CTN 113: Adding 1592 (Abacavir) versus Adding Indinavir
A Phase III, Randomised, Double-Blind, Multicentre Study to Evaluate the Safety and Efficacy of 3TC/ZDV/1592U89 and 3TC/ZDV/IND in HIV-1 Infected, Antiretroviral Therapy-Naïve Subjects: Trial results
About the Study
Compare a combination of three reverse transcriptase inhibitors with a combination of two reverse transcriptase inhibitors and a protease inhibitor. Test the hypothesis that the two treatments are equivalent based upon proportions of volunteers with viral loads below 400 copies/ml at 48 weeks.
Study Approach
This international, randomized, double-blinded trial enrolled patients with viral load above 10,000 copies/mL, despite eight or more weeks of prior NRTI therapy, and no prior protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy. Volunteers were randomized to receive either indinavir (1,000 mg every eight hours) plus efavirenz (600 mg every 24 hours) or indinavir (800 mg every eight hours) plus matching placebo every 24 hours. In addition, all volunteers received no more than two concomitant NRTIs (zidovudine, lamivudine, didanosine, stavudine or zalcitabine).
Study Population
A total of 327 volunteers entered the study, beginning in April 1997. The mean duration of prior antiretroviral therapy was 2.8 years. About 76 percent of participants had at some time taken lamivudine. The mean viral load was 25,557 copies/ml. Despite enrollment criteria, 41 participants (26.1 percent) in the control group and 35 (20.5 percent) in the efavirenz group had viral load below 10,000 copies/ml at study entry. Median levels among these participants were 5,754 and 6,457 copies/ml in the control and efavirenz groups, respectively. About 68 percent of the participants in both groups changed the NRTI component of the regimen at study entry. Overall, 94 percent received two concomitant NRTIs, most commonly stavudine plus lamivudine (39 percent), zidovudine and lamivudine (24 percent), and didanosine plus stavudine (19 percent).
Results
A total of 327 volunteers entered the study, beginning in April 1997. The mean duration of prior antiretroviral therapy was 2.8 years. About 76 percent of participants had at some time taken lamivudine. The mean viral load was 25,557 copies/ml. Despite enrollment criteria, 41 participants (26.1 percent) in the control group and 35 (20.5 percent) in the efavirenz group had viral load below 10,000 copies/ml at study entry. Median levels among these participants were 5,754 and 6,457 copies/ml in the control and efavirenz groups, respectively. About 68 percent of the participants in both groups changed the NRTI component of the regimen at study entry. Overall, 94 percent received two concomitant NRTIs, most commonly stavudine plus lamivudine (39 percent), zidovudine and lamivudine (24 percent), and didanosine plus stavudine (19 percent).
Conclusions
The study demonstrated that, among patients with extensive prior NRTI experience and who continued to received NRTIs, treatment with efavirenz plus indinavir had significantly greater virologic efficacy at 24 weeks or more than did indinavir alone. It also confirms the effectiveness of efavirenz plus indinavir in lamivudine-experienced patients. Both treatment regimens were generally well tolerated.
Note: These results were taken from an article in The Journal of Infectious Diseases 2001;183:392-400.
