The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals.
OBJECTIVE
To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication.


METHODS
A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication.


RESULTS
Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001).


CONCLUSIONS
We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.
Ray
Maile
M
Logan
Roger
R
Sterne
Jonathan A C
JA
Hernández-Díaz
Sonia
S
Robins
James M
JM
Sabin
Caroline
C
Bansi
Loveleen
L
van Sighem
Ard
A
de Wolf
Frank
F
Costagliola
Dominique
D
Lanoy
Emilie
E
Bucher
Heiner C
HC
von Wyl
Viktor
V
Esteve
Anna
A
Casbona
Jordi
J
del Amo
Julia
J
Moreno
Santiago
S
Justice
Amy
A
Goulet
Joseph
J
Lodi
Sara
S
Phillips
Andrew
A
Seng
Rémonie
R
Meyer
Laurence
L
Pérez-Hoyos
Santiago
S
García de Olalla
Patricia
P
Hernán
Miguel A
MA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000401:mortality*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000401:mortality; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D019562:Viral Load