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Protocol Details

A Phase 2 Randomized Cross-Over Design Study of the Early Metabolic Effects of Dolutegravir or Tenofovir Alafenamide in Healthy Volunteers

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Recruitment has not started
Gender: Male & Female
Min Age: 18 Years
Max Age: 55 Years

Referral Letter Required


Population Exclusion(s)



Integrase Strand Transfer Inhibitors

Recruitment Keyword(s)



Healthy Volunteer;
Weight Gain;
Metabolic Effects;
Integrase Strand Transfer Inhibitors

Investigational Drug(s)


Investigational Device(s)



Drug: Tenofovir alafenamide
Drug: Dolutegravir

Supporting Site

National Institute of Allergy and Infectious Diseases


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.


To see how a common INSTI, dolutegravir (DTG), affects how the body uses energy. DTG will be compared with a non-INSTI drug, tenofovir alafenamide (TAF).


Healthy people aged 18 to 55.


Participants will be screened. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function.

Participants will have 2 inpatient stays at the clinic. Each stay will be for 11 nights, with a 3-week break between.

Both DTG and TAF are gel caps swallowed once per day by mouth. Participants will take 1 drug for 8 days during each stay.

Participants will have tests to see how their body uses energy:

They will spend 23 continuous hours in a special room that measures how much oxygen they breathe in and how much carbon dioxide they breathe out. They will do this a total of 6 times.

They will have a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density.

They will lie on a table. Electrodes will be placed on their hands and feet to measure body fat and lean body mass.

They will stand still on a platform for about 30 seconds. High-resolution laser cameras will scan their bodies.

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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 and able to stay in the whole-room indirect calorimetry suite on 6 occasions.

-Willing to reside on the metabolic unit in the Clinical Center for 2 stays of 11 consecutive days over the course of 5 weeks.

-Willing to allow samples and data to be stored and shared for future research.


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 or a trained athlete.

-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.

-History of or current kidney disease or renal insufficiency, or estimated creatinine clearance <=50 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.

-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 or current asthma or chronic obstructive pulmonary disease.

-History of or current glaucoma.

-Psychological conditions by self-report, such as (but not limited to) claustrophobia, clinical depression, bipolar disorders, that would be incompatible with safe and successful participation in this study.

-Pregnancy or within 1 year post-partum.

-Experiences irregular menstrual cycles.


-Blood pressure >140/90 mm Hg or current antihypertensive therapy.

-Anemia, defined as hemoglobin <13 g/dL (males) or <12 g/dL (females).

-History of illicit drug, opioids, 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 medications/dietary supplements/alternative therapies known to alter energy metabolism.

-Current use of prescription medications, including recent use (6 months) of Descovy or Truvada (eg, for purposes of PrEP).

-Any history of exposure to cabotegravir (eg, as participant in research study for this drug).

-Current use of nonprescriptive medications that may have interactions with study drugs 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.

-Participants with dietary allergies, intolerances, or eating patterns that would preclude them from consuming controlled metabolic meals.

-Any condition that, in the opinion of the investigator, contraindicates participation in this study.

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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. PMID: 27562742; PMCID: PMC5825001.

Molina 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. Erratum in: Lancet HIV. 2015 Apr;2(4):e126. PMID: 26424673.

Lennox 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. Erratum in: Ann Intern Med. 2014 Nov 4;161(9):680. PMID: 25285539; PMCID: PMC4412467.

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Principal Investigator

Referral Contact

For more information:

Janaki C. Kuruppu, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
(301) 496-9320

Mary McLaughlin, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 8C404
10 Center Drive
Bethesda, Maryland 20892
(301) 435-8001

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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