Approval Of Atripla For HIV Called 'Extraordinary'

Review


The FDA has approved a once-daily tablet called Atripla for HIV, a simple regimen that is being hailed as an "extraordinary accomplishment."

Each Atripla pill contains 600 mg of Sustiva (efavirenz), 200 mg of Emtriva (emtricitabine), and 300 mg of Viread (tenofovir DF), which are three of the most commonly used anti-HIV medications.

The development of single-pill, once-daily dosing has long been a goal of HIV researchers, because taking antiretroviral medication faithfully is a key factor in keeping the virus in check. However, some of the early regimens of highly active antiretroviral therapy (HAART) mean that patients were taking dozens of different pills, many times a day, either with food or without.

The co-formulation required the cooperation of three major pharmaceutical companies -- Bristol-Myers Squibb, Gilead Sciences, and Merck. Atripla was approved in less than three months, under the FDA's fast track program, and the medication is expected to be available in the U.S. within days, the FDA said.

The drug will also be eligible for use in 15 other countries included under the President's Emergency Plan for AIDS Relief (PEPFAR), the agency said.

The three medications in combination have been shown over the past few years to be the safest and the most effective regimen for HIV patients, especially those who are beginning treatment.

"It's not simply that we found three pills that could be squished together into one tablet," commented Cal Cohen, M.D., research director of the Community Research Initiative of New England. "We found three of the best medications that could be co-formulated."

But Dr. Cohen stressed that even though the Atripla regimen is simple and safe -- "one pill is not that scary," he said -- it shouldn't be interpreted as a sign that prevention efforts should be relaxed.

"We don't want people to think that HIV is no longer worth avoiding," he said.

"To the extent that pill burden is one of the factors that contributed to people not taking their pills as they needed to control the virus, this is a big step forward," Dr. Cohen said.

Atripla will mainly be useful for patients who are treatment-naïve, he said, since resistance to one of the components will make it less effective. But treatment-experienced patients who have no resistance to Sustiva, Emtriva, and Viread will be able to take Atripla.

The co-formulation has not been tested in the presence of food, so patients are advised to take it on an empty stomach. Also, since Sustiva is known for neurological disturbances in the first few weeks of therapy -- vivid dreams, dizziness, and impaired concentration -- the drug should be taken at bedtime.

The Atripla labeling includes a warning that the drug's use can cause lactic acidosis. It is not approved for patients with chronic Hepatitis B infection, but if they are taking Atripla, discontinuation can result in severe flare-ups of Hepatitis B. The labeling also warns that serious adverse events reported for Atripla's ingredients include liver toxicity, renal impairment, and depression.

In the combination, Sustiva is a non-nucleoside reverse transcriptase (RT) inhibitor, while Emtriva and Viread are nucleoside RFT inhibitors. The combination does not include a member of the third major class of anti-HIV drugs, the protease inhibitors.

The FDA said Atripla is meant to be taken alone or "in combination with other antiretroviral products." But Dr. Cohen said it's unlikely that Atripla will form the basis of a super-HAART, with many drugs instead of just three. "At this point, we have no information that suggests we need more than three drugs," he said.

Atripla was approved on the basis of the original approvals for the three components, as well as a clinical trial of 511 treatment-naïve patients that compared the three drugs as a regimen against Combivir (lamivudine and zidovudine) and Sustiva. In that 48-week, open-label study, 84% of patients in the Sustiva/Emtriva/Viread arm reached less than 500 copies HIV RNA per milliliter of plasma, compared with 73% in the other arm.

Also, the mean increase from baseline in CD4 cell count was 190 cells per cubic millimeter for Sustiva/Emtriva/Viread, and 158 cells per cubic millimeter for Combivir/Sustiva.