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TheBody.com/TheBodyPRO.com covers The 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010)

Once-Daily "Extended" Formulation of Nevirapine Holds Up Well in 48-Week Study Results

September 15, 2010

A once-daily, extended-release form of Viramune (nevirapine) in development appears to be as safe and effective as the twice-daily, immediate-release form currently on the market, according to 48-week study results presented at ICAAC 2010.

Viramune is typically taken as a 200-mg pill twice a day, although people who are just beginning Viramune treatment often take the 200-mg pill just once a day for the first couple of weeks to reduce the risk of side effects. The extended-release form of Viramune in development (Viramune XR for short) doubles the dose to 400 mg, allowing for it to be taken once-daily.

The VERxVE study (pronounced "verve" -- apparently, the x is silent) is a clinical trial backed by the drug's developer to determine whether Viramune XR works as well as the twice-daily form available today. Joseph Gathe, M.D., presented 48-week results from this trial; these same results were also presented at AIDS 2010 in Vienna two months ago.

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The trial ultimately involved 1,011 HIV-positive people who had never before been on antiretroviral treatment. This was a pretty diverse group of volunteers, as clinical trials go: 15 percent were women (and were required to have a CD4 count below 250, since a higher CD4 count has been associated with dangerous adverse events in women taking Viramune), around 20 percent were black, and about half lived in Europe, with the rest divided among Africa, Australia, Latin America and North America.

After taking the 200-mg form of Viramune once a day for two weeks (the "lead-in" period designed to avoid side effects), the group was split in half; each half received Truvada (tenofovir/FTC) and was randomized to also receive either Viramune twice-daily or Viramune XR. At 48 weeks, 81 percent of people on Viramune XR versus 76 percent of people on twice-daily Viramune had a viral load below 50, meeting the "non-inferiority" criteria set by the study designers. (That said, Viramune XR appeared even more effective among people who entered the study with a viral load below 100,000; 86 percent of those people achieved an undetectable viral load on Viramune XR, compared to 79 percent on twice-daily Viramune. Viramune XR was less impressive among people with a baseline viral load above 100,000: Within that group, 73 percent of those on Viramune XR achieved an undetectable viral load, compared to 71 percent on twice-daily Viramune.)

One concern with once-daily doses of drugs that had previously been available only in a twice-daily form is that the once-daily version will fail to maintain high enough levels in a person's blood to stave off the development of drug resistance. The VERxVE study found that trough concentrations of Viramune XR (i.e., the lowest level of the drug within the blood) were consistently about 20 percent below that of twice-daily Viramune; however, Gathe noted that even that lower level far exceeded the minimum concentration of the drug necessary to maintain its effectiveness.

One other concern is that adverse effects already associated with the twice-daily dose could become exacerbated in a switch to a once-daily version. VERxVE appears to alleviate such concerns, however; through 48 weeks, the number of adverse events was similar across both study arms. Hepatobiliary problems (those related to the liver or gall bladder) and rash (including Stevens-Johnson syndrome), two types of adverse events that are particularly associated with Viramune use, didn't happen any more frequently among people on Viramune XR than among people on twice-daily Viramune; if anything, those adverse events tended to occur a little less frequently, and no new types of side effects emerged during the study. (In response to an audience question, Gathe said he did not know whether any of the study participants had hepatitis B or C, which could potentially affect the liver findings.)

Gathe said that impact on lipid levels was similar across both study arms: LDL and HDL cholesterol levels both increased approximately 10 percent, and the ratio of total cholesterol to HDL dropped by about 14 percent. He said no data were available yet regarding body fat changes among the study participants.

It's still likely to be some time before Viramune XR is approved for use in the U.S. Gathe, as the (arguably biased) study presenter, said that, were the drug approved, he would feel comfortable either switching his Viramune twice-daily patients to Viramune XR or simply starting them on Viramune XR in the first place once the two-week lead-in period was over. The key, according to Gathe, was assuring that a person's regimen consisted of antiretrovirals that all had as similar a dosing schedule as possible. "As a clinician, I think dosing symmetry is much more important, as long as it looks like virological efficacy is the same," he said in response to an audience question during his presentation. "It's much more difficult for a patient to take one drug once a day and the other drug twice a day, versus being able to take all the drugs at one time."

For now, however, the discussion is moot, as the drug is still moving through the development process. The VERxVE study will continue out through 144 weeks, and Gathe noted that studies on genotypic resistance data and the drug's activity in children were upcoming.

Myles is the editorial director of TheBody.com and TheBodyPRO.com.


Reference

Gathe J, Knecht G, Orrell C, et al. 48 week (Wk) efficacy, pharmacokinetics (PK) and safety of once a day (QD) 400 mg nevirapine (NVP) extended release formulation (XR) for treatment of antiretroviral (ARV) naive HIV-1 infected patients (Pts) [VERxVE]. In: Program and abstracts of the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 12-15, 2010; Boston, Mass. Abstract H-1808.


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This article was provided by TheBodyPRO.com. It is a part of the publication The 50th Interscience Conference on Antimicrobial Agents and Chemotherapy.
 


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