Once-daily Viramune (nevirapine) is at least as effective as twice-daily dosing of the non-nucleoside reverse transcriptase inhibitor (NNRTI), according to a review of data from two European cohort studies presented on Monday at the 15th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
The U.S. Food and Drug Administration and regulatory agencies in other countries have approved Viramune only for twice-daily use. However, with the widespread availability of once-daily nucleoside reverse transcriptase inhibitors (NRTIs), interest in using Viramune once daily has grown, notably in Europe where Viramune is often prescribed once daily in clinical practice.
Some studies—including one reported at the 14th CROI held in Los Angeles in 2007—have suggested that once-daily Viramune may not be as effective as the twice-daily recommendation.
To further explore the relationship between once- and twice-daily Viramune dosing and the effectiveness of the drug, a team of researchers, under the direction of Alexandra Calmy, MD, of Geneva University Hospital, analyzed data from two European cohorts—the Dutch ATHENA study and the Swiss SHCS cohorts—in which patients received either dose of the drug in combination with other antiretrovirals.
Dr. Calmy’s group included 5,244 patients in its analysis, including 4,471 patients receiving twice-daily Viramune and 629 patients receiving once-daily Viramune. They also looked at treatment responses to once- and twice-daily Viramune using three main study characteristics: those who used either dose upon starting HIV treatment for the first time, those who switched to either dose after achieving an undetectable viral load with other antiretrovirals, and treatment-experienced patients with detectable viral loads who switched to either dose of Viramune.
Among those starting treatment for the first time with a Viramune regimen, 84 percent of the 82 patients on once-daily Viramune and 84 percent of the 771 patients on twice-daily Viramune had undetectable viral loads—below 50 copies—after two years of treatment. Dr. Calmy’s group noted that in this group of patients, it took longer for viral loads to go undetectable using once-daily Viramune.
Among those who switched to Viramune with an undetectable viral load, virologic responses were durable and comparable among the 1,507 using twice-daily Viramune and the 193 patients using once-daily Viramune for up to 96 weeks of follow-up.
Pretreated patients with detectable viral loads had better virologic outcomes with the use of once-daily, compared with twice-daily, Viramune. Time to viral load suppression was also shorter using once-daily Viramune in this population of patients, and gains in CD4 cell counts were significantly better in the once-daily Viramune group (an increase of 110 cells versus 80 cells in the twice-daily group).
“These data,” Dr. Calmy and her fellow authors suggest in the published study abstract, “suggest that once-daily nevirapine in clinical practice is at least as efficient as nevirapine prescribed twice a day. For patients with detectable [viral loads] who have been exposed to other antiretroviral drugs and [are] commencing a regimen including nevirapine, nevirapine once daily is associated with better and faster virologic suppression, as well as stronger immune restoration.”
February 9, 2008