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.
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.
Current infection with HIV or hepatitis A, B, or C.
Body mass index (BMI) <18.5 kg/m² or >30.0 kg/m².
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.
Parallel
Dolutegravir (DTG) AND Tenofovir alafenamide (TAF)
Drug50mg 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 Fumarate
Drug300mg tenofovir disoproxil fumarate (TDF) one tablet orally once daily for 4 wks (Day 14 to Day 42)
Dolutegravir
Drug50mg dolutegravir (DTG) one tablet orally once daily for 4 wks (Day 14 to Day 42)
Tenofovir alafenamide
Drug25mg 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
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
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.
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.
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.
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