Healthy VolunteerPhase 2NCT05652478
Early Metabolic Effects of Antiretroviral Drugs in Healthy volUnteers: a Phase 2 Randomized Study
A Phase 2 study testing Dolutegravir (DTG) AND Tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate and Dolutegravir in people with Healthy Volunteer and Weight Gain, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer, Weight Gain, Metabolic Effects
- What is being tested?
- Dolutegravir (DTG) AND Tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate and Dolutegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Sep 2026to 31 Jan 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Aged 18 to 55 years.
- Able to provide informed consent.
- Willing to allow samples and data to be stored and shared for future research.
- Agrees to use a barrier method of contraception or abstain from sexual activity starting at screening though the end of study participation.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Current infection with HIV or hepatitis A, B, or C.
- Body mass index (BMI) <18.5 kg/m^2 or >30.0 kg/m^2.
- Weight change >5% in the past 6 months.
- History of or current cardiovascular disease such as congestive heart failure, heart block, or clinically relevant abnormal ECG as determined by investigators.
- History of or current liver disease or alanine transaminase serum level >2x upper limit of normal.
Show all 48Show fewer
- History of or current kidney disease or renal insufficiency, or estimated creatinine clearance <=80 mL/min (Modification of Diet in Renal Disease equation).
- Current cancer or history of cancer within 5 years of screening, with the exception of squamous cell carcinoma or basal cell carcinoma that is localized and does not require systemic therapy.
- History of bariatric surgery.
- Diabetes mellitus as defined by a prior diagnosis or a hemoglobin A1c of >6.4 percent on screening labs.
- Fasting serum glucose >126 mg/dL.
- History of or current hypo- or hyper-thyroid or abnormal TSH, except minor deviations deemed to be of no clinical significance by the investigator.
- History of chronic obstructive pulmonary disease.
- Psychological conditions by self-report, such as (but not limited to) clinical depression, or bipolar disorders, which would be incompatible with safe and successful participation in this study.
- Pregnancy or within 1 year post-partum.
- Breastfeeding.
- Blood pressure >140/90 mm Hg or current antihypertensive therapy.
- Hemoglobin that is either 10 percent below the lower limit or 10 percent above the upper limit of the normal range for the Clinical Center Laboratory (acceptable ranges: females 10.08-17.27 g/dL, males 12.33-19.25 g/dL).
- History of illicit drug, opioid, or alcohol abuse within the last 5 years; current use of illicit drugs or opioids (by history) or excessive alcohol (CAGE assessment score >=2).
- Current use of the following prescription or over-the-counter medications and supplements:
- Carbamazepine
- Oxcarbazepine
- Phenobarbital
- Phenytoin
- Primidone
- Rifabutin
- Rifampin
- Rifapentine
- St. John's wort (Hypericum perforatum)
- Cation-containing antacids or laxatives
- Sucralfate
- Buffered medications
- Oral calcium, iron, magnesium, or zinc supplements, including multivitamins containing these polyvalent cations
- Dalfampridine
- Metformin
- Dofetilide
- Thyroid medications
- Corticosteroids
- Weight loss medications, including prescription drugs (eg, semaglutide and tirzepatide) and over-the-counter diet pills
- Use of TAF, TDF, and/or FTC for the purpose of HIV PrEP or in a research study within the past 6 months.
- Any history of exposure to cabotegravir or lenacapavir (eg, as HIV PrEP or as a participant in a research study for these drugs).
- Current use of prescription or nonprescriptive medications that may have interactions with study drugs or confound the study measurements as determined by the investigators.
- History of adverse or allergic reactions to the study drugs.
- Daily caffeine intake >500 mg (about 4 cups of coffee).
- Current smoker or user of tobacco products.
- A change in the participant's diet and/or exercise regimen in the past 3 months or during the timeframe of the study period that, in the opinion of the investigator, would compromise the integrity of the data.
- High-risk sexual activity as determined by the investigators, and/or inability or unwillingness to use barrier contraception during the protocol.
- Any other condition, medication, or dietary pattern that, in the opinion of the investigators, increases risk to the participant, prevents the participant from complying with study procedures, prevents the participant from completing the study, or interferes with the interpretation of study results.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Early Metabolic Effects of Antiretroviral Drugs in Healthy Volunteers: A Phase 2 Randomized Study
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.
Read more
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.
Read the detailed description
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:
- To characterize the change in plasma proteomics and lipidomics that 4 weeks of each treatment may induce in the absence of HIV infection.
- To characterize the change in peripheral blood mononuclear cell (PBMC) transcriptomics and cell populations that 4 weeks of each treatment may induce in the absence of HIV infection.
- To characterize the changes in adipose tissue via RNA sequencing, metabolomics, and proteomics that 4 weeks of each treatment may induce in the absence of HIV infection.
- To determine if baseline (prior to study agent administration) demographics (eg, age, sex, or weight) or laboratory characteristics (eg, free thyroxine [T4], thyroid-stimulating hormone [TSH], cortisol, or other hormones) are associated with multi-omic changes induced by each treatment.
- To compare the multi-omic changes induced by DTG and/or TAF versus TDF in the absence of HIV infection.
Exploratory Objectives:
- To determine if there is a correlation between pharmacokinetic (PK) measurements of TAF, DTG, or TDF and multi-omic changes.
- Evaluation of microbiota in vaginal, oral, and rectal mucosa, including potential reactivation of human endogenous retroviruses (HERVs) at start and the end of each treatment.
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:
- 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 treatment, encompassing transcriptomic changes, metabolomic alterations, lipidomic shifts, and proteomic variations.
- Relationship between demographic data or baseline laboratory values and multi-omic profile changes in plasma, PBMC, and adipose tissue.
- Multi-omic comparisons between DTG and/or TAF versus TDF.
Exploratory Endpoints:
- Relationship between PK parameters for TAF, DTG, and TDF and multi-omic profile changes in plasma, PBMC, and adipose tissue.
- Potential changes in microbiome composition and HERV reactivation after treatment periods.
- Being tested
- Dolutegravir (DTG) AND Tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate, Dolutegravir, Tenofovir alafenamide
- Keywords
- Metabolism, HIV, Integrase Strand Transfer Inhibitors
- Medical subject headings
- Weight Gain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dolutegravir (DTG) AND Tenofovir alafenamide (TAF)Drug
50mg dolutegravir (DTG) one tablet AND 25mg tenofovir alafenamide (TAF) one tablet together, orally once daily for 4 wks (Day 14 to Day 42)
Tenofovir Disoproxil FumarateDrug
300mg tenofovir disoproxil fumarate (TDF) one tablet orally once daily for 4 wks (Day 14 to Day 42)
DolutegravirDrug
50mg dolutegravir (DTG) one tablet orally once daily for 4 wks (Day 14 to Day 42)
Tenofovir alafenamideDrug
25mg tenofovir alafenamide (TAF) one tablet orally once a day for 4 wks (Day 14 to Day 42)
| Study group | Role | What they receive |
|---|---|---|
| Dolutegravir | Active comparator | 50mg one tablet orally once a day for 4 weeks, Day 14 to Day 42 Receives: Drug: Dolutegravir |
| Dolutegravir AND Tenofovir alafenamide | Active comparator | 50mg one tablet orally AND 25mg one tablet orally together once a day for 4 weeks, Day 14 to Day 42 Receives: Drug: Dolutegravir (DTG) AND Tenofovir alafenamide (TAF) |
| Tenofovir alafenamide | Active comparator | 25mg one tablet orally once a day for 4 weeks, Day 14 to Day 42 Receives: Drug: Tenofovir alafenamide |
| Tenofovir Disoproxil Fumarate | Active comparator | 300mg one tablet orally once daily for 4 weeks, Day 14 to Day 42 Receives: Drug: Tenofovir Disoproxil Fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 14/Wk2 to Day 42/Wk6 of ARV therapy for each of 4 drug regimen.
Secondary outcomes (4)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Throughout study - Baseline to Day 42/Wk 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2022
- Study start24 Sep 2026
- Primary completion31 Jan 2028 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Brian P Epling, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05652478
- Sponsor's protocol ID
- 10000906
- Other IDs
- 000906-I
- Status last verified
- 9 Sep 2026
- First submitted
- 10 Dec 2022
- Last updated
- 29 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We have no plans to share data with anyone outside of the study team
Publications
Squires K, Kityo C, Hodder S, Johnson M, Voronin E, Hagins D, Avihingsanon A, Koenig E, Jiang S, White K, Cheng A, Szwarcberg J, Cao H. Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. Lancet HIV. 2016 Sep;3(9):e410-e420. doi: 10.1016/S2352-3018(16)30016-9. Epub 2016 May 27.
PubMed 27562742Molina JM, Clotet B, van Lunzen J, Lazzarin A, Cavassini M, Henry K, Kulagin V, Givens N, de Oliveira CF, Brennan C; FLAMINGO study team. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. 2015 Apr;2(4):e127-36. doi: 10.1016/S2352-3018(15)00027-2. Epub 2015 Mar 10.
PubMed 26424673Lennox JL, Landovitz RJ, Ribaudo HJ, Ofotokun I, Na LH, Godfrey C, Kuritzkes DR, Sagar M, Brown TT, Cohn SE, McComsey GA, Aweeka F, Fichtenbaum CJ, Presti RM, Koletar SL, Haas DW, Patterson KB, Benson CA, Baugh BP, Leavitt RY, Rooney JF, Seekins D, Currier JS; ACTG A5257 Team. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014 Oct 7;161(7):461-71. doi: 10.7326/M14-1084.
PubMed 25285539
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Metabolic Effects of Antiretroviral Drugs in Healthy Volunteers: A Phase 2 Randomized Study
- ClinicalTrials.gov ID
- NCT05652478
- Acronym / sponsor ID
- 10000906
- Keywords
- Metabolism, HIV, Integrase Strand Transfer Inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 24 Sep 2026 (actual)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 31 Jan 2030 (estimated)
- First posted
- 15 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- To characterize the change in plasma proteomics and lipidomics that 4 weeks of each treatment may induce in the absence of HIV infection.
- To characterize the change in peripheral blood mononuclear cell (PBMC) transcriptomics and cell populations that 4 weeks of each treatment may induce in the absence of HIV infection.
- To characterize the changes in adipose tissue via RNA sequencing, metabolomics, and proteomics that 4 weeks of each treatment may induce in the absence of HIV infection.
- To determine if baseline (prior to study agent administration) demographics (eg, age, sex, or weight) or laboratory characteristics (eg, free thyroxine [T4], thyroid-stimulating hormone [TSH], cortisol, or other hormones) are associated with multi-omic changes induced by each treatment.
- To compare the multi-omic changes induced by DTG and/or TAF versus TDF in the absence of HIV infection.
Exploratory Objectives:
- To determine if there is a correlation between pharmacokinetic (PK) measurements of TAF, DTG, or TDF and multi-omic changes.
- Evaluation of microbiota in vaginal, oral, and rectal mucosa, including potential reactivation of human endogenous retroviruses (HERVs) at start and the end of each treatment.
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:
- 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 treatment, encompassing transcriptomic changes, metabolomic alterations, lipidomic shifts, and proteomic variations.
- Relationship between demographic data or baseline laboratory values and multi-omic profile changes in plasma, PBMC, and adipose tissue.
- Multi-omic comparisons between DTG and/or TAF versus TDF.
Exploratory Endpoints:
- Relationship between PK parameters for TAF, DTG, and TDF and multi-omic profile changes in plasma, PBMC, and adipose tissue.
- Potential changes in microbiome composition and HERV reactivation after treatment periods.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dolutegravir | Active comparator | Drug: Dolutegravir50mg one tablet orally once a day for 4 weeks, Day 14 to Day 42 |
| Dolutegravir AND Tenofovir alafenamide | Active comparator | Drug: Dolutegravir (DTG) AND Tenofovir alafenamide (TAF)50mg one tablet orally AND 25mg one tablet orally together once a day for 4 weeks, Day 14 to Day 42 |
| Tenofovir alafenamide | Active comparator | Drug: Tenofovir alafenamide25mg one tablet orally once a day for 4 weeks, Day 14 to Day 42 |
| Tenofovir Disoproxil Fumarate | Active comparator | Drug: Tenofovir Disoproxil Fumarate300mg one tablet orally once daily for 4 weeks, Day 14 to Day 42 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Aged 18 to 55 years.
- Able to provide informed consent.
- Willing to allow samples and data to be stored and shared for future research.
- Agrees to use a barrier method of contraception or abstain from sexual activity starting at screening though the end of study participation.
Key exclusion criteria (48 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Current infection with HIV or hepatitis A, B, or C.
- Body mass index (BMI) <18.5 kg/m^2 or >30.0 kg/m^2.
- Weight change >5% in the past 6 months.
- History of or current cardiovascular disease such as congestive heart failure, heart block, or clinically relevant abnormal ECG as determined by investigators.
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 |
|---|---|---|
| Dolutegravir (DTG) AND Tenofovir alafenamide (TAF)50mg dolutegravir (DTG) one tablet AND 25mg tenofovir alafenamide (TAF) one tablet together, orally once daily for 4 wks (Day 14 to Day 42) | Drug | Dolutegravir AND Tenofovir alafenamide |
| Tenofovir Disoproxil Fumarate300mg tenofovir disoproxil fumarate (TDF) one tablet orally once daily for 4 wks (Day 14 to Day 42) | Drug | Tenofovir Disoproxil Fumarate |
| Dolutegravir50mg dolutegravir (DTG) one tablet orally once daily for 4 wks (Day 14 to Day 42) | Drug | Dolutegravir |
| Tenofovir alafenamide25mg tenofovir alafenamide (TAF) one tablet orally once a day for 4 wks (Day 14 to Day 42) | Drug | Tenofovir alafenamide |
Primary outcome
Change in plasma metabolites from ARV initiation to the end of the 4 week period of ARV therapy with each treatment
Time frame: Day 14/Wk2 to Day 42/Wk6 of ARV therapy for each of 4 drug regimen.
To determine if TAF or DTG or TDF or DTG/TAF induce changes in plasma metabolites in the 4wks of therapy
4 secondary outcomes
Encompassing transcriptomic changes, metabolic alterations, lipidomic shifts, and proteomic variations.
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
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.
Time frame: Throughout study - Baseline to Day 42/Wk 6
Multi-omic comparisons between DTG and/or TAF versus TDF.
Time frame: Throughout study - Baseline to Day 42/Wk 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Background: PubMed 27562742Squires K, Kityo C, Hodder S, Johnson M, Voronin E, Hagins D, Avihingsanon A, Koenig E, Jiang S, White K, Cheng A, Szwarcberg J, Cao H. Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. Lancet HIV. 2016 Sep;3(9):e410-e420. doi: 10.1016/S2352-3018(16)30016-9. Epub 2016 May 27.
- Background: PubMed 26424673Molina JM, Clotet B, van Lunzen J, Lazzarin A, Cavassini M, Henry K, Kulagin V, Givens N, de Oliveira CF, Brennan C; FLAMINGO study team. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. 2015 Apr;2(4):e127-36. doi: 10.1016/S2352-3018(15)00027-2. Epub 2015 Mar 10.
- Background: PubMed 25285539Lennox JL, Landovitz RJ, Ribaudo HJ, Ofotokun I, Na LH, Godfrey C, Kuritzkes DR, Sagar M, Brown TT, Cohn SE, McComsey GA, Aweeka F, Fichtenbaum CJ, Presti RM, Koletar SL, Haas DW, Patterson KB, Benson CA, Baugh BP, Leavitt RY, Rooney JF, Seekins D, Currier JS; ACTG A5257 Team. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014 Oct 7;161(7):461-71. doi: 10.7326/M14-1084.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. We have no plans to share data with anyone outside of the study team
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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.
Brian P Epling, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dolutegravir (DTG) AND Tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate and Dolutegravir in people with Healthy Volunteer and Weight Gain, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 5 inclusion and 48 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: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mary E McLaughlin, R.N. ((301) 435-8001, mmclaughli@niaid.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma metabolites from ARV initiation to the end of the 4 week period of ARV therapy with each treatment (time frame: Day 14/Wk2 to Day 42/Wk6 of ARV therapy for each of 4 drug regimen.). 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 NCT05652478, which also lists 3 linked publications.
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 29 Sep 2026.