This clinical trial is a Phase II study designed to test the safety and effectiveness of a combination of dasatinib and quercetin (D+Q) in improving physical function for people with HIV who are frail or prefrail. The study will involve 80 participants, all aged 50 or older, who have been living with HIV for at least 10 years determined to meet criteria for diagnosis of frail or prefrail and are currently on a stable antiretroviral therapy with viral suppression.

Participants will be randomly assigned to one of two groups: one group will receive the D+Q treatment, and the other will receive a placebo. The treatment will be given in six cycles over 12 weeks, with participants taking the medication for two days followed by 12 days without treatment. After the 12-week treatment period, participants will be monitored for another 12 weeks to assess the long-term effects.

The study aims to determine if D+Q can improve physical function and other health outcomes in this population. Randomization will be stratified by sex and age to ensure balanced groups.

Inclusion Criteria:

1. Must be an older person with confirmed diagnosis of HIV-1, defined as ≥ 50 years at study entry.
2. Must have been diagnosed with HIV at least 10 years ago, as confirmed by medical records or self-report.
3. Must be on a stable effective combination antiretroviral therapy (ART) regimen, with no changes in the regimen within 12 weeks before joining the study with 2 or more consecutive HIV-RNA levels < 50 copies/mL within 48 weeks prior to study entry.
4. Must meet one or more Fried Frailty Phenotype criteria w/in 60 days prior to entry.
5. Must have eGFR > 30 using CKD-EPI per 2021 calculation equation.

Exclusion Criteria:

1. Have used quercetin or dasatinib before.
2. Need to take medications that affect CYP3A4 or interact with dasatinib (e.g., certain HIV medications).
3. Have an active cancer (except non-melanoma skin cancer).
4. Have active liver disease with a Child Pugh score greater than 6, or other significant liver problems.
5. Are on dialysis or have had a kidney transplant.
6. Have had a heart attack, angina, stroke, or mini-stroke in the last 6 months.
7. Have a known history of pulmonary arterial hypertension or other respiratory disease requiring supplemental oxygen within 60 days before joining the study.
8. Have uncontrolled diabetes with an HgbA1c level greater than 8% within 60 days before joining the study.
9. Have substance use that might interfere with study participation, as determined by the site investigator.
10. Have had a significant illness within 60 days before joining the study.

Individual participant data that underlie results in the publication, after deidentification.

Beginning 3 months following publication and available throughout period of funding of the ACTG (Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections) by NIH.

• With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG (Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections).
• For what types of analyses? To achieve aims in the proposal approved by the ACTG.
• By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.