HIV patients who take their HIV drugs intermittently are at a greater risk of infections, heart disease, and death compared to those patients who never stop taking their medicine, according to a new study in the New England Journal of Medicine.
This finding could end a long debate on the value of "drug holidays," an approach otherwise known as standardized treatment interruption (STI) and a popular strategy in the war against HIV and AIDS over the past five years.
"This is a very important study," says Dr. Paul Skolnik, director of the Center for HIV/AIDS Care and Research at Boston University Medical Center in Boston, Mass. "It was controversial at the time it was designed, because there were many who fervently believed, despite the lack of data, that drug interruption was the correct way to go."
STI was initially designed to mitigate the serious side effects of HIV medications in patients, including changes in body fat, liver problems, and heart disease. Patients following STI would take a break when their immune systems were strong and start taking the drugs again when their bodies' natural defenses were down.
The Strategies for Management of Antiretroviral Therapy (SMART) study, which looked at nearly 6,000 patients in 33 countries, revealed that patients who stopped and started their drug regimens experienced a 2.6 times greater risk of infectious disease or death.
"Much of HIV treatment over the years has, unfortunately, been based on anecdotal or limited evidence," Skolnik says. "We have learned time and time again that these kinds of decisions can only be wisely made through adequately controlled and designed studies."
No Benefit for Side Effects
Additionally, though it was hoped that occasional breaks in drug regimens would minimize drug side effects, patients in the STI group still had nearly double the chance of having major heart, liver, or kidney problems.
In fact, the study was stopped early due to the poorer outcomes in the STI group.
"It was surprising that death rates and cardiac disease tended to be higher in the interruption group," says Dr. Jeffrey Lennox, professor of medicine and principal investigator for the Emory AIDS Clinical Trials Unit, in Atlanta, Ga.
"The SMART study shows that stopping or interrupting therapy is not smart," says Dr. Carlos del Rio, director for clinical sciences and international research, Emory Center for AIDS Research in Atlanta, Ga. "This is clearly a landmark publication."
Though the findings may be a disappointment to many doctors and patients who held high hopes for STI, experts say the study is an important step in ensuring the best treatment strategy possible for HIV and AIDS patients.
"This study is important because it directly addresses the question: 'What is better for the patient?'" says Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. "Other studies that were done were not done long enough or with enough patients."
What Does It Mean for Patients?
The findings of the study have the potential to impact the treatment decisions of the more than one million Americans currently living with HIV.
Lennox says the study will reassure many patients who are worried about the toxicity of their HIV treatments.
"That was one of the primary reasons for doing this study," he says. "The hope was that by intermittently treating patients, [we] would minimize toxicity. It seems that ...viral replication being suppressed is [perhaps] more important."
Fauci says the study shows that the heart, kidney and liver effects once thought to be associated with drug treatment "must be associated with the fact that they have active viral replication going on in these tissues."
Other physicians also say the findings will help many doctors and patients take a step in the right direction with regard to drug therapy.
"I advise all my interested patients to read a Web summary of this study," says Dr. Charles Carpenter, director of the Brown University AIDS Center in Providence, R.I.