Dasatinib for HIV-1 Reservoir Reduction

Ki vehet részt

• 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 ≤425 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. Permissible ART regimens consist of one or two nucleoside analogs and an integrase inhibitor

Ki nem vehet részt

• 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
• Recent hospitalization or surgery within 90 days prior to entry
• Recent infection requiring intravenous antibiotics within 90 days prior to entry
• Any known prior (lasting >180 days) or current history of gastrointestinal-related diseases
• 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
• Exposure to any systemic immunomodulatory drug (including maraviroc) in the 16 weeks prior to study entry
• 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
• Pre-ART viral load known to be <2000 copies/mL (HIV controller)
• Known to have initiated ART during acute HIV infection
• Any evidence of hepatic impairment
• Active malignancy including myelodysplastic syndrome or myeloproliferative disease
• Current respiratory disease requiring supplemental oxygen
• Known allergy/sensitivity or any hypersensitivity to components of dasatinib or its formulation
• 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)
• Current pregnancy or breastfeeding or pregnancy planning during study participation
• Untreated hypothyroidism
• Treatment for TB within the past 90 days
• 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
• Active use of azithromycin, Ondansetron, Pentamidine at study entry