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Randomized Trial of Continued Indinavir (IDV)/ZDV/3TC vs. Switch to IDV/ddI/d4T or IDV/ddI/d4T + Hydroxyurea in Patients with Viral Suppression D. HAVLIR*1, P. GILBERT1, K. BENNETT1, A. COLLIER1, M. HIRSCH1, P. TEBAS1, E. ADAMS1, D. GOODWIN2, S. SCHNITTMAN3, M. K. HOLOHAN1, D. RICHMAN1, and the ACTG 5025 Study Team1.
1NIAID ACTG, Bethesda, MD; 2Glaxo Wellcome, Res. Triangle Park, NC; and 3Bristol-Myers Squibb, Wallingford, CT Background: Current antiretroviral treatment (ART) regimens still have unacceptable virologic failure rates. HU may improve VS by potentiating ddI activity, but may also increase toxicity.
Objective/Methods: To determine whether long term rates of VS and outcome could be improved with HU, subjects with >200 CD4 and HIV RNA <200 receiving IDV/ZDV(or d4T)/3TC were randomized to either continue this regimen (N=66), or switch to IDV/ddVd4T (N=68) or IDV/ddI/d4T/HU (N=68). HU dose was 600 mg bid. The primary study endpoint was a combination of loss of viral suppression (VIR) or drug toxicity (TOX) leading to ART discontinuation.
Results: Study population was 85% male, 10% IDU, median prior ART 1.8 yrs, median CD4 617. The study was prematurely discontinued (median F/U 31 weeks) after interim review. Primary endpoints were more frequent in the HU arm (7 VIR, 14 TOX) vs the IDV/ddI/d4T (6 VIR. 6 TOX) and the IDV/ZDV/3TC (3 VIR, 2 TOX) arms. Time to primary study endpoint was shorter in the HU arm vs the IDV/ddl/d4T arm (P=.05) and vs the IDV/ZDV/3TC arm (P<.001). Most common protocol-defined endpoint toxicities were pancreatitis and increased liver function tests. Time to ART limiting toxicity, but not virologic failure, was significantly shorter in the HU arm vs the other 2 arms. 3 deaths (2 from complications of pancreatitis) occurred in the HU arm. Median CD4 cell count (week 24) was significantly lower (101 cells below baseline) in the HU arm compared to the IDV/ddI/d4T (+27) and IDV/ZDV/3TC arm (+12), but CD4% were similar between study arms.
Conclusions: The addition of HU to potent. suppressive therapy did not enhance efficacy and was associated with excess toxicity.
Key Words: antiretroviral therapy, ddI, hydroxyurea
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