Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial

• Published in: AIDS research and therapy 2014-12, Vol.11 (1), p.39-39
• Main Authors: Tashima, Karen, Crofoot, Gordon, Tomaka, Frank L, Kakuda, Thomas N, Brochot, Anne, Van de Casteele, Tom, Opsomer, Magda, Garner, William, Margot, Nicolas, Custodio, Joseph M, Fordyce, Marshall W, Szwarcberg, Javier
• Format: Article
• Language: English
• Subjects: Analysis; Antiretroviral drugs; Biological products industry; Diarrhea; Drug dosages; Drug therapy; Drug therapy, Combination; Hepatitis; HIV; HIV (Viruses); Human immunodeficiency virus; Human immunodeficiency virus 1; Infections; Mutation; Patients; Pharmaceuticals; Product development; R&D; Research & development; Studies
• ISSN: 1742-6405; 1742-6405
• DOI: 10.1186/1742-6405-11-39

Cobicistat is an alternative pharmacoenhancer to ritonavir. In healthy volunteers, darunavir exposure was comparable when darunavir 800 mg once daily was co-administered with cobicistat 150 mg once daily (as single agents or a fixed-dose combination) vs. with ritonavir 100 mg once daily. This 48-week, Phase IIIb, single-arm, US multicenter study (NCT01440569) evaluated safety, efficacy and pharmacokinetics of darunavir/cobicistat 800/150 mg once daily (as single agents) plus two investigator-selected nucleoside/tide reverse transcriptase inhibitors (N[t]RTIs) in HIV-1-infected adults. Patients had no darunavir resistance-associated mutations (RAMs), plasma viral load (VL) ≥1000 HIV-1 RNA copies/ml, eGFR ≥80 ml/min and genotypic sensitivity to the two N[t]RTIs. The primary endpoint was any treatment-emergent grade 3 or 4 adverse events (AEs) through Week 24. The majority of the 313 intent-to-treat patients were treatment-naïve (295/313; 94%), male (89%), White (60%) and received a tenofovir-based regimen (99%). Median baseline VL and CD4(+) count overall were 4.8 log10 HIV-1 RNA copies/ml and 361 cells/mm(3), respectively. Overall, 86% of patients (268/313) completed the study. The majority of discontinuations were for AEs (15/313; 5%). The incidence of treatment-emergent grade 3 or 4 AEs regardless of causality was 6% through Week 24 and 8% through Week 48. Most common AEs through Week 48 were diarrhea (27%) and nausea (23%), which were grade 1 or 2 in severity. Week 48 virologic response rates (% with VL