A Phase 2 interventional study of Dolutegravir (DTG) AND Tenofovir alafenamide (TAF) and Tenofovir Disoproxil Fumarate in Healthy Volunteer, Weight Gain and Metabolic Effects, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Recruiting at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-29.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Basic science
Background:
People with HIV take drugs to keep the amount of virus in their body low. One type of these drugs, called integrase strand transfer inhibitors (INSTIs), can cause weight gain over time. Weight gain can cause diabetes, heart disease, and other serious issues. Researchers want to understand how INSTIs cause weight changes.
Objective:
To characterize the change in plasma metabolite profile that 4 weeks of each treatment may induce in the absence of HIV infection
Eligibility:
Healthy people aged 18 to 55.
Design:
Participants will be screened in the outpatient clinic. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function.
Participants will be randomized to one of four oral treatments: Tenofovir Disoproxil Fumarate TDF, Tenovovir Alafenamide TAF/Vemlidy, Dolutegravir DTG/Tivicay, or both TAF and DTG taken together for 4 weeks.
Participants will have a Day 0 visit for the Lead-In Baseline visit for an exam and blood tests and continuous glucose monitor placement.
Participants will return in 2wks or Day 14/Wk 2 for a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density. Optional adiopse (fat) tissue biopsy in the abdomen, and optional microbiome specimen collections. Continuous glucose monitor changed. Oral once a day dose medication will be started with education.
Participants will return in 2wks or Day 28/Wk 4 for exam, labs, and continuous glucose monitor changed.
Participants will return in 2wks or Day 42/Wk 6 for final exam, labs, repeat DEXA scan, repeat adipose tissue biopsy, and microbiome specimen collections.
Study Description:
Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral (ARV) drugs that are currently among first-line therapies to treat and prevent HIV. Several observational trials have shown that one side effect of this class of ARVs is involuntary weight gain. How these drugs cause weight gain is incompletely understood. In addition, one of these marketed drugs (bictegravir) is coformulated in combination with the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir alafenamide (TAF), which may also independently contribute to weight gain, including when it is compared against the related prodrug tenofovir disoproxil fumarate (TDF). To better understand the effects of INSTIs and TAF on metabolism, healthy volunteer participants will be randomized 1:1:1:1 to one of four arms: the INSTI dolutegravir (DTG), TAF, DTG plus TAF, or TDF. Participants will undergo an initial screening evaluation, a 2-week treatment-free lead-in period, and then a 4-week open-label treatment phase during which they will take the assigned study drug(s). During the study, participants will be assessed for changes in metabolic pathways, metabolites, and gene expression using a multi-omic approach. They will undergo serial research sample collection, including adipose tissue biopsy and microbiome sampling, both prior to initiation and after 4 weeks of the study drug(s).
Objectives:
Primary Objective:
To characterize the change in plasma metabolite profile that 4 weeks of each treatment may induce in the absence of HIV infection.
Secondary Objectives:
Exploratory Objectives:
Endpoints:
Primary Endpoint:
Change in plasma metabolites from ARV initiation to the end of the 4-week period of ARV therapy with each treatment.
Secondary Endpoints:
Exploratory Endpoints:
317 studies on the registry are indexed under Weight Gain; 48 are open to participants now.
This study's planned enrollment of 120 is above the median of 83 across 251 interventional studies indexed under Weight Gain.
Browse Weight Gain studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
Current use of the following prescription or over-the-counter medications and supplements:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
50mg one tablet orally once a day for 4 weeks, Day 14 to Day 42
Drug: Dolutegravir
50mg one tablet orally AND 25mg one tablet orally together once a day for 4 weeks, Day 14 to Day 42
Drug: Dolutegravir (DTG) AND Tenofovir alafenamide (TAF)
25mg one tablet orally once a day for 4 weeks, Day 14 to Day 42
Drug: Tenofovir alafenamide
300mg one tablet orally once daily for 4 weeks, Day 14 to Day 42
Drug: Tenofovir Disoproxil Fumarate
Drug pages: Dolutegravir · Tenofovir alafenamide
50mg dolutegravir (DTG) one tablet AND 25mg tenofovir alafenamide (TAF) one tablet together, orally once daily for 4 wks (Day 14 to Day 42)
300mg tenofovir disoproxil fumarate (TDF) one tablet orally once daily for 4 wks (Day 14 to Day 42)
50mg dolutegravir (DTG) one tablet orally once daily for 4 wks (Day 14 to Day 42)
25mg tenofovir alafenamide (TAF) one tablet orally once a day for 4 wks (Day 14 to Day 42)
Change in plasma metabolites from ARV initiation to the end of the 4 week period of ARV therapy with each treatment
To determine if TAF or DTG or TDF or DTG/TAF induce changes in plasma metabolites in the 4wks of therapy
Time frame: Day 14/Wk2 to Day 42/Wk6 of ARV therapy for each of 4 drug regimen.
Encompassing transcriptomic changes, metabolic alterations, lipidomic shifts, and proteomic variations.
To determine if TAF or DTG or TDF or DTG/TAF are associated with multi-omic profile changes in plasma, PBMCs, and adipose tissue
Time frame: Throughout study - Baseline to Day 42/Wk 6
Comprehensive multi-omic profile changes in plasma, PBMCs, and adipose tissue from ARV initiation to the end of the 4 week treatment period with each of four treatments
To determine if TAF or DTG or TDF or DTG/TAF are associated with multi-omic profile changes in plasma, PBMCs, and adipose tissue.
Time frame: Throughout study - Baseline to Day 42/Wk 6
Relationship between demographic data or baseline laboratory values and multi-omic profile changes in plasma, PBMC, and adipose tissue.
To determine if baseline demographic or laboratory characteristics are associated with multi-omic profile changes in plasma, PBMC, and adipose tissue.
Time frame: Throughout study - Baseline to Day 42/Wk 6
Multi-omic comparisons between DTG and/or TAF versus TDF.
To compare multi-omic profile changes between DTG, or DTG plus TAF, or TAF, versus TDF.
Time frame: Throughout study - Baseline to Day 42/Wk 6
Plan to share: No — We have no plans to share data with anyone outside of the study team
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Dolutegravir · Tenofovir alafenamide · Tenofovir
National Institute of Allergy and Infectious Diseases (NIAID) →