PROVIDENCE, R.I. - A new multi-site study reveals patients with drug-resistant HIV can safely achieve viral suppression - the primary goal of HIV therapy - without incorporating the traditional class of HIV medications into their treatment regimen. Karen Tashima, M.D., director of the HIV Clinical Trials Program at The Miriam Hospital, served as study chair.
The AIDS Clinical Trials Group (ACTG) Network's OPTIONS Trial proves, for the first time, that treatment-experienced patients can leave out this class of medication, known as nucleoside reverse transcriptase inhibitors (NRTI), as part of the regimen. These results could change treatment guidelines, lessen side effects and increase adherence rates, the researchers say.
Tashima and colleagues presented the results from the 48-week study at the annual Conference for Retroviruses and Opportunistic Infections (CROI) in Atlanta on March 6.
"We are so comfortable clinically with the NRTI class that we think we must always use at least one drug from this class in treatment. However, some patients have developed within-class resistance, making the NRTIs less effective overall. Therefore, drugs from this class may not be needed if the new treatment plan contains more effective medications," said Tashima, who also leads ACTG's clinical research site at The Miriam Hospital.
"There were a few new drugs coming out at the same time and we decided to turn the question around. Instead of having patients take their current medications from the NRTI class as well as these new drugs from different classes, we asked half of the study participants to add NRTIs and half of them to leave out NRTIs from their new treatment plan. We were able to take the usual study paradigm and turn it around," she added.
Treatment-experienced patients can develop resistance to therapy due to poor adherence, said Richard Haubrich, M.D., the study's co-chair and professor of medicine at University of California at San Diego. Designing a treatment plan using new drugs from new classes and omitting NRTIs leads to fewer pills, and hopefully, better adherence.
"There are several options for treatment naïve patients, but not as many for treatment-experienced. The HIV research field accepted that nucleosides would be an important component for multiple class-experienced patients," said Haubrich. "However, our results were very clear. We can safely exclude NRTIs, giving physicians a new paradigm for ART prescription in clinic and potentially changing treatment guidelines."
To ensure eliminating NRTIs from their treatment regimen would not be detrimental for viral suppression, investigators used a web utility to review each of the 413 study participants' study records to determine optimal treatment plans. This tool allowed all of the study's investigators to consult together on each study participant, offering the best plan for treatment.
The OPTIONS Trial, also called A5241, included ACTG sites from around the country as well as sites from the International Maternal Pediatric Adolescent AIDS Clinical Trials group and the Adolescent Medicine Trials Network. Study volunteers needed to be at least 16 years old and show treatment experience or resistance to their current HIV medications. Most of the A5241 participants had been on ART for 10 years or more.
Traditional antiretroviral therapy consists of medications from the nucleoside reverse transcriptase inhibitor class, including tenofovir, azidothymidine and lamivudine. The new medications studied included darunavir and tipranavir from the protease inhibitor class of HIV medications, maraviroc from the CCR5 antagonist class, raltegravir from the integrase inhibitor class, etravirine from the non-nucleoside reverse transcriptase inhibitors class and enfuvirtide an injectable drug from the fusion inhibitor class.
Patients will continue on study for a total of 96 weeks to ensure virologic suppression is maintained.
"There is no question that the results show what we had set out to prove - a treatment-experienced patient will not lose virologic suppression by omitting NRTIs," said Tashima. "We are so excited to show this data."
This research was supported by the U.S. Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), the National Institute of Allergy and Infectious Diseases (NIAID) and the Division of AIDS (DAIDS) under awards 5U01AI069472 and UM1-A1068636.
The principal affiliation of Karen Tashima, M.D., is The Miriam Hospital (a member hospital of the Lifespan health system in Rhode Island). Tashima is also a professor of medicine at The Warren Alpert Medical School of Brown University.
The AIDS Clinical Trials Group (ACTG) Network's Leadership and Operations Center (LOC) is based at Brigham and Women's Hospital in Boston. The ACTG Network's mission is to develop and conduct scientifically rigorous translational research and clinical trials to (1) investigate the viral and immune pathogenesis of HIV-1 infection and its complications; (2) evaluate novel drugs and strategies for treating HIV-1 infection; (3) evaluate interventions and strategies to treat and prevent HIV-related co-infections and co-morbidity, and; (4) publish and disseminate results to improve care, and reduce or eliminate morbidity and mortality associated with HIV-1 infection and its complications. The Network has 73 research sites around the world, including 50 domestically and 23 abroad.
The Miriam Hospital is a 247-bed, not-for-profit teaching hospital affiliated with The Warren Alpert Medical School of Brown University. It offers expertise in cardiology, oncology, orthopedics, men's health, and minimally invasive surgery and is home to the state's first Joint Commission-certified Stroke Center and robotic surgery program. The hospital is nationally known for its HIV/AIDS and behavioral and preventive medicine research, including weight control, physical activity and smoking cessation. The Miriam Hospital has been awarded Magnet Recognition for Excellence in Nursing Services four consecutive times and is a founding member of the Lifespan health system. Follow us on Facebook and on Twitter (@MiriamHospital).