Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies.
BACKGROUND
Insufficient data are available from single cohort studies to allow estimation of the prognosis of HIV-1 infected, treatment-naive patients who start highly active antiretroviral therapy (HAART). The ART Cohort Collaboration, which includes 13 cohort studies from Europe and North America, was established to fill this knowledge gap.


METHODS
We analysed data on 12,574 adult patients starting HAART with a combination of at least three drugs. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. We considered progression to a combined endpoint of a new AIDS-defining disease or death, and to death alone. The prognostic model that generalised best was a Weibull model, stratified by baseline CD4 cell count and transmission group. FINDINGS During 24,310 person-years of follow up, 1094 patients developed AIDS or died and 344 patients died. Baseline CD4 cell count was strongly associated with the probability of progression to AIDS or death: compared with patients starting HAART with less than 50 CD4 cells/microL, adjusted hazard ratios were 0.74 (95% CI 0.62-0.89) for 50-99 cells/microL, 0.52 (0.44-0.63) for 100-199 cells/microL, 0.24 (0.20-0.30) for 200-349 cells/microL, and 0.18 (0.14-0.22) for 350 or more CD4 cells/microL. Baseline HIV-1 viral load was associated with a higher probability of progression only if 100,000 copies/microL or above. Other independent predictors of poorer outcome were advanced age, infection through injection-drug use, and a previous diagnosis of AIDS. The probability of progression to AIDS or death at 3 years ranged from 3.4% (2.8-4.1) in patients in the lowest-risk stratum for each prognostic variable, to 50% (43-58) in patients in the highest-risk strata.


CONCLUSIONS
The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART. Our findings have important implications for clinical management and should be taken into account in future treatment guidelines.
Department of Social and Preventive Medicine, University of Bern, CH-3012 Bern, Switzerland. egger@ispm.unibe.ch
Matthias
M
Egger
Margaret
M
May
Geneviève
G
Chêne
Andrew N
AN
Phillips
Bruno
B
Ledergerber
François
F
Dabis
Dominique
D
Costagliola
Antonella
A
D'Arminio Monforte
Frank
F
de Wolf
Peter
P
Reiss
Jens D
JD
Lundgren
Amy C
AC
Justice
Schlomo
S
Staszewski
Catherine
C
Leport
Robert S
RS
Hogg
Caroline A
CA
Sabin
M John
MJ
Gill
Bernd
B
Salzberger
Jonathan A C
JA
Sterne
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014481:United States; D019562:Viral Load