Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV.

TitleRandomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV.
Publication TypeJournal Article
Year of Publication2008
AuthorsCollier AC, Tierney C, Downey GF, Eshleman SH, Kashuba A, Klingman K, Vergis EN, Pakes GE, Rooney JF, Rinehart A, Mellors JW
Corporate AuthorsAIDS Clinical Trials Group Protocol A5143 Team
JournalHIV Clin Trials
Volume9
Issue2
Pagination91-102
Date Published2008 Mar-Apr
ISSN1528-4336
KeywordsAdenine, Adolescent, Adult, Carbamates, Drug Therapy, Combination, Female, HIV Infections, HIV Protease Inhibitors, Humans, Lopinavir, Male, Middle Aged, Organophosphates, Organophosphonates, Pyrimidinones, Ritonavir, RNA, Viral, Sulfonamides, Tenofovir, Viral Load
Abstract

PURPOSE: To compare activity and safety of a regimen containing lopinavir/ritonavir (LPV/r) + fosamprenavir (FPV) to regimens with LPV/r or FPV + r and to test the hypothesis that a ritonavir-enhanced dual protease inhibitor (PI) regimen has better antiviral activity.

METHOD: This study was a multicenter, open-label, randomized study. HIV-infected adults with prior PI failure were selectively randomized based on prior PI experience to either LPV/r, FPV + r, or LPV/r + FPV. All patients received tenofovir DF and 1 to 2 nucleoside reverse transcriptase inhibitors.

RESULTS: Baseline characteristics were similar across arms. Study enrollment and follow-up were stopped early (N = 56) because pharmacokinetic analyses showed significantly lower LPV and FPV exposures in the dual-PI arm. At Week 24, proportions achieving >1 log10 decline in HIV RNA or <50 copies/mL in the dual-PI versus single-PI arms combined were 75% vs. 61% in intent-to-treat (ITT, p = .17) and 100% vs. 64% in as-treated (AT) analyses (p = .02), respectively. Median CD4+ T cell/mm3 increases were 81 vs. 41 (ITT, p = .4) and 114 vs. 43 (AT, p = .08), respectively. Clinical events and toxicity rates were not different between arms.

CONCLUSION: The trial was unable to show a difference between dual versus single PIs in ITT analyses but favored dual PIs in AT analyses.

DOI10.1310/hct0902-91
Alternate JournalHIV Clin Trials
PubMed ID18474494
Grant ListAI 25879 / AI / NIAID NIH HHS / United States
AI025924 / AI / NIAID NIH HHS / United States
AI027665 / AI / NIAID NIH HHS / United States
AI027675 / AI / NIAID NIH HHS / United States
AI046376 / AI / NIAID NIH HHS / United States
AI046383 / AI / NIAID NIH HHS / United States
AI25859 / AI / NIAID NIH HHS / United States
AI25868 / AI / NIAID NIH HHS / United States
AI25897 / AI / NIAID NIH HHS / United States
AI27664 / AI / NIAID NIH HHS / United States
AI27673 / AI / NIAID NIH HHS / United States
AI277664 / AI / NIAID NIH HHS / United States
AI32782 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI463866 / AI / NIAID NIH HHS / United States
P30 AI027757 / AI / NIAID NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States
RR00047 / RR / NCRR NIH HHS / United States
RR000750 / RR / NCRR NIH HHS / United States
RR00096 / RR / NCRR NIH HHS / United States