October 29, 2001
One of the studies which provided a basis for approval of TDF was Study 907, a phase III, double-blind, placebo controlled, intensification study of treatment-experienced HIV-1 patients to determine the efficacy of TDF 300mg once daily as compared to placebo. The patients were stratified according to age (equal to or <40 and >40 years), gender and race (Caucasian and non-Caucasian).
All patients were on a stable antiretroviral therapy consisting of four or less agents for at least eight weeks prior to enrollment. Their plasma HIV-1 RNA viral loads were between 400 and 10,000 copies/mL and all had adequate renal, hepatic and hematologic function. Patients with infections requiring antibiotic treatment, patients with a new AIDS-defining event within 30 days, and pregnant or lactating patients were excluded.
There were a total of 552 patients enrolled in Study 907. The enrolled patients continued on their current antiretroviral therapy and were randomized in a 2:1 ratio to receive a full 48 weeks of TDF 300mg daily (368 patients) or 24 weeks of placebo followed by 24 weeks of TDF 300mg daily (184 patients). The time-weighted average change from baseline plasma HIV-1 RNA loads at week 24 (DAVG24) was the primary endpoint of Study 907. The DAVG24 of tenofovir DF was compared to the DAVG24 of placebo for the three subgroups (age, gender and race) using a Wilcoxon rank sum test to determine statistical significance. The results are not evaluated as to the effect of age, race or gender on the efficacy of TDF treatment, but only as it pertains to the relative efficacy of the placebo. For all patients, regardless of subgroup and within each individual subgroup, the TDF arm had a statistically significant decrease in DAVG24 as compared to the placebo arm. In addition, the TDF arm had a decrease in DAVG24 for patients regardless of CD4 cell count (<200 copies/mm3 or >200 copies/mm3) or baseline HIV-1 RNA viral loads (<5,000 copies/mL or >5,000 copies/mL) relative to the placebo arm.
The authors conclude that "tenofovir DF 300mg demonstrates activity as measured by DAVG24 across all baseline demographic and disease characteristics evaluated: race, gender and age [and] baseline HIV-1 RNA levels and CD4 cell count." These data show that TDF will function well in many distinct and important patient subgroups, although more information on its effectiveness in patients with high viral loads, those higher than 100,000 copies/mL, and very low CD4+ T cell counts, those with CD4+ T cell counts <50 copies/mm3 is needed, especially as consideration is given to using it as a part of a triple-drug regimen in patients who are naive or have minimal experience with antiretroviral therapy.