St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
BACKGROUND: The safety of delaying highly active antiretroviral therapy (HAART) in HIV-infected patients is uncertain when the CD4+ cell count declines below 0.350 x 10(9) cells/L. OBJECTIVE: To evaluate the effect of baseline CD4+ cell count and adherence to HAART on survival rates. DESIGN: Prospective observational study. SETTING: Province-wide Canadian HIV/AIDS treatment program. PATIENTS: 1422 HIV-infected persons initiating HAART between 1 August 1996 and 31 July 2000 and followed through 31 March 2002. MEASUREMENTS: Patients were stratified by baseline CD4+ cell count and adherence level. Cumulative mortality rates were evaluated by using Kaplan-Meier methods and Cox regression-estimated adjusted relative hazards. RESULTS: Kaplan-Meier analyses showed no survival benefit of starting HAART at a CD4+ count of 0.200 x 10(9) cells/L or greater among adherent patients. Adjusted analysis showed that compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, nonadherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically elevated mortality rates (adjusted relative hazard, 2.56 [95% CI, 1.36 to 4.84]; P = 0.004). However, compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, adherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically similar mortality rates (adjusted relative hazard, 0.82 [CI, 0.45 to 1.49]; P > 0.2). CONCLUSIONS: Delaying HAART until the CD4+ cell count falls to 0.200 x 109 cells/L does not increase the mortality rate in HIV-infected patients with good medication adherence. Mortality rates increase if HAART is initiated below 0.200 x 10(9) cells/L. Also, nonadherent patients have higher mortality rates than adherent patients with similar CD4+ cell counts. Above a CD4+ cell count of 0.200 x 10(9) cells/L, medication adherence is the critical determinant of survival, not the CD4+ cell count at which HAART is begun.