A reduced frequency visit schedule underreports adverse events that resulted in dose modifications or treatment discontinuations in HIV/AIDS clinical trials: ACTG DACS 207

Abstract

Background Most large clinical trials for human immunodeficiency virus (HIV) conducted at university medical centers require intensive real-time monitoring, with clinic visits at least every 4 to 8 weeks. Investigating a reduced frequency visit schedule will help determine whether the current amount of monitoring is needed to ensure subject safety. If we can show that subjects may visit the clinic less often than every 8 weeks and not miss important laboratory-related drug toxicities, then it may be feasible to conduct large studies with simpler designs without compromising the subjects' health. Methods In a retrospective analysis, we examined 3385 study participants who were enrolled in one of four clinical trials conducted by the National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group. Variables examined included age, sex, race, CD4 cell count, HIV antiretroviral use, and medications to treat or prevent selected HIV-associated opportunistic infections. Results Significantly more than the hypothesized 5% of clinic visits with at least one drug toxicity were missed when visits were either every 16 or 24 weeks instead of every 8 weeks (exact Poisson lower 95% confidence bounds = 9.7% and 9.2%, respectively). In both visit-skipping scenarios, there were no significant differences found in the rates of missed drug toxicities by sex or age. However, entry CD4 cell count, HIV antiretroviral use, and medications to treat or prevent two HIV-associated opportunistic infections significantly affected the expected mean number of missed drug toxicities. Conclusion Study visits cannot be extended from every 8 weeks to every 16 or 24 weeks without potentially harming the subjects' health.