Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery.
BACKGROUND
Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality.


METHODS
We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality.


RESULTS
Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death.


CONCLUSIONS
Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.
Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital.
Frederik N
FN
Engsig
Robert
R
Zangerle
Olga
O
Katsarou
Francois
F
Dabis
Peter
P
Reiss
John
J
Gill
Kholoud
K
Porter
Caroline
C
Sabin
Andrew
A
Riordan
Gerd
G
Fätkenheuer
Félix
F
Gutiérrez
Francois
F
Raffi
Ole
O
Kirk
Murielle
M
Mary-Krause
Christoph
C
Stephan
Patricia Garcia
PG
de Olalla
Jodie
J
Guest
Hasina
H
Samji
Antonella
A
Castagna
Antonella
A
d'Arminio Monforte
Adriane
A
Skaletz-Rorowski
Jose
J
Ramos
Giuseppe
G
Lapadula
Cristina
C
Mussini
Lluís
L
Force
Laurence
L
Meyer
Fiona
F
Lampe
Faroudy
F
Boufassa
Heiner C
HC
Bucher
Stéphane
S
De Wit
Greer A
GA
Burkholder
Ramon
R
Teira
Amy C
AC
Justice
Tim R
TR
Sterling
Heidi
H
M Crane
Jan
J
Gerstoft
Jesper
J
Grarup
Margaret
M
May
Geneviève
G
Chêne
Suzanne M
SM
Ingle
Jonathan
J
Sterne
Niels
N
Obel
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality* / Q000635:transmission; D020010:Heterosexuality; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000150:complications; D019562:Viral Load
D019380:Anti-HIV Agents
CD4 cell recovery; HIV; mortality; risk factors; sustained viral suppression