HIV InfectionsPhase 4NCT04636437
Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide
A Phase 4 study testing Doravirine 100 Mg, Integrase strand transfer inhibitors and Tenofovir alafenamide/emtricitabine in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 27 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Doravirine 100 Mg, Integrase strand transfer inhibitors and Tenofovir alafenamide/emtricitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 147 participants
- Where
- 27 sitesUnited States
- Study dates
- 27 Jul 2021to 18 Oct 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability and willingness of participant or legal guardian/representative to provide informed consent.
- HIV-1, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load. If a rapid HIV test or any FDA-approved HIV-1 E/CIA test kit is not available, two HIV-1 RNA values ≥2000 copies/mL at least 24 hours apart may be performed by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or by any non-US laboratory that is DAIDS Good Clinical Laboratory Practice (GCLP) compliant and, if performing HIV-1 RNA testing, is Virology Quality Assurance (VQA)-certified.
- Currently on a bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL) + TAF/FTC regimen with ≥48 weeks prior to study entry.
- Ability to acquire NRTIs (TAF/FTC or TDF/FTC) and INSTI through usual care for the duration of the study.
- A BMI ≥30 kg/m2 at screening. No known plans to change or to initiate medications known to be associated with significant weight changes during study period.
- Agree to adhere to assigned ART during the study period At least one HIV-1 RNA level <50 copies/mL (or below the lower limit of HIV-1 RNA detection available at the site if the lower limit of detection is >50) performed in the 48 weeks prior (≤48 weeks) to study screening, and at least one HIV-1 RNA level <50 copies/mL ≥48 weeks prior to study screening, using an FDA-approved assay performed by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that is VQA certified.
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- Screening HIV-1 RNA <50 copies/mL (or below the lower limit of HIV-1 RNA detection available if the lower limit of detection is >50) performed within 45 days prior to study entry by any US laboratory that possesses a CLIA certification or its equivalent, or at any network-approved non-US laboratory that is VQA certified.
- For participants capable of becoming pregnant, negative serum or urine pregnancy test within 45 days prior to study entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/ CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.
- Participants engaging in sexual activity and capable of becoming pregnant must agree to use contraception while on study drug (approximately 48 weeks) and for 8 weeks after the end of the study. At least one of the following contraceptive methods must be used:
- Intrauterine device (IUD)
- Hormone-based contraceptive
- Partner sterilization (i.e., vasectomy) and is the sole partner for the participant.
- Transgender participants who are currently taking hormones must be on a stable hormone dose for >12 weeks prior to study entry. Transgender participants should not have active plans to change their hormone regimen or dose during the study period.
- The following laboratory values obtained within 45 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs:
- Absolute neutrophil count (ANC) >750 cells/mm3
- Hemoglobin >10 g/dL for males and >9 g/dL for females (based on sex at birth)
- Calculated creatinine clearance ≥50 mL/min as estimated by the CKD-EPI equation (a calculator is available at: https://qxmd.com/calculate/calculator_251/egfr-using-ckd-epi)
- Aspartate aminotransferase (AST) (SGOT) <3x ULN
- Alanine aminotransferase (ALT) (SGPT) <3x ULN
Who cannot join
- Historical or current evidence of the K65R/E/N or M184V/I mutations (for participants who have undergone HIV-1 genotyping), due to the potential for viral rebound after switch from an INSTI- to NNRTI-based regimen.
- Historical or current evidence of major mutations associated with NNRTI resistance.
- History of prior virologic failure in the opinion of the site investigator. For example, a confirmed plasma HIV-1 RNA >1000 copies/mL after having achieved viral suppression.
- Prior exposure to single-dose nevirapine for the prevention of parent-to-child transmission of HIV.
- Any history of significant renal toxicity while taking TDF (as determined by the site investigator).
- Currently breast-feeding or pregnant, or intending to become pregnant during the duration of the study.
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- Current use, use in the 4 weeks preceding study entry, or anticipated use of prohibited drugs during the study period.
- Anticipated start or cessation of any of the following drugs during the study period:
- Antipsychotics (e.g., clozapine, olanzapine, risperidone, etc.) and antidepressants (tricyclic antidepressants, e.g., amitriptyline, nortriptyline, etc.; selective serotonin reuptake inhibitors, e.g., fluoxetine, paroxetine, sertraline, etc.; and monoamine oxidase inhibitors, e.g., selegiline) associated with weight gain
- Anticonvulsants/mood stabilizers associated with weight gain (e.g., lithium, valproic acid) or weight loss (e.g., topiramate)
- Thyroid replacement hormones
- Anti-diabetic agents known to cause weight loss (e.g., GLP-1 receptor agonists such as exenatide, dulaglutide, semaglutide, metformin, and SGLT-2 inhibitors such as canagliflozin, dapagliflozin, etc.).
- Planning to undergo bariatric surgery or initiate significant dietary or exercise changes within the study period (e.g., structured weight loss programs such as Weight Watchers), as determined by participant report.
- Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with ability to adhere to study requirements, or cessation of regular methamphetamine use, as determined by the site investigator, within 60 days prior to study entry.
- Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.
- A history of a diagnosis of osteoporosis or osteopenia.
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
United States27 sites
The Ponce de Leon Center CRS (5802)
Atlanta, Georgia, 30308
University of Colorado Hospital CRS (6101)
Aurora, Colorado, 80045
Johns Hopkins University CRS (201)
Baltimore, Maryland, 21205
Alabama CRS (31788)
Birmingham, Alabama, 35294
Massachusetts General Hospital (MGH) CRS (101)
Boston, Massachusetts, 02114
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, 02115
Chapel Hill CRS (3201)
Chapel Hill, North Carolina, 27514
Northwestern University CRS (2701)
Chicago, Illinois, 60611
Cincinnati CRS (2401)
Cincinnati, Ohio, 45267
Case CRS (2501)
Cleveland, Ohio, 44106
Ohio State University CRS (2301)
Columbus, Ohio, 43210
Greensboro CRS (3203)
Greensboro, North Carolina, 27401
Houston AIDS Research Team CRS (31473)
Houston, Texas, 77030
UCLA CARE Center CRS (601)
Los Angeles, California, 90095
Vanderbilt Therapeutics (VT) CRS (3652)
Nashville, Tennessee, 37204
Weill Cornell Chelsea CRS (7804)
New York, New York, 10010
Columbia Physicians and Surgeons (P&S) CRS (30329)
New York, New York, 10032
Weill Cornell Upton CRS (7803)
New York, New York, 10065
New Jersey Medical School Clinical Research Center CRS (31786)
Newark, New Jersey, 07103
Penn Therapeutics CRS (6201)
Philadelphia, Pennsylvania, 19104
University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)
Rochester, New York, 14642
UCSD Antiviral Research Center CRS (701)
San Diego, California, 92103
Ucsf Hiv/Aids Crs (801)
San Francisco, California, 94110
University of Washington Positive Research CRS (1401)
Seattle, Washington, 98104
Washington University Therapeutics (WT) CRS (2101)
St Louis, Missouri, 63110
Harbor-UCLA CRS (603)
Torrance, California, 90502
Whitman-Walker Institute, Inc. CRS (31791)
Washington D.C., District of Columbia, 20005
About this study
Official title: Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide (The Do IT Study)
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.
Read the 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
- Being tested
- Doravirine 100 Mg, Integrase strand transfer inhibitors, Tenofovir alafenamide/emtricitabine, tenofovir disproxil fumarate/emtricitabine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doravirine 100 MgDrug
Also called DOR
Participants received a 100 mg tablet by mouth daily with or without food.
Integrase strand transfer inhibitorsDrug
Also called INSTI
INSTIs were acquired through the standard of care locally.
Tenofovir alafenamide/emtricitabineDrug
Also called TAF, FTC
NRTIs (TAF/FTC) were acquired through the standard of care locally.
tenofovir disproxil fumarate/emtricitabineDrug
Also called TDF, FTC
NRTIs (TDF/FTC) were acquired through the standard of care locally.
| Study group | Role | What they receive |
|---|---|---|
| DOR 100 mg + TAF/FTC | Experimental | By mouth daily with or without food Receives: Drug: Doravirine 100 Mg; Drug: Integrase strand transfer inhibitors |
| DOR 100 mg + TDF/FTC | Experimental | By mouth daily with or without food Receives: Drug: Doravirine 100 Mg; Drug: tenofovir disproxil fumarate/emtricitabine |
| Continuation of INSTI+TAF/FTC | Active comparator | By mouth daily with or without food Receives: Drug: Integrase strand transfer inhibitors; Drug: Tenofovir alafenamide/emtricitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change (Percent) in Body Weight (kg) From Entry to Week 48
The percentage change is defined as weight at week 48 minus weight at entry, then divided by weight at entry, then multiplied by 100.
Mean and confidence interval (CI) come from a linear regression model adjusting for entry weight, sex, and race (Black and not Black).
Measured: Entry to week 48
Secondary outcomes (26)
Mean Change (Percent) in Body Weight (kg) From Entry to Week 24
The percentage change is defined as weight at week 24 minus weight at entry, then divided by weight at entry, then multiplied by 100.
Mean and CI come from a linear regression model adjusting for entry weight, sex, and race (Black and not Black).
Measured: Entry to week 24
Mean Change (Absolute) in Waist Circumference From Entry to Week 48
The absolute change is defined as waist circumference at week 48 minus waist circumference at entry.
Mean and CI come from a linear regression model adjusting for entry waist circumference, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Absolute) in Waist Circumference From Entry to Week 24
The absolute change is defined as waist circumference at week 24 minus waist circumference at entry.
Mean and CI come from a linear regression model adjusting for entry waist circumference, sex, and race (Black and not Black).
Measured: Entry to week 24
Mean Change (Absolute) in Fasting Triglycerides From Entry to Week 48
The absolute change is defined as triglycerides at week 48 minus triglycerides at entry.
Mean and CI come from a linear regression model adjusting for entry triglycerides, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Absolute) in Fasting Triglycerides From Entry to Week 24
The absolute change is defined as triglycerides at week 24minus triglycerides at entry.
Mean and CI come from a linear regression model adjusting for entry triglycerides, sex, and race (Black and not Black).
Measured: Entry to week 24
Mean Change (Absolute) in Fasting Low-density Lipoprotein (LDL) Cholesterol From Entry to Week 48
The absolute change is defined as LDL at week 48 minus LDL at entry. Mean and CI come from a linear regression model adjusting for entry LDL, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Absolute) in Fasting Low-density Lipoprotein (LDL) Cholesterol From Entry to Week 24
The absolute change is defined as LDL at week 24 minus LDL at entry. Mean and CI come from a linear regression model adjusting for entry LDL, sex, and race (Black and not Black).
Measured: Entry to week 24
Mean Change (Absolute) in Fasting High-density Lipoprotein (HDL) Cholesterol From Entry to Week 48
The absolute change is defined as HDL at week 48 minus HDL at entry. Mean and CI come from a linear regression model adjusting for entry HDL, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Absolute) in Fasting High-density Lipoprotein (HDL) Cholesterol From Entry to Week 24
The absolute change is defined as HDL at week 24 minus HDL at entry. Mean and CI come from a linear regression model adjusting for entry HDL, sex, and race (Black and not Black).
Measured: Entry to week 24
Mean Change (Absolute) in Fasting Glucose From Entry to Week 48
The absolute change is defined as glucose at week 48 minus glucose at entry. Mean and CI come from a linear regression model adjusting for entry glucose, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Absolute) in Fasting Glucose From Entry to Week 24
The absolute change is defined as glucose at week 24 minus glucose at entry. Mean and CI come from a linear regression model adjusting for entry glucose, sex, and race (Black and not Black).
Measured: Entry to week 24
Mean Change (Absolute) in Fasting Insulin From Entry to Week 48
The absolute change is defined as insulin at week 48 minus insulin at entry. Mean and CI come from a linear regression model adjusting for entry insulin, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Absolute) in Fasting Insulin From Entry to Week 24
The absolute change is defined as insulin at week 24 minus insulin at entry. Mean and CI come from a linear regression model adjusting for entry insulin, sex, and race (Black and not Black).
Measured: Entry to week 24
Mean Change (Absolute) in Insulin Resistance (HOMA-IR) From Entry to Week 48
The absolute change is defined as HOMA-IR at week 48 minus HOMA-IR at entry. HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) is a method used to estimate how well the body responds to insulin and is calculated with the following formula: (Fasting insulin, μU/ml)*(Fasting glucose, mg/dL) / 405 Mean and CI come from a linear regression model adjusting for entry HOMA-IR, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Absolute) in Insulin Resistance (HOMA-IR) From Entry to Week 24
The absolute change is defined as HOMA-IR at week 24 minus HOMA-IR at entry. HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) is a method used to estimate how well the body responds to insulin and is calculated with the following formula: (Fasting insulin, μU/ml)*(Fasting glucose, mg/dL) / 405 Mean and CI come from a linear regression model adjusting for entry HOMA-IR, sex, and race (Black and not Black).
Measured: Entry to week 24
Number of Participants With Confirmed Plasma HIV-1 RNA >200 Copies/mL
Number of participants with confirmed plasma HIV-1 RNA >200 copies/mL, defined as two consecutive results above 200 copies, with the drawing of the second specimen within 2 weeks of site receipt of the first result, and the first result being from a specimen drawn after treatment initiation.
Measured: Entry through week 48
Proportion of Participants With Grade ≥3 AEs From Entry to Week 48
Proportion of participants with Grade ≥3 AEs Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death.
Measured: Entry to week 48
Proportion of Participants With >10% Reduction in Creatinine Clearance (CrCl) From Entry to Week 48
CrCl was estimated by the 2021 CKD-EPI equation and was measured at entry, week 4, week 12, week 24, and week 48.
The percentage change is defined as CrCl at an on study visit minus CrCl at entry, then divided by CrCl at entry, then multiplied by 100.
Participants were categorized as experiencing a >10% reduction in CrCl if they experienced the >10% reduction at any of the study visits (week 4, week 12, week 24, and week 48).
Measured: Entry to week 48
Proportion of Participants With Premature Discontinuation of Study Treatment
Proportion of participants who permanently discontinued any component of study treatment prior to completion of a week 48 visit following randomization
Measured: Entry to week 48
Mean Change (Percent) in Total Fat (kg) From Entry to Week 48
Total fat was measured by DEXA (dual-energy x-ray absorptiometry) scan. The percentage change is defined as total fat at week 48 minus total fat at entry, then divided by total fat at entry, then multiplied by 100.
Mean and CI come from a linear regression model adjusting for entry total fat, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Percent) in Lean Mass (kg) From Entry to Week 48
Lean mass was measured by DEXA (dual-energy x-ray absorptiometry) scan. The percentage change is defined as lean mass at week 48 minus lean mass at entry, then divided by lean mass at entry, then multiplied by 100.
Mean and CI come from a linear regression model adjusting for entry lean mass, sex, and race (Black and not Black).
Measured: Day 0 to week 48
Mean Change (Percent) in Trunk Fat (kg) From Entry to Week 48
Trunk fat was measured by DEXA (dual-energy x-ray absorptiometry) scan. The percentage change is defined as trunk fat at week 48 minus trunk fat at entry, then divided by trunk fat at entry, then multiplied by 100.
Mean and CI come from a linear regression model adjusting for entry trunk fat, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Percent) in Limb Fat (kg) From Entry to Week 48
Limb fat was measured by DEXA (dual-energy x-ray absorptiometry) scan. The percentage change is defined as limb fat at week 48 minus limb fat at entry, then divided by limb fat at entry, then multiplied by 100.
Mean and CI come from a linear regression model adjusting for entry total fat, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Percent) in Appendicular Lean Mass (kg) From Entry to Week 48
Appendicular lean mass was measured by DEXA (dual-energy x-ray absorptiometry) scan.
The percentage change is defined as appendicular lean mass at week 48 minus appendicular lean mass at entry, then divided by appendicular lean mass at entry, then multiplied by 100.
Mean and CI come from a linear regression model adjusting for entry appendicular lean mass, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Percent) in Hip Bone Mineral Density (g/cm2) From Entry to Week 48
Hip bone mineral density was measured by DEXA (dual-energy x-ray absorptiometry) scan.
The percentage change is defined as hip bone mineral density at week 48 minus hip bone mineral density at entry, then divided by hip bone mineral density at entry, then multiplied by 100.
Mean and CI come from a linear regression model adjusting for entry hip bone mineral density, sex, and race (Black and not Black).
Measured: Entry to week 48
Mean Change (Percent) in Lumbar Spine Bone Mineral Density (g/cm2) From Entry to Week 48
Lumbar spine bone mineral density was measured by DEXA (dual-energy x-ray absorptiometry) scan.
The percentage change is defined as lumbar spine bone mineral density at week 48 minus lumbar spine bone mineral density at entry, then divided by lumbar spine bone mineral density at entry, then multiplied by 100.
Mean and CI come from a linear regression model adjusting for entry lumbar spine bone mineral density, sex, and race (Black and not Black).
Measured: Entry to week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2020
- Study start27 Jul 2021
- Primary completion18 Oct 2024
- Study completion18 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- John Koethe, Study chair, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04636437
- Sponsor's protocol ID
- ACTG A5391
- Other IDs
- UM1AI068636
- Status last verified
- Jun 2025
- First submitted
- 13 Nov 2020
- Last updated
- 2 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.
Publications
Koethe JR, Lake JE, Kantor A, Smeaton L, Erlandson K, Moran L, Belaunzaran-Zamudio P, Landay A, Campo RE, Debroy P, Bennet JA, O'Halloran J, Han WM, Alli O, Leonard M, Gulick RM. A 48-Week, Randomized Controlled Trial of Doravirine for Individuals With HIV and Obesity on Integrase Inhibitors and Tenofovir Alafenamide: The Do IT Study (ACTG A5391). Clin Infect Dis. 2026 Jul 23;83(1):e81-e89. doi: 10.1093/cid/ciag196.
PubMed 41847923
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide (The Do IT Study)
- ClinicalTrials.gov ID
- NCT04636437
- Acronym / sponsor ID
- ACTG A5391
- Conditions
- HIV Infections
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 27 Jul 2021 (actual)
- Primary completion
- 18 Oct 2024 (actual)
- Study completion
- 18 Oct 2024 (actual)
- First posted
- 19 Nov 2020 (actual)
- Results
- Posted 2 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DOR 100 mg + TAF/FTC | Experimental | Drug: Doravirine 100 Mg, Drug: Integrase strand transfer inhibitorsBy mouth daily with or without food |
| DOR 100 mg + TDF/FTC | Experimental | Drug: Doravirine 100 Mg, Drug: tenofovir disproxil fumarate/emtricitabineBy mouth daily with or without food |
| Continuation of INSTI+TAF/FTC | Active comparator | Drug: Integrase strand transfer inhibitors, Drug: Tenofovir alafenamide/emtricitabineBy mouth daily with or without food |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Ability and willingness of participant or legal guardian/representative to provide informed consent.
- HIV-1, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load. If a rapid HIV test or any FDA-approved HIV-1 E/CIA test kit is not available, two HIV-1 RNA values ≥2000 copies/mL at least 24 hours apart may be performed by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or by any non-US laboratory that is DAIDS Good Clinical Laboratory Practice (GCLP) compliant and, if performing HIV-1 RNA testing, is Virology Quality Assurance (VQA)-certified.
- Currently on a bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL) + TAF/FTC regimen with ≥48 weeks prior to study entry.
- Ability to acquire NRTIs (TAF/FTC or TDF/FTC) and INSTI through usual care for the duration of the study.
- A BMI ≥30 kg/m2 at screening. No known plans to change or to initiate medications known to be associated with significant weight changes during study period.
Key exclusion criteria (17 listed)
- Historical or current evidence of the K65R/E/N or M184V/I mutations (for participants who have undergone HIV-1 genotyping), due to the potential for viral rebound after switch from an INSTI- to NNRTI-based regimen.
- Historical or current evidence of major mutations associated with NNRTI resistance.
- History of prior virologic failure in the opinion of the site investigator. For example, a confirmed plasma HIV-1 RNA >1000 copies/mL after having achieved viral suppression.
- Prior exposure to single-dose nevirapine for the prevention of parent-to-child transmission of HIV.
- Any history of significant renal toxicity while taking TDF (as determined by the site investigator).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doravirine 100 MgAlso: DORParticipants received a 100 mg tablet by mouth daily with or without food. | Drug | DOR 100 mg + TAF/FTC, DOR 100 mg + TDF/FTC |
| Integrase strand transfer inhibitorsAlso: INSTIINSTIs were acquired through the standard of care locally. | Drug | Continuation of INSTI+TAF/FTC, DOR 100 mg + TAF/FTC |
| Tenofovir alafenamide/emtricitabineAlso: TAF, FTCNRTIs (TAF/FTC) were acquired through the standard of care locally. | Drug | Continuation of INSTI+TAF/FTC |
| tenofovir disproxil fumarate/emtricitabineAlso: TDF, FTCNRTIs (TDF/FTC) were acquired through the standard of care locally. | Drug | DOR 100 mg + TDF/FTC |
Primary outcome
Mean Change (Percent) in Body Weight (kg) From Entry to Week 48
Time frame: Entry to week 48
The percentage change is defined as weight at week 48 minus weight at entry, then divided by weight at entry, then multiplied by 100. Mean and confidence interval (CI) come from a linear regression model adjusting for entry weight, sex, and race (Black and not Black).
26 secondary outcomes
Mean Change (Percent) in Body Weight (kg) From Entry to Week 24
Time frame: Entry to week 24
Mean Change (Absolute) in Waist Circumference From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Absolute) in Waist Circumference From Entry to Week 24
Time frame: Entry to week 24
Mean Change (Absolute) in Fasting Triglycerides From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Absolute) in Fasting Triglycerides From Entry to Week 24
Time frame: Entry to week 24
Mean Change (Absolute) in Fasting Low-density Lipoprotein (LDL) Cholesterol From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Absolute) in Fasting Low-density Lipoprotein (LDL) Cholesterol From Entry to Week 24
Time frame: Entry to week 24
Mean Change (Absolute) in Fasting High-density Lipoprotein (HDL) Cholesterol From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Absolute) in Fasting High-density Lipoprotein (HDL) Cholesterol From Entry to Week 24
Time frame: Entry to week 24
Mean Change (Absolute) in Fasting Glucose From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Absolute) in Fasting Glucose From Entry to Week 24
Time frame: Entry to week 24
Mean Change (Absolute) in Fasting Insulin From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Absolute) in Fasting Insulin From Entry to Week 24
Time frame: Entry to week 24
Mean Change (Absolute) in Insulin Resistance (HOMA-IR) From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Absolute) in Insulin Resistance (HOMA-IR) From Entry to Week 24
Time frame: Entry to week 24
Number of Participants With Confirmed Plasma HIV-1 RNA >200 Copies/mL
Time frame: Entry through week 48
Proportion of Participants With Grade ≥3 AEs From Entry to Week 48
Time frame: Entry to week 48
Proportion of Participants With >10% Reduction in Creatinine Clearance (CrCl) From Entry to Week 48
Time frame: Entry to week 48
Proportion of Participants With Premature Discontinuation of Study Treatment
Time frame: Entry to week 48
Mean Change (Percent) in Total Fat (kg) From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Percent) in Lean Mass (kg) From Entry to Week 48
Time frame: Day 0 to week 48
Mean Change (Percent) in Trunk Fat (kg) From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Percent) in Limb Fat (kg) From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Percent) in Appendicular Lean Mass (kg) From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Percent) in Hip Bone Mineral Density (g/cm2) From Entry to Week 48
Time frame: Entry to week 48
Mean Change (Percent) in Lumbar Spine Bone Mineral Density (g/cm2) From Entry to Week 48
Time frame: Entry to week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41847923Koethe JR, Lake JE, Kantor A, Smeaton L, Erlandson K, Moran L, Belaunzaran-Zamudio P, Landay A, Campo RE, Debroy P, Bennet JA, O'Halloran J, Han WM, Alli O, Leonard M, Gulick RM. A 48-Week, Randomized Controlled Trial of Doravirine for Individuals With HIV and Obesity on Integrase Inhibitors and Tenofovir Alafenamide: The Do IT Study (ACTG A5391). Clin Infect Dis. 2026 Jul 23;83(1):e81-e89. doi: 10.1093/cid/ciag196.
- Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017)Link provided by the sponsor.
- Manual for Expedited Reporting of Adverse Events to DAIDS (Version 2.0 - January 2010)Link provided by the sponsor.
- CKD-EPI Creatinine Equation (2021)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie results in the publication, after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Koethe study chair
Vanderbilt University Medical Center
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doravirine 100 Mg, Integrase strand transfer inhibitors and Tenofovir alafenamide/emtricitabine in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 27 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change (Percent) in Body Weight (kg) From Entry to Week 48 (time frame: Entry to week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04636437, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2025.