The public perception of AIDS treatment — a cocktail of many different pills taken several times a day and sometimes even in the middle of the night — has largely been erased in the United States thanks to advances in drug design and delivery.
Although textbook treatment guidelines still call for patients to take a few AIDS medications twice a day, many patients in industrialized countries now can keep sufficiently high medication levels in their bodies with once-daily doses.
Now researchers in an international collaborative that includes the Aids Clinical Trials Unit (ACTU) at Washington University School of Medicine in St. Louis have begun an ambitious new study to see if this treatment paradigm can be implemented in Third World countries.
Although the majority of participants in the new study will be in developing nations where AIDS infection rates are much higher than in the United States, nine U.S. AIDS treatment centers, including the Washington University ACTU, also are enrolling patients.
“The fewer times a day that AIDS patients have to remember to take their medicine, the better,” says David Clifford, M.D., the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology and director of the ACTU. “When patients miss scheduled doses, the virus jumps back very quickly and starts figuring out ways around the drugs. So we have to keep our foot on the virus and keep the virus nailed to the floor.”
To ensure compliance, AIDS physicians will sometimes ask patients to find a friend or family member who will make sure they take their medicine, a technique called direct observation.
“If monitors have to watch patients take their medicine once-a-day, that’s plausible,” Clifford says. “If they have to go four times a day, that’s hopeless.”
In the early days of AIDS drugs, one of the first successful treatments required patients to take a dose every four hours. Current AIDS drugs either contain larger doses, take advantage of strategies that release the medication into the body more slowly or incorporate features into the medicine itself that slow its clearance from the body.
Researchers administering the study are seeking AIDS patients who either have not yet been treated with antiviral medications or have had less than a week of such treatments.
International sites for the trial include South Africa, Zimbabwe, Thailand, India, Malawi, Peru and Brazil.
Clifford says there is evidence for optimism that the once-daily dosing schedule can be successfully implemented in developing nations. But he notes that many different factors may affect the success of the new approach in these areas.
One concern is that the brief treatment of HIV-infected pregnant women with antivirals to block mother-to-child transmission may have created reserves of drug-resistant HIV in developing nations. Although such treatment plans prevent the passage of AIDS to the infant, they often are stopped after birth, leaving versions of the virus that have begun to figure out ways of evading the drug treatments freeing the virus to multiply in the mother.
Scientists also are planning to look for signs that genetic differences in other nations alter patients’ responses to medications.
Economic feasibility also will be a concern. Many developing nations have large numbers of AIDS patients to treat but few resources. Also, the drugs that can be taken once daily tend to be among the most expensive treatments.
“This is the largest systematic trial of AIDS treatment to ever be conducted on a multinational stage,” Clifford says. “It’s really quite ambitious and exciting.”
The study is administered by the AIDS Clinical Trials Group, an NIH-funded network of 35 U.S. AIDS treatment centers of which the Washington University ACTU is a member.
Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.