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Objective: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment.Methods: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100 mg or matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination.Results: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change ϭ 0.12) compared to placebo (mean 24-week change ϭ 0.17) (95% confidence interval ϭ [Ϫ0.26, 0.39], p ϭ 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group.

Background Rifampin is the cornerstone of antituberculosis therapy, but induction of hepatic cytochrome P450 (CYP) 3A by rifampin markedly lowers HIV protease inhibitor plasma concentrations. Methods This phase I, open-label, one-arm study was designed to assess pharmacokinetic interactions and safety of atazanavir, ritonavir, and rifampin among 14 evaluable HIV-seronegative volunteers. The study included three sequential periods of study drug dosing, with plasma sampling for pharmacokinetic analyses to occur on the last day of each period. During period 1, participants received rifampin 600 mg every 24 hours for 8 days. During period 2, participants continued rifampin 600 mg every 24 hours, and added atazanavir 300 mg and ritonavir 100 mg every 12 hours, to continue for at least 11 days. During period 3, atazanavir was to be increased to 400 mg every 12 hours. Results Upon adding atazanavir and ritonavir, the first three subjects developed vomiting and transaminase elevations resulting in study drug discontinuation. The study was therefore terminated. Conclusions Co-administration of rifampin with HIV protease inhibitors may not be a viable treatment option if rifampin administration precedes protease inhibitor initiation. Future studies which explore concomitant HIV protease inhibitors with rifampin must carefully consider the sequence in which drugs are initiated.

The potent induction of hepatic cytochrome P450 3A isoforms by rifampin complicates therapy for coinfection with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis. We performed an open-label, single-arm study to assess the safety and pharmacokinetic interactions of the HIV protease inhibitor atazanavir coadministered with rifampin. Ten healthy HIV-negative subjects completed pharmacokinetic sampling at steady state while receiving 300 mg atazanavir every 12 h without rifampin (period 1), 300 mg atazanavir every 12 h with 600 mg rifampin every 24 h (period 2), and 400 mg atazanavir every 12 h with 600 mg rifampin every 24 h (period 3). During period 1, the mean concentration of drug in serum at 12 h (C(12 h)) was 811 ng/ml (range, 363 to 2,484 ng/ml) for atazanavir, similar to historic seronegative data for once-daily treatment with 300 mg atazanavir boosted with 100 mg ritonavir. During periods 2 and 3, the mean C(12 h) values for atazanavir were 44 ng/ml (range, <25 to 187 ng/ml) and 113 ng/ml (range, 39 to 260 ng/ml), respectively, well below historic seronegative data for once-daily treatment with 400 mg atazanavir without ritonavir. Although safe and generally well tolerated, 300 mg or 400 mg atazanavir administered every 12 h did not maintain adequate plasma exposure when coadministered with rifampin.

Women remain underrepresented in HIV research. The AIDS Clinical Trials Group (ACTG) 5366 study was the first HIV cure-related trial conducted exclusively in women. Our multidisciplinary team integrated participant-centered reports into the ACTG 5366 protocol to elicit their perspectives. We nested mixedmethods surveys at the enrollment and final study visits to assess ACTG 5366 participants' perceptions and experiences. Of 31 participants enrolled in the ACTG 5366, 29 study agreed to complete the entry questionnaire and 27 completed the exit survey. The majority of study participants were nonwhite. We identified societal and personal motivators for participation, understanding of risks and benefits, and minor misconceptions among some trial participants. Stigma was pervasive for several women who joined the study, and served as a motivator for study participation. Reimbursements to defray costs of study participation were reported to facilitate involvement in the trial by about one-third of participants. Almost all respondents reported positive experiences participating in the ACTG 5366 trial. The ACTG 5366 study showed that it is possible to recruit and retain women in HIV cure-related research and to embed participant-centered outcomes at strategic time points during the study. The findings could help in the design, implementation, recruitment, and retention of women in HIV cure-related research and highlight the value of assessing psychosocial factors in HIV cure-related research participation.