PREDICTORS AND IMPACT OF PATIENTS LOST TO FOLLOW-UP IN A LONG-TERM RANDOMIZED TRIAL OF IMMEDIATE VERSUS DEFERRED ANTIRETROVIRAL TREATMENT

We studied predictors for losses to follow-up and the impact of such l osses in the AIDS Clinical Trials Group 019 protocol, a long-term rand omized trial of immediate versus deferred antiretroviral therapy in as ymptomatic HIV-l-infected patients with > 500 CD4 cells/mm(3). The tri al was selected because of its key importance in determining guideline s for antiretroviral therapy, and because it had the longest follow-up among all antiretroviral trials and the largest percentage of patient s whose vital status was unknown at study end. Younger age, a history of parenteral drug use, and nonwhite race were associated with higher rates of loss to follow-up, but race was not an important predictor af ter adjusting for clinical site. There was large and statistically sig nificant variability in the rates of losses among different clinical s ites (P < 0.001). Patient retention was significantly better in clinic al sites that enrolled many participants, with 25% of enrollees lost t o follow-up in sites enrolling > 100 patients and 44% in sites enrolli ng < 33 patients each. As a group, patients lost to follow-up after th e 2nd year had steeper declines of CD4 cell counts, and a significantl y larger proportion had reached a CD4 cell count < 300/mm(3) in the ye ar before being lost, compared with patients remaining in the study. L osses to follow-up probably decreased substantially the observed numbe r of primary endpoints, curtailed the power of the trial to demonstrat e any difference between immediate and deferred initiation of antiretr oviral therapy, and may have introduced large bias in the estimated ha zard ratio for the primary endpoint and its statistical significance.