A Study of Abacavir Plus Indinavir Sulfate Plus Efavirenz in HIV-Infected Patients

Summary

To compare the virologic response between abacavir (ABC, 1592U89) regimens (drug vs. placebo) and between the 2 dosing regimens (BID vs. TID) with respect to the proportion of patients with plasma HIV RNA levels below the limit of detection \[AS PER AMENDMENT 8/27/97: \< 500 copies/ml at week 16\]. To evaluate the safety and tolerance of the study arms. \[AS PER AMENDMENT 3/10/99: During the extension period, compare the time to detectable viremia (2 consecutive plasma HIV RNA levels greater than or equal to 500 copies/ml) between ABC and placebo.\] Therapeutically, there is a need to explore potent alternative therapy for patients who have received, or are currently receiving, a double nucleoside analog combination including lamivudine (3TC), a regimen that was proven to be clinically inferior to indinavir (IDV) when combined with zidovudine/3TC in study ACTG 320. In order to produce and maintain a maximal antiviral response, all patients in this study will receive 2 or 3 potent, new agents; ABC, a nucleoside analog, EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI), and IDV, a protease inhibitor. Virologically, the major question this protocol seeks to answer is how prior 3TC exposure in a dual nucleoside regimen influences the response to subsequent treatment. It is unclear whether it is best to add a protease inhibitor either 1) an NNRTI at 1 of 2 doses, or 2) an NNRTI at 1 of 2 doses plus a new nucleoside analog to achieve plasma HIV RNA levels that are below the limits of detection.

Timeline

Start

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Primary completion

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Completion

1999-09

Publications

• Background Squires K, Hammer S, Degruttola V, Fischl M, Grimes J, Demeter L, Morse G. Randomized trial of abacavir (ABC) in combination with indinavir (IDV) and efavirenz (EFV) in HIV-infected patients (pts) with nucleoside analog experience (NRTI exp). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:207 (abstract no LB15)
• Background Dicenzo R, Forrest A, Smith P, Squires K, Hammer S, Fischl M, Degruttola V, Morse G. Comparing intensive and sparse sampling for estimating the population pharmacokinetics (PK) of indinavir (IDV) in efavirenz (EFV)containing regimens. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 751)
• Background Landay AL, Bettendorf D, Chan E, Spritzler J, Schmitz JL, Bucy RP, Gonzalez CJ, Schnizlein-Bick CT, Evans T, Squires KE, Phair JP. Evidence of immune reconstitution in antiretroviral drug-experienced patients with advanced HIV disease. AIDS Res Hum Retroviruses. 2002 Jan 20;18(2):95-102. doi: 10.1089/08892220252779638.
• Results Demeter LM, DeGruttola V, Lustgarten S, Bettendorf D, Fischl M, Eshleman S, Spreen W, Nguyen BY, Koval CE, Eron JJ, Hammer S, Squires K. Association of efavirenz hypersusceptibility with virologic response in ACTG 368, a randomized trial of abacavir (ABC) in combination with efavirenz (EFV) and indinavir (IDV) in HIV-infected subjects with prior nucleoside analog experience. HIV Clin Trials. 2008 Jan-Feb;9(1):11-25. doi: 10.1310/hct0901-11.

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Indications