Clinical trials of daily oral antiretroviral dosing as pre-exposure prophylaxis

Oct 3 2005

A truly colossal health problem, acquired immune deficiency syndrome will not go away -- at least no time soon.

The virus that leads to AIDS, human immunodeficiency virus, or HIV, caused an odd illness that was a complete medical mystery only about 25 years ago. Now, HIV infects more than 40 million people around the globe, and each day, some 14,000 more people pick up that infection, studies have shown.

While scientists continue to try to develop more effective drug treatments and possibly vaccines one day, and health educators counsel people to avoid risky behavior, still more weapons are needed to fight the stubborn scourge, they say.

Writing in the journal Science, an international team of researchers, clinicians and others explains that a promising, relatively new approach is for people not infected but at high risk to take drugs that might prevent them from contracting HIV. But debate over the particulars of the strategy has slowed progress.

"Even as available and proven prevention interventions are used, the HIV pandemic will not be stopped solely by talking to those at risk," they wrote. "Clinical trials of daily oral antiretroviral dosing as pre-exposure prophylaxis, or 'PrEP,' have been initiated in Africa, Asia and the United States and are planned in Latin America. Unfortunately, these trials have become controversial."

Authors of the commentary include Dr. Robert M. Grant, associate investigator at the Gladstone Institute of Virology and Immunology and associate professor of medicine at the University of California at San Francisco; Dr. Myron Cohen, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill schools of medicine and public health; and 16 others from as far away as Peru and Ghana. Cohen also is chief of infectious diseases at UNC Hospitals.

"HIV PrEP research, as with all aspects of the fight against HIV/AIDS, is built on partnerships between sponsors, investigators, communities and governments," the authors wrote. "Cooperation among such diverse interests is never easy, and coalitions are easily fractured by acts of disrespect, misinformation or miscommunication.

"Such acts occurred too frequently in the early days of PrEP research, and hard lessons have been learned on all sides. While good faith efforts are made to improve the conduct of trials, a balance must be struck between the necessity to conduct trials to very high standards and the need to find ways to prevent the spread of HIV infection."

Concerns about PrEP trials first generated widespread publicity during the International AIDS Conference in Bangkok in 2004. Following protests there, preparations for a drug trial in Cambodia were suspended. In February this year, the government of Cameroon did the same.

The most promising PrEP drug to date is tenofovir disoproxl fumarate or TDF, which has an excellent safety record. Gilead, the company that developed it, has established a global access program that will allow it to be sold at cost in 95 countries. It also plans to set up a non-exclusive licensing agreement with a drug manufacturer in South Africa.

"I think PrEP may prove to be a safe and cost-effective way to prevent HIV," Grant said. "We cannot know until the research is completed."

Other authors are Dr. Susan Buchbinder of the University of California at San Francisco, Dr. Edith Clarke of the Ghana Health Service in Accra, Ghana, Dr. Thomas Coates of the University of California at Los Angeles, Martin Delaney of Project Inform in San Francisco, Guiselly Flores of Peru's Women Living with HIV/AIDS and Dr. Willard Cates Jr., Dr. Kathleen M. MacQueen and Dr. Leigh Peterson of Family Health International.

Others are Pedro Goicochea, Dr. Jorge Sanchez and Dr. Javier Lama of the Health and Education Association in Lima, Greg Gonsalves of Gay Men's Health Crisis in New York, N.Y., Mark Harrington of Treatment Action Group also in New York City, Dr. John P. Moore of Cornell University's Weill Medical College, Dr. Melanie Thompson of the AIDS Research Consortium of Atlanta and Dr. Mark A. Wainberg of the McGill University AIDS Center in Montreal.