July 12, 2004
The Gilead 903 study was an open-label, randomized clinical trial that compared tenofovir (TDF, Viread) with stavudine (d4T, Zerit). All of the patients in that study also received lamivudine (3TC, Epivir) and efavirenz (EFV, Sustiva, Stocrin). As has been presented at several prior meetings, the virologic outcomes in the 2 groups were equally good; the most recent results showed approximately 70% of both treatment groups achieving HIV-RNA levels <50 at 144 weeks by intent-to-treat analysis. The study presented here compared the safety data between the 2 arms for those patients who had hepatitis C virus (HCV) coinfection, with a particular focus on transaminase elevation.
Of the 600 antiretroviral-naive patients enrolled, HCV infection was found in 30/299 (10%) and 20/301 (7%) patients in the tenofovir and stavudine arms, respectively. At baseline, the mean alanine transaminase (ALT) level for these patients was 50 IU/L. At week 144, the ALT level had increased by 2.0 IU/L in the tenofovir group and 3.1 IU/L in the stavudine group, a non-significant difference. The aspartate transaminase (AST) levels were 0.3 IU/L and 5.7 IU/L for the tenofovir and stavudine arms, respectively, with a trend favoring tenofovir (P = .11). The rates of treatment-emergent grade 3/4 elevations (more than five times the upper limit of normal) also did not differ between the study arms. A relatively high proportion of patients in both treatment groups did not reach the 144-week follow-up point -- 14/30 for tenofovir and 11/20 for stavudine.
The good news is that both regimens were well tolerated in HCV-coinfected patients, with low rates of discontinuation due to liver toxicity. Prior analyses of this study have shown that adverse effects related to "mitochondrial toxicity," such as neuropathy and lipoatrophy, occurred cumulatively with somewhat higher frequency in the stavudine-treated patients. It is possible that the trend toward increased AST levels in the stavudine arm also reflect this toxicity, although the clinical importance of this isolated finding is likely to be small. The high discontinuation rate for HCV-infected patients overall probably reflects the frequent occurrence of co-morbid medical and psychosocial problems typically seen in patients with HCV/HIV coinfection.
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