Viread approved for HIV treatment
Treatments for HIV infection continue to evolve and be implemented rapidly. Consider Viread (tenofovir disoproxil fumarate, Gilead Sciences, Foster City, Calif.), the first nucleotide analog reverse transcriptase inhibitor approved by the Food & Drug Administration. Cleared in October, it is already available nationwide.
"It's got a different resistance profile that may make it helpful in some patients who've failed on other drugs," said Jeff Julian, Pharm.D., director and certified HIV pharmacist, Statscript Pharmacy, Kansas City, Mo. "It's one pill once a dayand convenience helps compliance," he said.
That tenofovir is "the first in a new category leaves us with all kinds of questions about where to position this drug in our cocktails and combinations," stated Bruce Olmscheid, M.D., director of HIV/AIDS education and training at St. Vincent's Hospital and Medical Center, New York City. "It has a resistance profile that is very unique in that it shows activity against many viral isolates that have varying degrees of resistance to existing nucleoside reverse transcriptase inhibitors [NRTIs]. And it has a very low development of resistance to itself in clinical trials to date."
In clinical trials, tenofovir reduced the HIV level in the blood for up to 48 weeks when added to patients' existing antiretroviral regimens, even in resistant patients. Side effects included mild to moderate gastrointestinal effects such as nausea, diarrhea, vomiting, and flatulence. But because lactic acidosis and severe hepatomegaly with steatosis have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals, tenofovir's package insert carries the standard black box warning. (In trials, patients who developed lactic acidosis were also on nucleoside analogs, so it is not certain whether the side effect is associated with tenofovir, particularly because tenofovir is largely excreted renally.)
Tenofovir doses will likely need to be modified in patients who are renally compromised, but dosing recommendations have not been determined. The package insert warns the drug should not be administered to patients with creatinine clearance of less than 60 ml/min. until more studies are completed.
Olmscheid expects tenofovir "will initially be used in what we call 'intensification,' which means patients already on an existing cocktail will all of a sudden show up at the pharmacy with a script for Viread, 300 mg, once a day, and there will be no other change to their regimen." This approach to therapy, adding just one drug to a failing regimen, "breaks a cardinal rule." But, he said, the cardinal rule changed when abacavir (Ziagen, GlaxoSmithKline) first demonstrated efficacy in intensification therapy.
The two tenofovir clinical trials submitted to the FDA for approval were intensification trials. "But I think pharmacists will very quickly see that Viread is going to be switched in and out [of regimens], just like one of the other NRTIs," Olmscheid commented. Results of tenofovir in treatment-naive patients will not be available until the trial is completed in February 2002.
Tenofovir will be used in combination therapy; thus, interaction with other antiretrovirals is particularly important. Notably, tenofovir significantly increases the maximum blood level and total absorption of didanosine (Videx, Bristol-Myers Squibb); tenofovir's package insert warns that this combination therapy should be monitored for long-term adverse effects.
Tenofovir also has lesser effects in decreasing the maximum blood level of lamivudine, indinavir, lopinavir, and ritonavir, as well as decreasing the total absorption of lopinavir and ritonavir, and increasing the minimum blood level of ritonavir. Indinavir and lopinavir/ritonavir (Kaletra, Abbott) can increase maximum tenofovir blood level. Lopinavir/ritonavir also increase total absorption and minimum blood level of tenofovir.
Julian expects tenofovir "to be on all the formularies." He noted, "There's no real secondary choicethere's no other option, and there's no generic. Some of the payers don't have it on [formulary] yet just because it's so new," but he is confident that will change.
Kathy Hitchens. HIV treatment advances with approval of first drug in new class.