Mortality in HIV-seropositive versus -seronegative persons in the era of highly active antiretroviral therapy: implications for when to initiate therapy.
BACKGROUND
The optimal time to initiate highly active antiretroviral therapy (HAART) remains unclear.


METHODS
Five hundred eighty-three human immunodeficiency virus (HIV)-seropositive and 920 HIV-seronegative injection drug users (IDUs) were followed from 1997 to 2000. HIV-seropositive participants were categorized according to receipt of HAART (either initiated or switched to HAART) and initial CD4 cell count. Survival analysis that included delayed-entry and Cox proportional-hazards models was used to evaluate the effect of HAART, with adjustments for factors associated with access to HAART.


RESULTS
Compared with HIV-seronegative participants, overall survival was similar in HIV-seropositive participants who received HAART at >350 CD4 cells/microL, but mortality was higher both in participants with >350 CD4 cells/microL who did not receive HAART and in participants who received HAART at 200-350 CD4 cells/microL (mortality rates, 19.9, 24.0, 43.0, and 50.5/1000 person-years, respectively). In proportional-hazards models in which HIV-seronegative participants were the reference group and in which age, sex, race, frequency of drug use, substance-abuse treatment, and health-care utilization were adjusted for, hazard ratios were 1.01 (95% confidence interval [CI], 0.41-2.45), 2.28 (95% CI, 1.38-3.78), and 2.09 (95% CI, 1.07-4.10) for the latter 3 groups. In HIV-seropositive participants, HAART significantly improved survival when initiated at CD4 cell counts < 200 cells/microL.


CONCLUSIONS
Survival of HIV-seropositive participants receiving HAART approximated that of HIV-seronegative participants only when therapy was given at CD4 cell counts > 350 cells/microL. These data, restricted to IDUs, suggest initiating or switching to HAART at higher CD4 cell levels than are currently recommended.
Wang
Cunlin
C
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Vlahov
David
D
Galai
Noya
N
Bareta
Joseph
J
Strathdee
Steffanie A
SA
Nelson
Kenrad E
KE
Sterling
Timothy R
TR
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D018023:HIV Seronegativity; D006679:HIV Seropositivity; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D015819:Substance Abuse, Intravenous / Q000150:complications* / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D019380:Anti-HIV Agents