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


  • CASCADE Collaboration

  • Correspondence: K Porter, MRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA. Tel: +44-20-7670-4715. Fax: +44-20-7670-4818.



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.