Efficacy and Safety of Twice-Daily versus Three-Times Daily Saquinavir Soft Gelatin Capsules as Part of Triple Combination Therapy for HIV-1 Infection
Authors: Wheat L Joseph , Farthing Charles , Cohen Calvin , Pierone Gerald , Lalezari Jay , Pilson Robert S , Siemon-Hryczyk Peggy ,   for the TIDBID (NR15520/M61018) study team (members listed in Appendix), Baxter John , Beer Victor , Bellos Nicholas C , Bissett Jack , Braun James , Brosgart Carol , Burman William , Burnside Alfred , Cervia Joe , Cheeseman Sarah , Cimoch Paul , Cohen Calvin , DeJesus Edwin , Diaz Leslie , Dieterich Douglas , Dobkin Jay , Dretler Robin , El-Sadr Waafa , Eng Robert , Farthing Charles , Feinberg Judith , Feleke Getachew , Fessel Jeffrey , Fish Douglas , Galpin Jeffrey , Gathe Joseph , Gilson Ian , Gold Marla , Goodgame Jeffrey , Goodrich James , Greenberg Richard , Greiger Paola , Grossman Howard , Grossman Ron , Hanna Barbara , Hathaway Bruce , Hoffman-Terry Margaret , Jacobson Susan , Jemsek Joseph , Jordan Wilbert , Kaplan Mark , Kostman Jay , Lalezari Jacob , Landesman Sheldon , Lindquist Craig , MacArthur Rodger , Madhava Valsa , Marsh Bryan , Martin Dean , Mathur-Wagh Usha , McMeeking Alexander , Miao Peter , Mogyoros Miguel , Murphy Robert , Mustafa Mahmoud , Nadler Jeffrey , Norris Dorece , Onbirbak Brian , Parker Richard H , Pearce Daniel , Pierone Gerald , Poblete Ronald , Poretz Donald M , Reyelt M Christine , Rivera-Vazquez Carlos , Salvato Patricia , Sands Michael , Schwartz Robert , Sension Michael , Skowron Gail , Slater Leonard , Smith David , Stavola Joseph , Steinhart Corklin , Temesgen Zelalem , Thompson Melanie , Timpone Joseph , Valentine Fred T , Vollmer Kelly , Wada Suzanne , Ward Douglas , Wheat L Joseph , Yangco Bienvenido , Carey Peter , Jablonowski Helmut , Theisen Albert , Lazzarin Adriano , Ocana Inma 
Published: April 2022

Objective The objective of this study was to determine whether a triple therapy regimen incorporating twice-daily saquinavir is as effective as a three-times daily regimen. Methods This was an open-label, Phase III, multicentre, 48-week study involving 837 HIV-1-infected patients randomised to one of the following: saquinavir soft gel capsule (SGC) 1200 mg three-times daily, plus two nucleoside reverse transcriptase inhibitors (NRTIs) (arm A); saquinavir SGC 1600 mg twice-daily, plus two NRTIs (arm B); saquinavir SGC 1200 mg twice-daily and nelfinavir 1250 mg twice-daily, plus a single NRTI (arm C). The primary outcome measure was the virological response in arm A versus B and in arm A versus C with respect to the percentage of patients whose plasma HIV-1 RNA levels fell below the level of quantification for the Amplicor assay (<400 copies/ml) at weeks 24 and 48. Results At 48 weeks, the percentage of patients with plasma HIV-1 RNA levels <400 copies/ml was 47.1% (arm A), 45.3% (arm B) and 42.7% (arm C) in the intention-to-treat analysis. The treatment difference between arm B–arm A was -1.8% (95% confidence intervals -10.1, 6.5) and for arm C–arm A was -4.5% (95% confidence intervals -12.7, 3.7) in the intention-to-treat analysis. These differences fell within the maximum allowable difference (±12%) for arm B compared with arm A. At week 24, the percentage of patients with HIV-1 RNA levels <400 copies/ml was 59.6% (arm A), 57.6% (arm B) and 51.3% (arm C). Conclusions A twice-daily triple therapy regimen incorporating saquinavir SGC plus two NRTIs was of equivalent efficacy to the three-times daily regimen studied. All regimens were generally well tolerated.