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Indinavir + ZDV + 3TC
Late Breaker Abstract
Abstract LB7
Potent and Sustained Antiretroviral Activity of Indinavir (IDV) in combination
with Zidovudine (ZDV) and Lamivudine (3TC).
Authors: R Gulick, J Mellors, D Havlir, J Eron, C Gonzalez, D McMahon, D Richman, F Valentine, L Jonas, A Meibohm, R Chiou, P Deutsch, E Emini and J Chodakewitz.
Preliminary results of a randomized, double-blind study comparing indinavir (800 mg three times per day) plus AZT (200 mg three times per day) plus 3TC (150 mg twice per day) or indinavir alone or AZT plus 3TC in 97 HIV-infected, 3TC-naive patients were presented. Patients had at least 6 months of prior AZT therapy with CD4 counts of between 50 to 400 cells/mm3 and 20,000 copies/ml or greater of serum HIV RNA.
At baseline, CD4 counts were about 142 cells/mm in all groups. Median CD4 increases from baseline at week 12 in about 28 patients per group were 79, 98 and 17 cells/mm3 in triple combination, indinavir alone, and AZT/3TC groups, respectively. At week 24, median CD4 increases from baseline in a subset of about 10 patients per group were 146, 77, and 22 cells/mm3 in the triple combination, indinavir alone, and AZT/3TC groups, respectively.
At baseline, patients had HIV RNA titer of about 39,800 copies/mL. Median reductions of 2, 1.3, and 1 log in viral RNA were achieved in the triple combination, indinavir alone, and AZT/3TC groups, respectively, over 24 weeks. A higher proportion of patients (7 patients) on the triple drug regimen (86%) had viral load levels declined to below assay detection limit, which was less than 500 copies/ml, as compared to those (9 patients) in indinavir monotherapy group (44%) at week 24. None (0%) had viral load reduction of less than 500 copies/ml in the AZT/3TC group.
The study medications were well tolerated for up to 32 weeks of follow-up. Two patients had developed nephrolithiasis on indinavir; both were able to continue without dose reduction. Hyper-bilirubinemia occurred in 15% of those taking indinavir which usually subsided. Neutropenia and/or anemia requiring dose reduction of AZT and 3TC occurred in some patients. Elevations in liver enzymes occurred in some patients and usually subsided within weeks. Preliminary pharmacokinetic analysis revealed no clinically significant interactions among the study medications.
Dr. Gulick concluded by saying that indinavir in combination with AZT and 3TC in heavily AZT pre-treated, HIV-infected people is a safe, well-tolerated regimen with potent antiretroviral activity and CD4 cell increases sustained for at least 24 weeks.
COMMENTS: Apparently, combining indinavir with AZT and 3TC is important to achieve sustained antiviral benefits. Many researchers believe that multi-drug combination therapy that includes a protease inhibitor is likely to delay the emergence of drug-resistant variants; thus, the duration of surrogate marker responses may be prolonged.
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