A Study of Several Anti-HIV Drug Combinations in HIV-Infected Patients Who Have Used Indinavir

Summary

To compare the proportion of patients whose plasma HIV-1 RNA is below 500 copies/ml after 16 weeks of treatment. To assess the safety, toxicity, and tolerance of each treatment arm. While indinavir is currently the most commonly prescribed protease inhibitor, the optimal therapy for a person on an indinavir-containing regimen who experiences a rebound in viral load or never experiences a decrease in viral load below 500 copies per milliliter is unknown. Current clinical practice for such patients typically involves empiric use of a combination of other protease inhibitors (saquinavir/nelfinavir or saquinavir/ritonavir) and at least 1 other antiretroviral agent to which the patient has had little or no prior exposure. This may involve the use of 1 or more reverse transcriptase inhibitors (RTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs). This study attempts to formally evaluate some of these options in indinavir-experienced patients.

Timeline

Start

—

Primary completion

—

Completion

1999-08

Publications

• Background Gulick RM, Hu XJ, Fiscus S, Fletcher CV, Haubrich R, Cheng H, Lagakos S, Acosta E, Swanstrom R, Mills C, Snyder S, Fischl M, Pettinelli C, Katzenstein D. Durability of salvage therapy with saquinavir SGC (SQV) in combination with ritonavir (RTV) or nelfinavir (NFV) plus delavirdine (DLV), adefovir dipivoxil (ADV), or both; ACTG 359: 48-week final results. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 338)
• Background Acosta EP, Gulick R, Katzenstein D, Haubrich R, Fischl M, Raasch R, Mills C, Pettinelli C, Remmel RP, Fletcher CV. Pharmacokinetic (PK) evaluation of saquinavir soft gel capsules (SQV)/ritonavir (RTV) or sqv/nelfinavir (NFV) in combination with delavirdine (DLV) and/or adefovir dipivoxil (ADV) - - ACTG 359. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:136 (abstract no 365)
• Background Gulick RM, et al. Salvage therapy with saquinavir sgc (SQV) in combination with ritonavir (RTV) or nelfinavir (NFV) and delavirdine (DLV), adefovir dipivoxil (ADV), or both-ACTG 359. Second International Workshop on Salvage Therapy for HIV Infection. 1999 May 19-21
• Background Fletcher CV, Testa MA, Haubrich R, Brundage R, Jiang H, Ickovics J, Martinez A, Snyder S, Gulick R. Relationships among Four Measures of Medication Adherence and Virologic Response in ACTG 359. 10th Conference on Retroviruses and Oppurtunistic Infections. Feb 2003. Abstract 577.
• Results Gulick RM, Hu XJ, Fiscus SA, Fletcher CV, Haubrich R, Cheng H, Acosta E, Lagakos SW, Swanstrom R, Freimuth W, Snyder S, Mills C, Fischl M, Pettinelli C, Katzenstein D. Randomized study of saquinavir with ritonavir or nelfinavir together with delavirdine, adefovir, or both in human immunodeficiency virus-infected adults with virologic failure on indinavir: AIDS Clinical Trials Group Study 359. J Infect Dis. 2000 Nov;182(5):1375-84. doi: 10.1086/315867. Epub 2000 Oct 9.
• Results Gulick RM, Hu XJ, Fiscus SA, Fletcher CV, Haubrich R, Cheng H, Acosta E, Lagakos SW, Swanstrom R, Freimuth W, Snyder S, Mills C, Fischl M, Pettinelli C, Katzenstein D. Durability of response to treatment among antiretroviral-experienced subjects: 48-week results from AIDS Clinical Trials Group Protocol 359. J Infect Dis. 2002 Sep 1;186(5):626-33. doi: 10.1086/342681. Epub 2002 Aug 9.
• Results Fletcher CV, Jiang H, Brundage RC, Acosta EP, Haubrich R, Katzenstein D, Gulick RM. Sex-based differences in saquinavir pharmacology and virologic response in AIDS Clinical Trials Group Study 359. J Infect Dis. 2004 Apr 1;189(7):1176-84. doi: 10.1086/382754. Epub 2004 Mar 16.
• Results Swanstrom R, Bosch RJ, Katzenstein D, Cheng H, Jiang H, Hellmann N, Haubrich R, Fiscus SA, Fletcher CV, Acosta EP, Gulick RM; AIDS Clinical Trials Group Protocol 359 Team. Weighted phenotypic susceptibility scores are predictive of the HIV-1 RNA response in protease inhibitor-experienced HIV-1-infected subjects. J Infect Dis. 2004 Sep 1;190(5):886-93. doi: 10.1086/422692. Epub 2004 Jul 23.
• Results Fletcher CV, Testa MA, Brundage RC, Chesney MA, Haubrich R, Acosta EP, Martinez A, Jiang H, Gulick RM. Four measures of antiretroviral medication adherence and virologic response in AIDS clinical trials group study 359. J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):301-6. doi: 10.1097/01.qai.0000180078.53321.6a.
• Results Haubrich RH, Jiang H, Swanstrom R, Bates M, Katzenstein D, Petch L, Fletcher CV, Fiscus SA, Gulick RM; AIDS Clinical Trials Group Protocol 359 Team. Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. HIV Clin Trials. 2007 Mar-Apr;8(2):63-7. doi: 10.1310/hct0802-63.

Drugs

Indications