Safety and Impact of Dasatinib on Viral Persistence and Inflammation in People With HIV Under Antiretroviral Treatment

Inclusion Criteria:

• 1. Males and females aged at least 18 years on the day of screening.
• 2. Confirmed HIV-1 infection.
• 3. Receiving suppressive cART for at least 3 years (defined as maintained plasmaviral load <50 copies/mL, allowing for isolated blips [<200 cop/ml, non-consecutive,representing <20% total determinations]).
• 4. Being on the same ART regimen within at least 4 weeks prior to baseline visit.
• 5. Willing and able to be adherent to their ART regimen for the duration of thestudy.
• 6. Willing to comply with the requirements of the protocol and available forfollow-up for the planned duration of the study.
• 7. In the opinion of the Principal Investigator, the candidate has understood theinformation provided and can give written Informed Consent.
• 8. If heterosexually active female of childbearing potential, using an effectivemethod of contraception (hormonal contraception, intra-uterine device (IUD), oranatomical sterility in self or partner) from 14 days prior to the firstInvestigational Medicinal Product (IMP) administration and commit to use it until 3months after the last IMP administration. All female candidates of childbearingpotential who are not heterosexually active at screening, must agree to utilize aneffective method of contraception if they become heterosexually active during thestudy.
• 9. If heterosexually active male, regardless of reproductive potential, sterilizedor agree on the use of an effective method of contraception by his female partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility) fromthe day of the first IMP administration until 3 months after the last IMPadministration. All male candidates who are not heterosexually active at screening,must agree to utilize an effective method of contraception if they becomeheterosexually active during the study.
• 10. If female, willing to undergo urine pregnancy tests at the designated timepoints.
• 11. Willing to accept blood draws at time points specified in the Schedule of Events

Exclusion Criteria:

• 1. If female, pregnant or planning a pregnancy during the entire study or lactating.
• 2. Current treatment with ART regimen that includes ritonavir, cobicistat or withany other drug with known relevant drug-drug interactions with dasatinib.
• 3. Has received any immunotherapy with intent to cure or prevent HIV, includingmonoclonal antibodies, therapeutic or preventive vaccines within 6 months prior tobaseline visit.
• 4. Prior history of exposure to dasatinib or any other Tyrosine Kinase Inhibitor (TKI).
• 5. Prior history of pleural effusion.
• 6. Prior history or clinical manifestations of any physical or psychiatric disorderthat could impair the subject's ability to complete the study.
• 7. Any active AIDS-defining disease or progression of HIV-related disease, exceptcutaneous Kaposi's sarcoma not requiring systemic therapy.
• 8. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma,or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal, orpenile intraepithelial neoplasia.
• 9. Systemic treatment for cancer within 1 year of study entry.
• 10. Known hypersensitivity to any component of the IMP formulation, or severe ormultiple allergies to drugs or pharmaceutical agents.
• 11. Potential participant received or plans to receive:

1. Licensed live attenuated vaccines within 28 days before or after inflammationand immune biomarkers visit (weeks 0, 2, 24 and 48).

2. other vaccines (eg, tetanus, hepatitis A, hepatitis B, rabies, pneumococcal,recombinant Herpes Zoster, Influenza, Coronavirus Disease -19 [COVID-19]vaccines) within 14 days before or after inflammation and immune biomarkersvisits (weeks 0, 2, 24 and 48).

• 12. Receipt of blood products within 3 months of study entry.
• 13. Current or recent use (within last 3 months) of interferon or systemiccorticosteroids or other immunosuppressive agents (use on inhaled steroids forasthma or topic steroids for localized skin conditions are permitted).
• 14. Any other current or prior therapy which, in the opinion of the investigator,would make the individual unsuitable for the study or influence the results of thestudy.
• 15. Any laboratory abnormalities including:

Hematology:

• Hemoglobin <10.0 g/dl,

• Absolute neutrophil count ≤3,000 /mm3,

• Platelets ≤100,000/mm3,

Biochemistry:

• Estimated glomerular filtration rate (eGFR) <60 ml/min,

• Aspartate Transferase (AST) > 2.5 x upper limit of normal (ULN),

• Alanine Transaminase (ALT) > 2.5 x ULN,

Microbiology:

• Positive for hepatitis B surface antigen,

• Positive for hepatitis C antibody, unless confirmed clearance of hepatitis C virus (HCV) infection (spontaneous or following treatment)

• Positive serology indicating active syphilis requiring treatment

• 16. Has a corrected QT interval (QTc interval) ≥470 msec (males) or ≥480 msec (females) upon confirmation on recheck at screening, has a history of riskfactors for Torsades de Pointes (eg, heart failure/cardiomyopathy or familyhistory of long QT syndrome), or is taking concomitant medications that prolongthe QT/QTc interval.