Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the launch of the Do IT Study (Doravirine for Persons with Excessive Weight Gain on Integrase Inhibitors and Tenofovir Alafenamide), also known as A5391. The study will evaluate the effects of an antiretroviral (ARV) regimen change among people living with HIV who have experienced excessive weight gain when on a regimen that includes an integrase strand transfer inhibitor (INSTI) and tenofovir alafenamide/emtricitabine (TAF/FTC) or TAF/lamivudine (TAF/3TC).
While weight gain is common following initiation of most ARV regimens, recent studies have shown greater incidences of weight gain with some of the newer medications, such as combination therapies that include the INSTI class of drugs and TAF/FTC or TAF/3TC. Recent studies have also shown that greater incidences of weight gain while on ARV therapy increases the risk of developing co-morbid conditions such as diabetes and other chronic conditions among people living with HIV, particularly in those who are overweight or obese.
"Weight gain and the chronic conditions to which it often leads can have detrimental effects on the health and quality of life of people living with HIV," said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. "The ACTG is committed to undertaking research that optimizes ARV treatment and ensures optionality for people living with HIV."
A5391 is a phase 4, 48-week, open-label, randomized study to assess whether switching from the INSTIs bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL) with TAF/FTC or TAF/3TC to a new ARV regimen containing doravirine reduces weight gain or causes weight loss. Doravirine is a recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI); research suggests that individuals may gain less weight on NNRTI- and non-TAF-containing ARV regimens. The three arms of A5391 are:
- Doravirine + TAF/FTC or TAF/3TC
- Doravirine + tenofovir disoproxil fumarate (TDF)/FTC or TDF/3TC
- Continuation with current BIC-, DTG-, or RAL with TAF/FTC or TAF/3TC
A5391 will enroll a total of 222 adults living with HIV (74 per study arm) who have a body mass index (BMI) ≥27.5 kg/m2 and an unintentional weight gain of more than 10 percent of their body weight in the one to three years after starting an INSTI-containing regimen and TAF/FTC or TAF/3TC. Eligible participants must have also maintained virologic suppression for the 48 weeks prior to entry. All participants will be followed for 48 weeks to determine the effect of the medication switch on weight, body fat, blood glucose and metabolic health, and other parameters.
The trial is now enrolling participants at ACTG clinical research sites in the United States and may add other sites in South America and Africa.
"We are seeing an increase in chronic diseases linked to excess weight among people living with HIV," said A5391 Protocol Chair John Koethe, M.D., Vanderbilt University Medical Center. "We expect to gain valuable insights from A5391, the first rigorously designed study to determine if a change in antiretroviral medications may benefit people who have experienced excessive weight gain on INSTIs and TAF."
A5391 is led by Dr. Koethe; Jordan Lake, M.D., M.Sc. (University of Texas Health Science Center); and Roy (Trip) Gulick, M.D., M.P.H. (Weill Cornell Medicine). It is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and by Merck & Company, which is also providing study medications. NIAID and collaborating NIH Institutes fund the ACTG.
"While the benefits of current HIV drugs are well-known and appreciated, we need better strategies to manage their side effects, including weight gain," said Dr. Gulick. "We are hopeful that this study will inform the field in a way that benefits the overall health of people living with HIV."
