Early Metabolic Effects of Dolutegravir or Tenofovir Alefenamide in Healthy Volunteers
Trial Parameters
Brief 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. Researchers want to understand how INSTIs cause weight changes. Objective: 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). Eligibility: Healthy people aged 18 to 55. Design: 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.
Eligibility Criteria
* INCLUSION CRITERIA: 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. EXCLUSION CRITERIA: 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 t