How soon after HIV seroconversion is antiretroviral therapy initiated?

Objective: To estimate the time from HIV seroconversion to initiating antiretroviral therapy (ART) and whether this has changed over calendar time, and to estimate the CD4 cell count at which ART is initiated. Design: Data from a cohort of HIV seroconverters in the UK were analysed with the initiation of ART as the outcome variable. Method: The association of the time from seroconversion to initiating ART with age, sex, exposure category, calendar time, CD4 cell count and acute infection at diagnosis was examined using Kaplan-Meier plots and Cox proportional hazards models. The CD4 level at which therapy was initiated was examined. Results Of 1308 seroconverters, 710 (54%) had started ART by 30 September 1998. Median interval from seroconversion to initiating ART was estimated to be 59.5 months [95% confidence interval (CI), 54.7-63.6]. Compared with 1989-1994 (after adjusting for CD4 cell count), time to initiation of ART was significantly shorter in 1997-1998 with relative rates of initiating ART of 1.02 (95% CI, 0.67-1.55), 1.07 (95% CI, 0.88-1.31) and 3.16 (95% CI, 2.56-3.90) pre-1989, 1995-1996, and 1997-1998, respectively. Median CD4 cell count at initiation of treatment was 73 (95% CI, 30-109), 136 (95% CI, 118-161), 110 (95% CI, 84-140) and 221 (35% CI, 200-250) x 10(6) cells/l for the periods pre-1989, 1989-1994, 1995-1996 and 1997-1998, respectively. Of persons seroconverting in 1997-1998, 19.5% initiated ART within 6 months of seroconversion compared with 8.4% and 2.0% in 1995-1996 and 1989-1994, respectively. Conclusions: ART is being initiated closer to HIV seroconversion than in previous years. Whether the improvements in survival reported from recent observational studies result solely from increased efficacy of the regimens or also from the timing of their initiation is difficult to determine. No clinical trial has yet addressed the optimum timing of initiating ART in the era of potent therapies. (C) 1999 Lippincott Williams & Wilkins.