NCT04636437

Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide

Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide (The Do IT Study)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 147 (actual)
• Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to determine if people with HIV and obesity taking an antiretroviral treatment regimen containing an integrase strand transfer inhibitor (INSTI) with (tenofovir alafenamide/emtricitabine (TAF/FTC) would either slow their rate of weight gain, or even lose weight, over the span of about 1 year after a switch to a regimen containing doravirine (DOR; a newer, non-nucleoside reverse transcriptase inhibitor medication) combined with either TAF/TFC or tenofovir disoproxil fumarate (TDF)/FTC.

Detailed description

The study evaluated whether a switch from an INSTI to a DOR-based regimen would result in less weight gain or weight loss at 48 weeks among obese individuals with HIV and a suppressed viral load. The study also evaluated whether an additional switch from TAF/FTC to TDF/FTC, both in combination with DOR, had an effect on weight over 48 weeks. Participants enrolled in A5391 were taking INSTI-class medications, including bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL), all in combination with TAF/FTC. Additionally, the study examined whether a change in the HIV treatment regimen affects other health indicators, including waist circumference, metabolic and cardiovascular disease markers, body composition (fat and lean mass), bone density, and maintenance of virologic suppression. Finally, the study looked at the safety and tolerability of DOR with either TAF/FTC or TDF/FTC. As originally designed, the trial's target population included individuals with an unintentional \>10% weight gain in the 1-3 years after initiating or switching to an INSTI-based treatment regimen. Due to not meeting accrual targets during the first year of enrollment (July 2021 - July 2022), the trial protocol was updated to amend the target population (and associated eligibility criteria) to individuals with obesity (a screening body mass index \[BMI\] of ≥30 kg/m2) irrespective of weight history on INSTI-based ART. This update was implemented on November 17, 2022, at which time 64 participants had enrolled under the original trial design. The remaining participants enrolled using the revised eligibility criterion. At a planned interim analysis in 2023, the method of blinded sample size re-estimation was used to assess if the trial's primary objective could be met with a sample size smaller than originally planned (n=222). Based on the pooled (e.g. over all arms) standard deviation of the primary outcome (weight change at 48 weeks), 150 participants would provide over 80% statistical power to detect the originally hypothesized 5% points change in weight between arms, assuming that this interim estimate was representative of the true variability about the primary outcome. As a result, the accrual goal was adjusted accordingly. The trial closed to enrollment in October 2024, having reached 147 participants.

Conditions

• HIV Infections

Interventions

Type	Name	Description
DRUG	Doravirine 100 Mg	Participants received a 100 mg tablet by mouth daily with or without food.
DRUG	Integrase strand transfer inhibitors	INSTIs were acquired through the standard of care locally.
DRUG	Tenofovir alafenamide/emtricitabine	NRTIs (TAF/FTC) were acquired through the standard of care locally.
DRUG	tenofovir disproxil fumarate/emtricitabine	NRTIs (TDF/FTC) were acquired through the standard of care locally.

Timeline

• Start date: 2021-07-27
• Primary completion: 2024-10-18
• Completion: 2024-10-18
• First posted: 2020-11-19
• Last updated: 2025-07-02
• Results posted: 2025-07-02

Locations

27 sites across 1 country: United States

Regulatory

• FDA-regulated drug study