Gilead Sciences, Inc. announced preliminary three-year (144-week) data from a double-blind Phase III clinical trial (Study 903) suggesting that Viread (tenofovir disoproxil fumarate) is associated with similar levels of viral load suppression and a similar renal safety profile when compared to treatment with stavudine (d4T). At 144 weeks, treatment with stavudine was associated with greater elevations in fasting triglyceride and cholesterol levels and a notably higher incidence of investigator-defined lipodystrophy compared to treatment with Viread. These findings further extend the data from the 48- and 96-week analyses. The company anticipates presenting full data from this study at a scientific conference later this year.
Study 903 is the first three-year, international, randomized, double-blind, clinical trial of an HIV drug regimen in antiretroviral-naïve patients. In this study, 600 patients were randomized to receive either a treatment regimen of Viread, lamivudine and efavirenz (n=299) or stavudine, lamivudine and efavirenz (n=301) over 144 weeks.
"There is a great need for long-term clinical data evaluating the efficacy, durability and tolerability of antiretroviral regimens," said Joel Gallant, MD of Johns Hopkins University School of Medicine, and the study's principal investigator. "These results are important for both physicians and patients, who are increasingly interested in identifying well tolerated, convenient regimens that can be effective at suppressing HIV replication over an extended period of time without significant long-term toxicity."
At 144 weeks, data show that Viread and stavudine had comparable success in controlling viral replication, with 73 and 69 per cent of patients, respectively, showing a reduction of viral load to less than 50 copies/mL. The study discontinuation rate was comparable in each arm of the study, with 18 and 21 per cent of patients in the Viread and stavudine arms, respectively, discontinuing from the study. The most common adverse events observed were viral infection, diarrhea and headache, and each occurred with similar frequency in the two study arms.
Patients receiving Viread were less likely to develop investigator-defined lipodystrophy, characterized as changes in body shape, compared to those on stavudine, with three per cent of Viread patients developing this condition compared to 19 per cent of stavudine patients. In a sub-study designed to measure changes in limb fat, Viread patients had a mean total limb fat of 8.7 kg compared to 4.4 kg measured for those receiving stavudine. Loss of limb fat, or peripheral lipoatrophy, is a hallmark of lipodystrophy, which has been associated with long-term administration of some anti-HIV medications and with HIV disease.
Changes in fasting lipid levels (triglycerides and cholesterol) were notably higher in the stavudine treatment group. For patients receiving stavudine, the mean increase from baseline in triglycerides was 134 mg/dL compared to 1 mg/dL for those on Viread. Total cholesterol among stavudine patients increased by 58 mg/dL from baseline, compared to 30 mg/dL for those receiving Viread.
Data from the 144-week analyses suggest that resistance to Viread is slow to develop and occurs infrequently among treatment-naïve patients. In vitro data and earlier clinical trials show that Viread selects for K65R, a reverse transcriptase mutation. Through 96 weeks of the study, the K65R mutation developed in a total of eight patients (2.7 percent) in the Viread arm versus two patients (0.7 percent) in the stavudine arm. No additional cases of the K65R mutation were observed among patients in either arm of the study at 144 weeks.