Weight gain after starting antiretroviral therapy (ART) is common, but recent studies have found that some people living with HIV (PLWH) who are taking an integrase strand transfer inhibitor (INSTI) combined with tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir alafenamide/lamivudine (TAF/3TC) may gain more weight than people taking other drug combinations. A rising number PLWH are overweight or obese. Higher BMI and weight gain on ART increase the risk for diabetes, heart disease and stroke. Researchers are looking to see if PLWH who have gained a significant amount of weight after starting or switching to an INSTI-containing regimen, can either reduce their rate of weight gain over time or even lose weight with a change to a different ART regimen. This study will include participants who are living with HIV-1, who have been virally suppressed for > 48 weeks on a regimen consisting of an INSTI and TAF/FTC or TAF/3TC and who have experienced > 10% weight gain since the initiation of this ART regimen.
Purpose of this Study: This research study is trying to find out if PLWH who had > 10% weight gain after starting an antiretroviral therapy (ART) regimen that included an INSTI in combination with TAF/FTC (or TAF/3TC) could gain less weight, or maybe lose weight, after switching to an ART regimen containing doravirine (DOR) with either TAF/FTC (or TAF/3TC), or the related medication tenofovir disoproxil fumarate/emtricitabine (TDF/FTC [or TDF/3TC]). DOR 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. In multiple studies, DOR was shown to be just as effective as INSTI medications for treating HIV.
Requirements to Enter Study (things that must be true for you):
- Living with HIV-1.
- Be ≥ 18 years old.
- Currently on an Integrase Inhibitor (INSTI) containing regimen (BIC, DTG or RAL), with > 48 weeks INSTI+TAF/FTC (or TAF/3TC) dosing prior to study entry.
- Have experienced > 10% weight gain in the 1-3 years after starting these medications.
- Have a body mass index (BMI) >5 kg/m2.
- Have study related tests done, including a DEXA Scan (X-Ray Scan measuring measure lean muscle, body fat and bone density).
- Agree to use contraception/birth control methods if capable of becoming pregnant.
- Be willing to change ART if randomized to Arms 1 or 2.
Exclusion Criteria (things that cannot be true about you):
- Recent serious illness or condition requiring hospitalization.
- Breastfeeding or pregnant.
- Historic or current evidence of resistance to the study medication or other medications in its class.
- Plans to undergo weight loss surgery or to start significant changes to your diet or exercise habits
Talk to your study staff for a complete list of inclusion/exclusion criteria.
When you enter this study, you will be randomized (assigned by chance, as if by roll of dice) to one of three study groups. Because the randomization is equal, you will have a 33% chance of being in any of the following study groups:
- Group 1: You will continue taking TAF/FTC (or TAF/3TC) but will stop your INSTI and take DOR; your ART will be DOR+TAF/FTC (or TAF/3TC) for 48 weeks.
- Group 2: You will stop your INSTI and TAF/FTC (or TAF/3TC) and will switch to DOR+TDF/FTC (or TDF/3TC) for 48 weeks.
- Group 3: You will continue your current ART of an INSTI+TAF/FTC (or TAF/3TC) for 48 weeks.
- Blood and urine tests at scheduled clinic visits for safety evaluations and other research testing.
- Questionnaires asking for information on adherence to ART and diet and exercise habits.
- DEXA Scan (Dual-Energy X-Ray Absorptiometry) to measure lean muscle, body fat and bone density.
Duration of Study: Almost 1 year (48 weeks). Follow-up visits will occur at Weeks 4, 12, 24, 36 and 48 (study completion).