IAC: Pediatric HIV Drug Seen Safe and Effective

TORONTO, Aug. 17 -- An investigational pediatric version of a recently approved HIV drug is safe and well-tolerated at two different doses and appears to be effective, researchers said here.

The oral solution of Aptivus (tipranavir) boosted with Norvir (ritonavir) adds to the options for HIV-positive children and adolescents with a history of failing drug regimens, Juan Salazar, M.D., of the Connecticut Children's Medical Center in Hartford reported at the 16^th International AIDS Conference.

Young HIV patients often have difficulty with adult regimens, especially when they must swallow large numbers of large pills, Dr. Salazar said. "You can't give a two-year-old a big horse pill," he said. "This to me represents an alternative for children and young adolescents who can't take pills."

But while other types of HV medications have been converted to solution, the protease inhibitors, such as Aptivus, must be treated with powerful solvents, which usually leave an unpleasant and sometimes unbearable taste, he said.

Children on a protease inhibitor-based regimen of highly active anti-retroviral therapy (HAART) only have a few choices when it comes to a pediatric solution, Dr. Salazar said.

Dr. Salazar presented 48-week data from the Pediatric AIDS Clinical Trials Group 1051 study, which was aimed at finding the correct dose for children and young adolescents, but which also collected data on virological and immunological outcomes and adverse events.

The study, funded by the National Institutes of Health and the drug's maker, Boehringer Ingelheim, enrolled 115 children with a viral load of greater than 1,000 copies of viral RNA per milliliter of blood.

They were randomized to two dosages of Aptivus, taken twice a day. One contained 290 mg/m² and one with 375 mg/m². After discontinuations, 41 volunteers in the low-dose arm completed the study, compared with 47 in the high-dose arm.

At the beginning of the study, the average viral load was about 50,000 copies of viral RNA per milliliter of blood, Dr. Salazar said, and most of the participants were CDC Class C, meaning they had already had an AIDS-defining illness.

On an intent-to-treat basis at 48 weeks, he said, 39.7% of those on the low dose had suppressed their virus to below 400 copies of viral RNA per milliliter of blood, compared with 45.6% of those on the high dose. The difference wasn't significant, he said.

A lower proportion in each arm was able to suppress the virus to fewer than 50 copies, and the difference -- 34.5% versus 35.1% -- was also not significant, he said.

The median CD4 count increased by 157 cells per cubic millimeter of blood for those in the low-dose group and 96 in the high-dose group.

The virological and immunological changes are "not bad at all for this population," Dr. Salazar said, adding "these kids just have no options."

Protease inhibitors are the leading basis for pediatric AIDS regimens and "in treatment-experienced children, we don't have new options to offer them," commented Lindy Samson, M.D., chief of infectious diseases at the Children's Hospital of Eastern Ontario in Ottawa.

Dr. Samson noted that pediatric formulations tend to lag behind the adult versions, often by years. "We are running out of new protease inhibitors to offer," she said.

But it's not enough to reformulate adult regimens so they can be used by children, Dr. Samson said, "we need to make them palatable as well."

She said currently available formulations are by and large unpalatable, so that physicians and caregivers must resort to strategies such as giving a taste of chocolate or a thick milkshake before giving the medication.

Dr. Salazar said the new formulation of Aptivus/Norvir also does not have a pleasant taste.

The pediatric formulation of Aptivus/Norvir is not yet FDA-approved, Dr. Salazar said.