Incidence rate of and factors associated with loss to follow-up in a longitudinal cohort of antiretroviral-treated HIV-infected persons: an AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) analysis.

PURPOSE: Examine incidence and factors associated with loss to follow-up (LTFU) in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort. METHOD: ALLRT is a prospective cohort of HIV-infected persons randomized to antiretroviral (ARV) regimens/strategies in ACTG trials and followed long-term after the trial ends. Person-years were calculated from ALLRT entry until loss to follow-up (LTFU; defined using off-study reasons or ≥ 3 consecutive missed visits), death/ severe debilitation/site closures, or June 2009 (censored). Poisson regression was used to examine LTFU factors separately among participants who were ARV naïve or ARV experienced at trial entry. RESULTS: Among 4,630 participants (22,524 person-years), 1,140 were lost to follow-up, 237 died, 29 were severely debilitated, and 443 were at sites that closed. The LTFU incidence was 5.5 and 4.2 per 100 person-years among previously ARV-naïve and ARV-experienced participants, respectively. In both groups, age ≤ 50, site location, being off ARVs, and viral load ≥ 400 copies/mL were associated with a higher risk of LTFU. Among ARV-naïve participants, male sex, education <16 years, intravenous drug use, and cigarette smoking were also associated with LTFU. CONCLUSION: Knowledge of differential LTFU can help researchers identify participants at risk of LTFU in longitudinal HIV cohorts and design retention strategies, thereby limiting study bias. The identified factors should be included in inverse probability of weighting models to account for LTFU.

Virologic responses to a ritonavir--saquinavir-containing regimen in patients who had previously failed nelfinavir.

OBJECTIVES: The effectiveness of a second protease inhibitor in patients who failed an initial protease inhibitor is unclear but believed to be low. It has been postulated, however, that patients who fail nelfinavir may respond differently. We therefore assessed the virologic response to a ritonavir-saquinavir-containing regimen in patients who had previously failed nelfinavir. METHODS: A total of 26 patients enrolled in the nelfinavir clinical trials AG506 and AG511 at our two sites who failed (two consecutive HIV viral loads > 5000 copies/ml; branched DNA assay) were switched to a combination of stavudine 40 mg twice daily, lamivudine 150 mg twice daily, ritonavir 400 mg twice daily and saquinavir 400 mg twice daily. RESULTS: The mean viral load at enrollment in this study was 46 674 copies/ml (range, 1075-146400 copies/ml). The median CD4 cell count was 222 x 10(6)/l (range, 82-448 x 10(6)/l). The median duration of nelfinavir use with a detectable viral load before the switch occurred was 48 weeks. Two patients discontinued the study at 3 weeks. All of the remaining patients (n = 24) reached undetectable viral loads (< 500 copies/ml) that were sustained at week 24 in 17 (71%) out of 24 subjects. The most frequent baseline mutations in the protease gene prior to switching were D30N (13 out of 18), N88D (eight out of 18) and M36I (eight out of 18). The presence or absence of these mutations was not predictive of a short-term virologic response. CONCLUSIONS: Most patients who failed a nelfinavir-containing regimen responded to a switch to a combination regimen with saquinavir-ritonavir.