October 26, 2002
It has become increasingly popular and important to switch therapy in patients with fully suppressed viral loads. These switches can be done to simplify the regimen, to decrease the number of pills, to treat side effects, to decrease elevated lipids, or to try and avoid future side effects. This study looked at the effect of switching from d4T (stavudine, Zerit) to tenofovir (TDF, Viread) in patients with viral loads below 400 copies.
It was a retrospective review of 24 patients who were taking d4T, 3TC (lamivudine, Epivir), and a non-nucleoside and then switched the d4T for tenofovir. Since it was a retrospective study, the reasons for switching were varied. The largest number of patients (11) switched in order to simplify to once-daily therapy. Seven people switched because of neuropathy. Five switched because of lipoatrophy, and two people because they were co-infected with hepatitis B. (Tenofovir is very active against hepatitis B virus -- even when the virus has become resistant to 3TC.)
All patients also changed their 3TC to 300 mg once daily, and the 12 patients taking nevirapine (NVP, Viramune) changed from 200 mg twice a day to 400 mg once daily. Thus, all were changing to once-daily therapy.
After the switch, 20/24 patients continued to have viral loads below 400 copies. One patient was documented to be non adherent. Two had low-level rebounds but remained below 1,000 copies. They remained on the once-daily therapy.
One of the 24 patients developed frank viral failure. This patient failed with mutations at K65R (which confers resistance to tenofovir) and at K101E and Y188C (conferring resistance to non nukes). Interestingly, the replicative capacity, a measure of viral "fitness" generated by the Virologic assay, was very reduced at 15 percent.
The authors conclude that switching to once-daily therapy was well tolerated and successful in most but not all patients. There are limitations to this study, including the extremely small size and the retrospective nature. Nonetheless, it provides a rational for planning prospective studies of simplification and switching that puts patients on once-daily therapy. The actual reliability and durability of these once-daily regimens will have to be tested in prospective studies with larger numbers. Perhaps equally important, we cannot assume that once-daily therapy is the answer without studying it. Factors that may determine the success of once-daily therapy include patient preference, pill burden, pharmacokinetics and resistance. For an interesting exploration of patient preference, see the paper by Valerie Stone (Poster 486).
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