Evaluation of multiple failure time analyses of observational data in patients treated for HIV

The development of protease inhibitors and nonnucleoside reverse transcriptase inhibitors has substantially increased the number of combinations available for multi-drug therapies in human immunodeficiency virus (HIV) infection. Unfortunately, all antiretroviral therapies lose efficacy over time or induce side effects, thus making secondary and tertiary alternatives necessary. With the multiplicity of multi-drug combination therapies, the challenge is to determine which multi-drug combination to use as initial therapy and which to use as subsequent therapy to maximize survival. No standard methodologic approach has been developed to answer this question within the context of observational clinical HIV data. We demonstrate the use of semi-parametric models employing repeated, multiple failure time analysis to compare the relative efficacy of treatments containing zidovudine, stavudine, or other multi-drug combinations for patients in the CHORUS (Collaborations in HIV Outcomes Research - US) database.