ABSTRACT
BACKGROUND: Cobicistat (COBI) is a pharmacoenhancer that optimizes systemic exposures of protease inhibitors (PIs) such as atazanavir (ATV) and darunavir (DRV). OBJECTIVE: To evaluate the efficacy and safety of switching ritonavir (RTV) to COBI in patients with creatinine clearance (CrCl) 50 to 89 mL/min who are virologically suppressed on a stable regimen containing ritonavir (RTV)-boosted ATV or DRV. Other components of the regimen remained unchanged. METHODS: A phase 3, non-comparative, open-label clinical trial. RESULTS: Seventy-three patients were enrolled. At week 48, 82% maintained virologic suppression. No emergent resistance developed. Serious adverse events (AEs) occurred in 7%, and study drug discontinuation due to AEs occurred in 10% (7 patients). There were 2 renal discontinuations and no cases of proximal renal tubulopathy. Small reductions in CrCl (median [IQR]) were observed as early as week 2, after which they were nonprogressive through week 48 (-3.8 [-9 to 0.8]). Changes in CrCl by baseline CrCl (< 70 vs ≥ 70) were -1.1 [-6.5 to 6.3] versus -6.6 [-12.4 to -0.7], respectively. CONCLUSIONS: In HIV-1-infected patients with CrCl 50 to 89 mL/min switching from RTV to COBI, COBI-boosted PIs in combination with 2 nucleos(t)ide reverse transcriptase inhibitors were well-tolerated and effective in maintaining virologic suppression. The renal safety profile of COBI in this study was consistent with the long-term data in patients without renal impairment from the phase 3 studies of COBI-containing regimens.
Subject(s)
Carbamates/therapeutic use , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Renal Insufficiency/metabolism , Thiazoles/therapeutic use , Adult , Aged , Carbamates/adverse effects , Carbamates/metabolism , Cobicistat , Female , HIV Infections/complications , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/metabolism , Humans , Male , Middle Aged , Renal Insufficiency/complications , Thiazoles/adverse effects , Thiazoles/metabolismABSTRACT
BACKGROUND: Once daily (QD) dosing facilitates regimen simplification and adherence to antiretroviral therapy. Emtricitabine (FTC) QD is a newly approved nucleoside reverse transcriptase inhibitor compared in this study to twice daily lamivudine (3TC BID). METHODS: Controlled, open label equivalence trial of 440 HIV-1-infected patients with plasma HIV-1 RNA stably suppressed on a regimen of 3TC 150 mg BID, stavudine or zidovudine, and a protease inhibitor or non-nucleoside reverse transcriptase inhibitor. Patients were randomized to continue their current regimen or replace 3TC with FTC 200 mg QD. If HIV-1 RNA levels were = pound 400 copies/ml at 48 weeks in Protocol 303, patients could continue on FTC in Protocol 350. The primary analysis was based on virologic failure and response defined by plasma HIV-1 RNA suppression below 400 copies/ml. RESULTS: At baseline, the mean CD4 cell count was 525 (FTC) and 533 x 10(6) cells/l (3TC). At week 48 in Protocol 303, the probability of virologic failure was low, 7% (FTC) and 8% (3TC), and the probability of sustained viral suppression at week 48 was equivalent between treatment arms at both the 50 and 400 copies/ml thresholds. The mean increase in CD4+ T-cell percentage was 2.5% (FTC) and 1.7% (3TC). In Protocol 350, the probability of virologic failure was 11% after 4 years on FTC-containing highly active antiretroviral therapy (HAART). CONCLUSION: In stably suppressed patients, 200 mg emtricitabine QD was equivalent to 150 mg lamivudine BID. Emtricitabine-containing HAART was associated with a high rate of sustained virologic suppression during 4 years of follow-up.