July 14, 2003
As reported previously at several scientific meetings, the Gilead study 903 (for previous coverage, click here) found that tenofovir (TDF, Viread) was virologically similar to d4T (stavudine, Zerit) when combined with 3TC (lamivudine, Epivir) and efavirenz (EFV, Sustiva) in treatment-naive patients. However, the study elucidated important potential metabolic benefits associated with tenofovir therapy, with 96-week data outlined here.
Out of the 600 patients randomized 1:1 to each treatment arm, 82 percent of the tenofovir group and 78 percent of the d4T group had an HIV RNA level less than 50 at week 96 -- a non-significant difference and an outstanding result overall. For grade 3 or 4 adverse events, both arms were similar for clinical and laboratory abnormalities with the exception of triglycerides, which were elevated in 11 percent of the d4T-treated patients versus 2 percent of the tenofovir-treated patients. Further analysis of lipid changes showed also that d4T treatment was associated with greater increases in total and LDL cholesterol, but less of an increase in HDL cholesterol compared with tenofovir usage. Such changes led to a higher proportion of d4T subjects receiving lipid-lowering therapy -- 10 percent versus 2 percent.
In toxicities believed to be associated with mitochondrial dysfunction -- such as peripheral neuropathy, lipodystrophy, and lactic acidosis -- tenofovir overall had a lower number of events (4 percent) than d4T (20 percent), with the bulk of these made up of neuropathy and lipodystrophy. Indeed, tenofovir treatment showed significantly more limb fat by DEXA scan and greater weight gain (6.1 pounds vs. 0.8 pounds).
These follow-up data confirm the favorable metabolic profile of tenofovir compared with d4T, and encouragingly also demonstrate no differences between the two arms in renal function. Results such as these have rapidly made tenofovir a commonly-chosen agent for initial therapy.