February 25, 2002
The FDA approved tenofovir disoproxil fumarate (TDF, Viread) in 2001 based on data showing antiviral activity in treatment-experienced patients. However, because of its excellent tolerability, good pharmacokinetics, and low pill burden (one tablet daily), there is considerable interest in using it in drug-naive patients as well. This small study provides a glimpse of the impressive antiviral activity that may accrue when the drug is used in those without baseline antiretroviral resistance.
Ten antiretroviral-naive patients were enrolled in this 21-day study of TDF monotherapy, given at the standard dose of 300 mg daily. During the first 72 hours, they were admitted to the inpatient unit of Rockefeller University for intensive monitoring, including frequent HIV RNA measurements. These measurements occurred at baseline, then every 6 hours for 72 hours, followed by daily for 7 days and again at days 12, 14, and 21.
At baseline, the group had a mean HIV RNA of 4.3 log, and a CD4 cell count of 645. At the end of the 21-day period, there was a mean viral load reduction of 1.5 log, with a range of 0.7-2.7 log. There was an accompanying increase in the CD4 cell count of 63 cells/mm3. Based on the intensive initial virologic monitoring, the slope of the rapid "first phase" of viral load decline was -0.39, which was comparable to historical data for ritonavir, which was -0.34. As reported previously by this research team, combination therapy with Kaletra/efavirenz/3TC/TDF not surprisingly achieves an even greater decline of -0.99.
It has been shown in several prior studies that the slope of this initial viral load reduction predicts the ultimate antiviral efficacy of a single drug or a combination regimen. As a result, the data from the present study argue that TDF has comparable antiviral potency to ritonavir, one of the first potent protease inhibitors.
Given TDF's other favorable characteristics described above, these results will undoubtedly encourage providers to consider using TDF as part of an initial combination regimen, a practice that has already been adopted by some clinicians, especially when constructing once-daily therapy. The ultimate widespread adoption of TDF as first-line therapy both in treatment guidelines and in practice await the results of the phase III study comparing TDF versus d4T, both in combination with 3TC and efavirenz. Data from this pivotal trial will likely be presented this summer at the International AIDS Conference in Barcelona.
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