This study will test if the medicine dasatinib can lower the hidden amount of HIV in the body, called the HIV "reservoir." It will also check if dasatinib is safe and easy to take for people living with HIV who have a suppressed viral load while on antiretroviral therapy (ART). Adults 18 years or older who have been on ART for at least 48 months and have had a suppressed HIV-1 viral load for at least 36 months may be able to join.

People will be randomly assigned to take dasatinib 100 mg by mouth once a day or a look-alike substance with no drug, called a placebo, for 12 weeks. Neither participants nor researchers will know who gets which (double-blind). The study team will do regular health checks and blood tests to track safety, tolerability, the HIV reservoir, and changes in immune cells.

The study lasts 36 weeks total: 12 weeks of treatment and 24 weeks of follow-up, with clinic visits and possible phone calls. Fourteen people will take part; eight will get dasatinib and six will get placebo. Dasatinib may lower the HIV reservoir, but this is not guaranteed. All medicines can cause side effects, called adverse events (AE). The study team will watch closely and provide medical support. Joining is your choice, and you can leave at any time. If you leave, the team will talk with you about next steps for your care.

Inclusion Criteria:

• HIV-1 infection

• Active antiretroviral therapy received continuously for 48 months (or longer)

• CD4+ cell count >450 cells/mm3 obtained within 12 months prior to study entry

• Plasma HIV-1 RNA level below the lower limit of quantification within 90 days prior to study entry

• Plasma HIV-1 RNA levels below the lower limit of quantification for >36 months at time of study entry

• The following laboratory values obtained within 90 days prior to entry:

  • Absolute neutrophil count (ANC) above the lower limit of normal
  • Hemoglobin above the lower limit of normal
  • Platelet count above the lower limit of normal
  • Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase <1.5 x ULN
  • Total bilirubin <1.5 x ULN
  • Negative hepatitis B virus (HBV) surface antigen (HBsAg)
  • Negative HBV core antibody with one exception: individuals with positive HBV core antibody and HBV surface antibody are eligible for enrollment
  • Negative hepatitis C virus (HCV) antibody (anti-HCV) or, if the anti-HCV is positive, a negative HCV RNA PCR
  • Estimated glomerular filtration rate (eGFR) >70 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) 2021 equation or serum creatinine <1.2 x ULN

• QTc interval <450 milliseconds on EKG performed at screening visit

• Women who are able to become pregnant must have a negative serum or urine pregnancy test at screening and within 48 hours prior to study entry

• Individuals (male or female) who are having sex that could lead to pregnancy, must agree to use at least two effective means of contraception when engaging in sexual activities that can result in pregnancy, from the time of enrollment through 60 days following the last dose of dasatinib

• Able to swallow pills without difficulty.

• Ability and willingness of participant or legally authorized representative to provide informed consent

• Ability and willingness of participant to continue same ART regimen throughout the study

Exclusion Criteria:

• Pre-ART viral load known to be <2000 copies/mL (HIV controller)
• Known to have initiated ART during acute HIV infection
• Presence of a drug-resistant virus with no alternative ART regimens available in the event that current ART regimen becomes compromised as a result of this study
• Current pregnancy or breastfeeding or pregnancy planning during study participation
• Recent hospitalization or surgery within 90 days prior to entry
• Recent infection requiring intravenous antibiotics within 90 days prior to entry
• Any evidence of hepatic impairment
• Any known prior (lasting >180 days) or current history of gastrointestinal-related diseases
• Active malignancy including myelodysplastic syndrome or myeloproliferative disease.
• Any known prior (lasting >180 days) or current history of hematologic illness
• Any known prior (lasting >180 days) or current history of cardiac-related diseases
• Untreated hypothyroidism
• Treatment for TB within the past 90 days.
• Current respiratory disease requiring supplemental oxygen
• Exposure to any systemic immunomodulatory drug (including maraviroc) in the 16 weeks prior to study entry
• Exposure to anticoagulant or anti-platelet medications in the 16 weeks prior to study entry
• Active use of medications known to prolong the QT interval
• Known family history of Long QT Syndrome in a first-degree relative (i.e., parent, offspring, or sibling)
• Active use of medications known to moderately or strongly induce or inhibit CYP3A4, including ART regimens that contain protease inhibitors, efavirenz, etravirine, or cobicistat at the time of screening or study entry
• Current substance use which is likely to interfere with the conduct of the study
• Anticipated conflict or inability to attend and complete all protocol-scheduled study visits and assessments
• Known allergy/sensitivity or any hypersensitivity to components of dasatinib or its formulation
• Active use of azithromycin, Ondansetron, Pentamidine at study entry

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.