A5391: Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide

HIV comorbidities and complications

Weight gain after starting HIV therapy is common, but recent studies have found that some people with HIV (PWH) who are taking an integrase inhibitor (INSTI) combined with a tenofovir alafenamide (TAF) regimen may gain more weight than people taking other drug combinations.  A rising number of PWH are overweight or obese, and a higher body mass index (BMI) increases the risk for diabetes, heart disease and stroke.

 

This study will include PWH who have been virally suppressed on a regimen consisting of an integrase inhibitor (INSTI) and TAF/FTC or TAF/3TC, and have a BMI of 30 kg/m² (the cut-off for obesity) or greater. This research study is trying to find out if they could gain less weight, or maybe lose weight, after switching to a regimen containing doravirine (DOR) with TAF/FTC (or TAF/3TC), or DOR with the related medication tenofovir disproxil (TDF/FTC [or TDF/3TC]) as compared to continuation of their current INSTI plus TAF regimen.

 

• To see if obese PWH on an INSTI-containing regimen can either reduce their rate of weight gain over time or even lose weight with a change to a different regimen.

• People living with HIV-1 who are at least 18 years of age
• Currently on an Integrase Inhibitor (INSTI) containing regimen (bictegravir, dolutegravir or raltegravir) plus TAF/FTC (or TAF/3TC) for at least 48 weeks
• HIV viral load less than 50 copies
• Have a body mass index (BMI) at least 30 kg/m².
• No plans to undergo weight loss surgery or to start significant exercise, diet, or medications affecting weight (e.g., structured weight loss programs such as Weight Watchers)

Participants will be randomized to one of three study groups:

Group 1: DOR and continue taking TAF/FTC (or TAF/3TC)

Group 2: DOR and switch TAF to TDF/FTC (or TDF/3TC)

Group 3: Continue current INSTI+TAF/FTC (or TAF/3TC)

 

Study procedures include blood and urine tests, questionnaires about adherence to medications, diet and exercise habits, and DEXA Scans to measure lean muscle, body fat and bone density.

Doravirine, which is an FDA-approved antiretroviral drug for the treatment of HIV-1 and a member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) medication class, will be provided by the study.

 

NRTIs will need to be obtained by prescription from primary care provider.

 

Participants will be on study treatment for 48 weeks.