Treatment Success and Failure in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs: A Rollover Study for ACTG 320

Summary

Group A: To compare the time to confirmed virologic failure (2 consecutive plasma HIV-RNA concentrations of 500 copies/ml or more) between the treatment arms: abacavir (ABC) or placebo in combination with zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV). To evaluate the safety and tolerability of these treatment arms. \[AS PER AMENDMENT 06/16/99: To compare the time to confirmed treatment failure, permanent discontinuation of treatment, or death between the treatment arms.\] \[AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable.\] Group B: To compare the proportion of patients who achieve plasma HIV-1 RNA concentrations below 500 copies/ml, as assessed by the standard Roche Amplicor assay at Week 16, or to compare the absolute changes in plasma HIV-1 RNA concentrations at Week 16 across the treatment arms: ABC or approved nucleoside analogs and nelfinavir (NFV) or placebo in combination with efavirenz (EFV) and adefovir dipivoxil. To compare the safety and tolerability of these treatment arms. Group C: To monitor plasma HIV-1 RNA trajectory over time and determine the time to a confirmed plasma HIV-1 RNA concentration above 2,000 copies/ml on 2 consecutive determinations for patients treated with ZDV or stavudine (d4T) plus 3TC and IDV. Group D: To evaluate plasma HIV-1 RNA responses at Weeks 16 and 48. To evaluate the safety and tolerability of the treatment arms: ABC, EFV, adefovir dipivoxil, and NFV. This study explores new treatment options for ACTG 320 enrollees (and, if needed, a limited number of non-ACTG 320 volunteers) who have been receiving ZDV (or d4T) plus 3TC and IDV and are currently exhibiting a range of virologic responses. By dividing the study into the corresponding, nonsequential cohorts (Groups A, B, C, D), different approaches to evaluating virologic success, i.e., undetectable plasma HIV-1 RNA levels, and virologic failure, i.e., plasma HIV-1 RNA levels of 500 copies/ml or more \[AS PER AMENDMENT 12/27/01: 200 copies/ml or more\], are explored while maintaining long-term follow-up of ACTG 320 patients. \[AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable. This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV (or d4T) plus 3TC plus IDV.\]

Timeline

Start

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Primary completion

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Completion

2003-06

Publications

• Background Henry K, Zackin R, Dube M, Hammer S, Currier J. ACTG 5056: metabolic status and cardiovascular disease risk for a cohort of HIV-1-infected persons durably suppressed on an indinavir-containing regimen (ACTG 372A). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 656)
• Background Hammer S, Squires K, Degruttola V, Fischl M, Bassett R, Demeter L, Hertogs K, Larder B. Randomized trial of abacavir (ABC) & nelfinavir (NFV) in combination with efavirenz (EFV) & adefovir dipivoxil (ADV) as salvage therapy in patients with virologic failure receiving indinavir (IDV). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:159 (abstract no 490)
• Background Hammer SM, Bassett R, Squires KE, Fischl MA, Demeter LM, Currier JS, Mellors JW, Morse GD, Eron JJ, Santana JL, DeGruttola V; ACTG 372B/D Study Team. A randomized trial of nelfinavir and abacavir in combination with efavirenz and adefovir dipivoxil in HIV-1-infected persons with virological failure receiving indinavir. Antivir Ther. 2003 Dec;8(6):507-18. No abstract available.
• Hammer SM, Ribaudo H, Bassett R, Mellors JW, Demeter LM, Coombs RW, Currier J, Morse GD, Gerber JG, Martinez AI, Spreen W, Fischl MA, Squires KE; AIDS Clinical Trials Group (ACTG) 372A Study Team. A randomized, placebo-controlled trial of abacavir intensification in HIV-1-infected adults with virologic suppression on a protease inhibitor-containing regimen. HIV Clin Trials. 2010 Nov-Dec;11(6):312-24. doi: 10.1310/hct1106-312.

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