%) had 
      hypertension. HIV was independently associated with a 12% higher cfPWV (P = .02) 
      at baseline and a 14% higher cfPWV at week 10 (P = .02), but the increases 
      resolved by week 22. CD4+ and CD8+ T-cell exhaustion were independently 
      associated with a higher cfPWV at baseline (P = .02). At 44 weeks, arterial 
      stiffness improved more in those with greater decreases in the percentage of CD8+ 
      T cells and the percentage of PD-1+CD8+ T cells (P = .01 and P = .03, 
      respectively). When considering HIV-infected participants alone, the adjusted 
      arterial stiffness at week 44 tended to be lower in those with higher baseline 
      percentage of PD-1+CD8+ T cells (P = .054). CONCLUSIONS: PD-1+CD8+ T-cells are 
      associated with HIV-related arterial stiffness, which remains elevated during the 
      first 3 months of ART. Resources to prevent cardiovascular disease in sub-Saharan 
      Africa should focus on blood pressure reduction and individuals with a low CD4+ 
      T-cell count during early ART.
CI  - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Kelly, Christine
AU  - Kelly C
AD  - Insitute of Translational Medicine, University of Liverpool.
AD  - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine.
AD  - HIV Molecular Research Group, University College Dublin, Ireland.
FAU - Mwandumba, Henry C
AU  - Mwandumba HC
AD  - Department of Clinical Sciences, Liverpool School of Tropical Medicine, 
      Liverpool.
AD  - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine.
AD  - Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi.
FAU - Heyderman, Robert S
AU  - Heyderman RS
AD  - Division of Infection and Immunity.
AD  - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine.
FAU - Jambo, Kondwani
AU  - Jambo K
AD  - Department of Clinical Sciences, Liverpool School of Tropical Medicine, 
      Liverpool.
AD  - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine.
FAU - Kamng'ona, Raphael
AU  - Kamng'ona R
AD  - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine.
FAU - Chammudzi, Mishek
AU  - Chammudzi M
AD  - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine.
FAU - Sheha, Irene
AU  - Sheha I
AD  - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine.
FAU - Peterson, Ingrid
AU  - Peterson I
AD  - Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine.
FAU - Rapala, Alicja
AU  - Rapala A
AD  - Institute for Cardiovascular Sciences.
FAU - Mallewa, Jane
AU  - Mallewa J
AD  - Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi.
FAU - Walker, A Sarah
AU  - Walker AS
AD  - MRC Clinical Trials Unit.
FAU - Klein, Nigel
AU  - Klein N
AD  - Institute of Child Health, University College London, London, United Kingdom.
FAU - Khoo, Saye
AU  - Khoo S
AD  - Insitute of Translational Medicine, University of Liverpool.
LA  - eng
GR  - MC_EX_G1100693/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_12023/23/MRC_/Medical Research Council/United Kingdom
GR  - MC_EX_UU_G1100693/MRC_/Medical Research Council/United Kingdom
GR  - MR/P020526/1/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_12023/26/MRC_/Medical Research Council/United Kingdom
GR  - 099934/Z/12/A/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Adult
MH  - Anti-Retroviral Agents/pharmacology/*therapeutic use
MH  - CD8-Positive T-Lymphocytes/cytology/*metabolism
MH  - *HIV Infections/drug therapy/physiopathology
MH  - Humans
MH  - Malawi
MH  - Male
MH  - Programmed Cell Death 1 Receptor/*metabolism
MH  - Vascular Stiffness/*drug effects
PMC - PMC6534190
OTO - NOTNLM
OT  - HIV
OT  - PD-1
OT  - T-cell exhaustion
OT  - arterial stiffness
OT  - cardiovascular disease
OT  - endothelial damage
OT  - sub-Saharan Africa
EDAT- 2019/01/11 06:00
MHDA- 2020/03/03 06:00
PMCR- 2019/01/09
CRDT- 2019/01/11 06:00
PHST- 2018/10/07 00:00 [received]
PHST- 2019/01/08 00:00 [accepted]
PHST- 2019/01/11 06:00 [pubmed]
PHST- 2020/03/03 06:00 [medline]
PHST- 2019/01/11 06:00 [entrez]
PHST- 2019/01/09 00:00 [pmc-release]
AID - 5283190 [pii]
AID - jiz015 [pii]
AID - 10.1093/infdis/jiz015 [doi]
PST - ppublish
SO  - J Infect Dis. 2019 May 24;219(12):1948-1958. doi: 10.1093/infdis/jiz015.