Estimating the effect of antiretroviral treatment during HIV seroconversion: impact of confounding in observational data.

OBJECTIVE

To assess whether treatment with antiretroviral drugs within the first 3 months of infection with HIV affects medium-term health outcomes.

DESIGN AND METHODS

Data from 20 cohorts in Europe and Australia were used Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE). Analysis was restricted to persons seroconverting in 1988-1998 who started antiretroviral treatment in the first 3 months or 1-2 years from seroconversion. The relationship between times to low CD4 count, AIDS and death and time of initiation of treatment was estimated using proportional hazards models.

RESULTS

Seroconversion illness was more common in those who began antiretroviral treatment in the first 3 months (73%) than in those who started treatment within 1-2 years post-seroconversion (33%). Subjects receiving early antiretroviral treatment had times to AIDS and to CD4 counts <200 cells/microL that were intermediate between those of subjects starting treatment within 1-2 years and those of the subset of these subjects starting treatment within 1-2 years who also had a prior CD4 count of >350 cells/microL and no prior AIDS diagnosis.

CONCLUSIONS

On the basis of these analyses, the effect of antiretroviral treatment initiation during HIV seroconversion is uncertain. It may result in lower rates of progression compared with starting antiretroviral treatment at 1-2 years, but the early antiretroviral treatment group had a similar or even higher incidence of low CD4 counts and AIDS events than the group who started antiretroviral treatment within 1-2 years with CD4 counts over 350 cells/microL and no prior AIDS diagnosis. Estimates of the effect of early treatment are probably confounded with a number of factors, including, in particular, reasons for treatment initiation.