For Patients With AIDS, the Number of Pills may be Just as Important as the Type of Medication
SAN FRANCISCO, CA -- Based on an analysis of more than 3,000 patients involved in triple-drug combination trials to treat HIV infection, Duke University Medical Center researchers say that patients who take fewer pills tend to do better than patients who have more complex medication regimens.
The researchers speculate the reason is that patients who take fewer pills are more likely to adhere to their medication regimen - and therefore receive the greatest benefits of the therapy - than those on complex regimens, who may find it more difficult to take multiple pills at different times during the day.
The simplest of the regimens called for patients to take as few as four pills a day, while the more complex regimens involved taking 16 pills, taken at different times, some with food, some on an empty stomach.
"This study is an affirmation of our clinical experience that simpler regimens may lead to better treatment outcomes," said Dr. John Bartlett, director of clinical research at the Duke University Center for AIDS Research. Bartlett prepared the research findings for presentation to the Seventh Conference on Retroviruses and Opportunistic Infections. "The results of the current study would seem to emphasize the importance of developing drug regimens that are simple, potent and easy for patients to take.
"We assume that the reason for better outcomes is improved adherence, though this study was not designed to specifically address that question," Bartlett said. "Other studies have shown that fewer pills can lead to better adherence, but this is the first to demonstrate a link to better outcomes."
The researchers initially set out to perform a complex analysis of the effects of triple-drug combinations. They combined the results of 22 different trials involving a total of 3,115 patients who were being treated for the first time with anti-retroviral agents. These drugs interfere with the complex genetic machinery within the virus that allows it to make copies of itself.
The trials looked at the use of two nucleoside reverse transcriptase inhibitors (NRTI) in combination with one of the following class of agents: a protease inhibitor, a non-NRTI, or another NRTI. Thirteen unique drugs were represented in the trials - 10 of which have received FDA approval and three in Phase II clinical development
The results of their analysis showed that patients in all the trials did about the same after 48 weeks.
"However, in a subsequent analysis, we examined the relationship between the number of pills patients took and success of that treatment," Bartlett said. "Our results show that there is strong and statistically significant correlation between the number of pills and the success of the regimen."
In clinical trials for different anti-retroviral agents, the key marker of success is the number of copies of HIV genetic material (RNA) detectable in the blood. The number gives researchers an idea about how the virus is replicating, and for the study, levels of less than 50 copies per milliliter of blood indicate that a medication has been successful.
"We found that about 75 percent of patients on the simplest regimens had less than 50 copies of HIV RNA in their blood," Bartlett said. "In comparison, only about 20 percent patients with the most complex regimens had less than 50 copies. We know that levels less than 50 are an important indicator of a durable response to the medications."
"Importantly, in our analysis, we controlled for the kinds of drugs that were being used and their combinations," Bartlett said. "Even after this analysis, the pill count was still a statistically significant indicator of patient outcome."
According to Bartlett, there a number of prospective trials ongoing in which patients are being switched to more simple regimens to see if that has any effect on outcome.