Early Initiation Rather Than Prolonged Duration of Antiretroviral Therapy in HIV Infection Contributes to the Normalization of CD8 T-Cell Counts.
BACKGROUND
CD8 T-cell counts remain elevated in human immunodeficiency virus (HIV) infection even after long-term antiretroviral therapy (ART), which is associated with an increased risk of non-AIDS-related events. We assessed the impact of ART initiation in early versus chronic HIV infection on trajectories of CD8 cell counts over time.


METHODS
Of 280 individuals enrolled during primary HIV infection (PHI), 251 were followed up for 24 months; 84 started ART before 6 months of infection (eART), 49 started between 6 and 24 months, and 118 remained untreated. Plasma HIV viral load (VL), CD4 and CD8 cell counts were assessed at each study visit. CD8 counts were also examined in 182 age-matched HIV-infected individuals who started ART during chronic infection and maintained undetectable plasma VL for ≥5 years.


RESULTS
At PHI baseline, higher CD8 cell counts were associated with more recent infection (P = .02), higher CD4 cell counts (P < .001), and higher VL (P < .001). The CD8 count in the eART group decreased from 797 to 588 cells/µL over 24 months (P < .001), to a level lower than that in untreated PHI (834 cells/µL; P = .004) or in long-term-treated patients with chronic HIV infection (743 cells/µL; P = .047). More prominent CD4 T-cell recovery was observed in the eART group than in the delayed ART group.


CONCLUSIONS
ART initiated in early HIV infection is associated with improved resolution of CD8 T-cell elevation compared with long-term ART initiated in chronic infection. Early ART may help reduce the risk of non-AIDS-related events by alleviating this elevation.
Research Institute of the McGill University Health Centre.|Chronic Viral Illness Service.|Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China.
Wei
W
Cao
Research Institute of the McGill University Health Centre.|Chronic Viral Illness Service.
Vikram
V
Mehraj
Clinique Médicale l'Actuel.
Benoit
B
Trottier
Clinique Médicale Quartier Latin.
Jean-Guy
JG
Baril
Chronic Viral Illness Service.|Clinique Médicale OPUS.
Roger
R
Leblanc
Chronic Viral Illness Service.
Bertrand
B
Lebouche
Chronic Viral Illness Service.
Joseph
J
Cox
CHUM Research Centre.|Department of Microbiology and Immunology, University of Montreal, Quebec, Canada.
Cecile
C
Tremblay
Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China.
Wei
W
Lu
School of Population and Public Health, University of British Columbia, Vancouver, Canada.
Joel
J
Singer
Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China.
Taisheng
T
Li
Research Institute of the McGill University Health Centre.|Chronic Viral Illness Service.|Division of Hematology, McGill University Health Centre.
Jean-Pierre
JP
Routy
S
S
Vézina
L
L
Charest
M
M
Milne
E
E
Huchet
S
S
Lavoie
J
J
Friedman
M
M
Duchastel
F
F
Villielm
P
P
Côté
M
M
Potter
B
B
Lessard
M A
MA
Charron
S
S
Dufresne
M E
ME
Turgeon
D
D
Rouleau
L
L
Labrecque
C
C
Fortin
A
A
de Pokomandy
V
V
Hal-Gagné
M
M
Munoz
B
B
Deligne
V
V
Martel-Laferrière
N
N
Gilmore
M
M
Fletcher
J
J
Szabo
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D055502:Secondary Prevention; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents; D012367:RNA, Viral
CD4/CD8 ratio; CD8 T-cell count; HIV; antiretroviral therapy; primary infection