New research from an international team of HIV/AIDS experts led by Gladstone Institute investigator Robert Grant, M.D., M.P.H. in San Francisco and Peter Anderson, Pharm.D., at the University of Colorado, provides the first estimate of the drug concentration levels needed for Truvada to prevent the spread of HIV/AIDS.
The new study, available online in the September 12 Science Translational Medicine, builds on the 2010 iPrEx clinical study in which Dr. Grant and his colleagues found that Truvada could prevent new infections in people likely to come in contact with the virus. But questions about the drug's real-world effectiveness at preventing HIV transmission remain -- particularly concerning the issue of adherence to a regimen of taking a pill every day.
"After the initial iPrEx study, there was concern that the protective effect of Truvada was fragile, and that individuals taking the drug would need to adhere perfectly to a daily regimen for it to work," said Dr. Grant in a press release. He is also a professor at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. "This new study suggests that Truvada can help block the virus even if the person on a daily regimen doesn't always adhere perfectly."
Perfect adherence to drug regimens is notoriously difficult for people to accomplish, so the research team looked for a way to calculate Truvada's effectiveness while taking into account differing adherence levels.
The team developed a clinical trial in which they gave different amounts of the drug (two, four, or seven doses per week) to a cohort of 24 people without HIV. This resulted in different drug concentrations in blood drawn from each participant, thereby mimicking different levels of adherence. They then used a model to compare the drug concentrations in the blood of these participants to the concentrations of original iPrEx study participants in order to determine how well iPrEx participants adhered to the daily regimen, and how well they were protected against HIV at different levels of adherence.
"Surprisingly, we found that the iPrEx participants didn't have to adhere perfectly to the drug regimen to reap Truvada's benefits," said Dr. Grant. "Even in those patients who didn't adhere perfectly, their risk of contracting HIV still dropped by more than 90% -- offering a high level of protection against the virus."
This study is the first to establish an objective, quantitative method that estimates drug concentration levels and then correlates those levels with the drug's effectiveness at preventing transmission. These results could open the door to the exploration of ways to make dosing less costly, more convenient, and more adaptable to people's habits.
"Our immediate next step, however, is to take the methods we've developed and create simple yet powerful tools that can measure drug adherence to help doctors monitor how well Truvada is working in their patients," said Dr. Anderson. "Yet until these and other efficacy studies of alternative dosing strategies have been completed, the only regimen that should be used in clinical practice is the FDA approved one: one Truvada each day."
"Patients should still take one pill a day to achieve the best results, and we encourage people to explore multiple methods to prevent HIV -- such as regular condom use, early treatment of HIV infection in partners, good communication, and male circumcision," Dr. Grant said. "We hope that our findings lead to more effective use of prevention tools that finally squash the HIV/AIDS epidemic."