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.
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Cunlin
C
Wang
David
D
Vlahov
Noya
N
Galai
Joseph
J
Bareta
Steffanie A
SA
Strathdee
Kenrad E
KE
Nelson
Timothy R
TR
Sterling
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