Betsy Adams, a nurse and the manager of clinical research at the Center for HIV/AIDS Care and Research (CHACR) at Boston University Medical Center, is disappointed whenever she learns that a patient is reluctant to participate in the center’s clinical trials of new drugs in the fight against HIV, the virus that leads to the immune system disease AIDS, which kills thousands of Americans and millions worldwide every year. But she also understands their reservations.
“People get nervous about confidentiality,” says Adams. “They worry that they may be taken advantage of or treated like guinea pigs.
“In fact,” she says, “patients in clinical trials always get the best care, because they’re monitored so closely. In standard of care, they might be seen by a doctor every three months, but they’re seen weekly by us.”
Soon Adams will be able to offer patients one of the most promising drugs to come out of the lab — one of an entirely new class of drugs known as integrase inhibitors, dubbed the “Holy Grail” of HIV treatments by some in the research community. Within the next three weeks, CHACR will begin enrolling patients in trials of two drugs from this new class, one developed by Merck & Co, Inc., and the other by Gilead Sciences, Inc.
Over the past two decades, researchers have developed four classes of HIV drugs. Each of them targets a different stage in the life cycle of the HIV virus, which attaches to cells within the body’s immune system and hides its proviral DNA inside the host cell’s DNA in order to make copies of itself that can infect other cells. Integrase inhibitors, the most recent class of drugs to be developed, work by preventing the virus from integrating its DNA into the host cell’s DNA. (Click here to watch a video about how integrase inhibitors work.) To date, however, researchers have been unable to develop an integrase inhibitor that is both safe and effective.
That may be about to change. In order to be approved by the Food and Drug Administration (FDA), new drugs must undergo three phases of clinical trials to test for safety, side effects, and proper dosage and to prove that the new treatment is better than the current standard of care. The Merck and Gilead integrase inhibitors that will be tested at CHACR are now entering phase III and phase II clinical trials, respectively.
“I’ve been hearing mention of integrase inhibitor work for at least eight years,” says Davidson Hamer, a School of Public Health associate professor and a research associate with the SPH Center for International Health, who is a co-investigator in the Merck clinical trial. “It’s very exciting, because if these succeed, it will add a whole new approach to HIV treatment.”
The possibility of a new approach comes at a critical time in the fight against HIV/AIDS. Worldwide, HIV infections continue to climb. The number of people infected hit 40.3 million in 2005, up more than 7 percent in just two years, according to the World Health Organization. Here in the United States, after dramatic declines in the 1990s, the number of people whose HIV has developed into AIDS has been edging up in the last few years. According to the Centers for Disease Control (CDC), the number of AIDS diagnoses in America rose from a few hundred in the early 1980s, when doctors first recognized the disease, to a peak of nearly 80,000 in 1993. Drug advances and prevention efforts brought new diagnoses down to 39,200 by 2001. But, by 2004, the latest year for which CDC data is available, the number of new cases had increased to 42,500.
The integrase inhibitor trials will involve hundreds of patients spread among several clinical sites in Europe and the United States, including the BU center, which typically has about 15 ongoing clinical trials. CHACR trials include those sponsored by drug companies (such as the Merck and Gilead trials) as well as federally funded trials through the Aids Clinical Trial Group, administered by the National Institutes of Health.
Founded in 2001, CHACR provides HIV testing, clinical care, pharmacists, nutritionists, support groups, social services, and on-site liver, lung, cancer, and psychiatric specialists. Paul R. Skolnik, a School of Medicine professor of medicine, chief of the BMC section of infectious diseases, and CHACR founder and director, emphasizes that clinical trials are crucial to both advancing research and giving HIV patients the best possible treatment.
“I fully believe that to have optimal HIV care, you have to give patients access to these clinical trials of the cutting-edge, experimental treatments,” says Skolnik. The upcoming integrase inhibitor trials will each last 48 weeks, but patients who react well to the drug will be allowed to keep taking it, and those in the placebo group who do not improve will have the option of switching over to the drug after about 12 weeks.
The patients who will help test the new integrase inhibitors will be those who have already undergone extensive drug therapy, indicating that the virus infecting them is particularly hardy and resistant to existing drugs. “These are patients who have few options left,” Skolnik explains. “It’s basically the acid test. If the drugs work in this group, they’re more likely to work with [less resistant viruses].”