Changes in the uptake of antiretroviral therapy and survival in people with known duration of HIV infection in Europe: results from CASCADE.

OBJECTIVES: To estimate the times from HIV seroconversion to death, and to the initiation of therapy and the mean CD4 cell count at initiation. DESIGN AND METHODS: Using Kaplan-Meier methods, allowing for late entry, we analysed CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) data from HIV-infected individuals with known dates of seroconversion. We tested the association of time to initiation of therapy and of survival with: exposure category, age, sex, presentation during acute infection and calendar year at risk (as time-dependent) in Cox proportional hazards models, stratifying by study. We estimated the mean CD4 cell count at the initiation of therapy using interval regression. RESULTS: Of 5893 seroconverters, 1613 (27.4%) died. The risk of death was 65% lower (95% CI = 57-72%) in 1997-99 compared to previous years. Being at risk in earlier calendar years, older age and a short interval between negative and positive test dates were associated with shorter survival. At the same time from seroconversion, people at risk in 1997-99, older individuals and people with a short test interval were more likely to initiate therapy. Injecting drug users (IDUs) were less likely to initiate therapy compared to those exposed through sex between men (RR = 0.79, 95% CI = 0.69-0.89). The mean CD4 cell count at therapy initiation was 205 cells/mL, which increased significantly over time. Although the earlier initiation of therapy was consistent with longer survival in the 1997-99 period, we found no evidence of this in other calendar periods. CONCLUSIONS: We found a significant and substantial reduction in the risk of death and a significant trend of earlier initiation of antiretroviral therapy (ART) in the 1997-99 period. Although IDUs were less likely to initiate therapy their overall survival did not appear to differ from others. The increasing tendency to initiate ART closer to seroconversion has unknown long-term consequences which require monitoring