EVALUATING THE EFFECT OF YEAR OF SEROCONVERSION ON HIV PROGRESSION INCOHORT STUDIES

Objectives: To show how a spurious association between the calendar ye ar of seroconversion and HIV progression arises as a result of censori ng the follow-up of individuals at their last visit, when the individu als' visits are intermittent. Design: A notional cohort of 1140 seroco nverters and a cohort study of 1270 HIV-infected individuals seroconve rted between 1985 and 1994, and followed up to December 1995 (the Ital ian Seroconversion Study cohort). Methods: Failure times and rate of t he patients attending the clinic over the study period were simulated for the notional cohort. Three separate scenarios with different proba bilities of making a visit were considered. Standard survival analysis techniques were used to assess the effect of the year of seroconversi on on HIV progression. The progression to a CD4 cell count of 200 x 10 (6)/l according to the calendar year of seroconversion in the Italian Seroconversion Study was assessed using different censoring strategies . Results: A spurious effect of the year of seroconversion consistentl y appeared in 100 repeated simulations. When ignoring the visits occur ring after the first year of follow-up in the Italian Seroconversion S tudy cohort, results supported the hypothesis of no effect of the year from seroconversion. Conclusions: The choice of the censoring strateg y is crucial when assessing the effect of year of seroconversion using survival analysis in cohort studies with intermittent visit structure . Different censoring strategies should be considered before firmly co ncluding that more virulent strains or the use of treatment are modify ing the natural history of HIV disease from cohort studies of this nat ure. (C) 1998 Lippincott-Raven Publishers.