Targeting Platelets in Chronic HIV Infection

HIV infected participants: Inclusion Criteria: * HIV-1 infection * Currently on continuous ART for ≥48 weeks prior to study entry. NOTE: This is defined as continuous active therapy with no treatment interruption longer than 7 consecutive days and a total duration off-treatment of no more than 14 days during the 48 weeks prior to entry. * No change in ART regimen within the 12 weeks prior to study entry (except as noted below). NOTE: Modifications of ART dosing during the 12 weeks prior to entry are permitted. In addition, the change in formulation (eg, from standard formulation to fixed dose combination or single tablet regimen) or dosing (eg, from once a day to twice a day) is allowed within 12 weeks prior to entry. Within-class single drug substitution (eg, switch from nevirapine to efavirenz or from atazanavir to darunavir), are not allowed within 12 weeks prior to entry. No other changes in ART in the 12 weeks prior to entry are permitted. * Screening HIV-1 RNA must be \<50 copies/mL and performed by any FDA-approved assay at any US laboratory that has a CLIA certification or its equivalent within 45 days prior to study entry. * Maintain ART-mediated viral suppression for at least 48 weeks prior to study entry defined as: A. At least one HIV-1 RNA test result obtained at any time point greater than 48 weeks prior to study entry must be BLQ and must be performed by any FDA-approved assay at a CLIA-certified laboratory. AND B. All HIV-1 RNA tests reported during the 48 weeks prior to study entry must be BLQ and must be performed by any FDA-approved assay at a CLIA-certified laboratory. NOTE: A single RNA "blip" of ≤500 copies/mL is permissible if RNA levels most recent before and after (may include the screening HIV-1 RNA test) are BLQ for the assay. * The following laboratory values obtained within 45 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent. * Absolute neutrophil count (ANC) ≥750/mm3 * Hemoglobin ≥9.0 g/dL for female subjects and ≥10.0 g/dL for male subjects * Platelet count \>100,000/mm3 * Prothrombin time (PT) \<1.2 x upper limit normal (ULN) * Partial thromboplastin time (PTT) \<1.5 x ULN * Calculated creatinine clearance (CrCl) ≥30 mL/min, as estimated by the Cockroft-Gault formula * Aspartate aminotransferase (AST) (SGOT) ≤2 x ULN. * Alanine aminotransferase (ALT) (SGPT) ≤2 x ULN. * Alkaline phosphatase ≤2 x ULN. * Total bilirubin ≤2.5 x ULN. If the subject if taking an indinavir- or atazanavir-containing regimen at the time of screening, a total bilirubin of ≤5 x ULN is acceptable. * Female study volunteers of reproductive potential (pre-menopausal women who have not had a sterilization procedure (eg, hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy)) must have a negative serum or urine pregnancy test performed within 24 hours before initiating the protocol-specified medication(s) unless otherwise specified by product labeling. Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH (follicle stimulating hormone) of greater than 40 IU/L or, if FSH testing is not available, they have had amenorrhea for 24 consecutive months. If the female volunteer is not of reproductive potential (women who are menopausal, defined as not having had a menses for at least 12 months with an FSH of greater than 40 IU/L, or if FSH testing is not available, have had amenorrhea for 24 consecutive months, or women who have undergone surgical sterilization, (eg, hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy)), she is eligible without requiring the use of a contraceptive method. Acceptable documentation of sterilization is subject reported history of hysterectomy, bilateral oophorectomy, tubal ligation, tubal micro-insert, menopause, or the partner with vasectomy/azoospermia. * If participating in sexual activity that could lead to pregnancy, the female study volunteer must be willing to use contraception while receiving protocol-specified medication(s) and for the washout period of 4 weeks. At least one of the following methods MUST be used: * Condoms (male or female), with or without a spermicidal agent * Diaphragm or cervical cap with spermicide * Intrauterine device (IUD) * Hormone-based contraceptive As hormone-based contraceptives (oral, transdermal, or subdermal) can affect coagulopathy biomarkers, subjects who plan on using such a contraceptive during the study must be taking the same product for ≥4 weeks prior to screening and be encouraged to continue throughout the duration of the study, if medically feasible. * No documented opportunistic infections within 24 weeks prior to study entry * Karnofsky performance score \>70 within 45 days prior to study entry * Ability and willingness of subject or legal guardian/representative to provide written informed consent. * Willingness to refrain from the use of aspirin or any aspirin-related product (other than the study drug), including NSAIDs, from time of screening visit through the end of the 24 week trial. NOTE: Acetaminophen-based products may be used before and during the trial when analgesics are required. Exclusion Criteria: • Current malignancy (except non-melanoma cancer of the skin not requiring systemic chemotherapy or radiation therapy). NOTE: Carcinoma in situ of the cervix or anus is not considered exclusionary. * Prior history of malignancy if the subject is not disease free for 24 or more weeks prior to study entry. * Current use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin that cannot be interrupted for clinical reasons. Examples of clinical reasons include, but are not limited to, known and documented cardiovascular disease (history of MI, coronary artery bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack, peripheral arterial disease with ABI \<0.9 or claudication). * Current diagnosis of diabetes with HbA1c ≥8% at screening. * Use of lipid-lowering medications including: statins, fibrates, niacin (dose ≥250 mg daily), and fish-oil/omega 3 fatty acids (dose \>1000 mg of marine oils daily). * Known cirrhosis * Known chronic active hepatitis B NOTE: Active hepatitis B is defined as hepatitis B surface antigen positive and hepatitis B DNA positive within 24 weeks prior to study entry; subjects with hepatitis B virus (HBV) DNA BLQ for greater than 24 weeks prior to study entry are eligible. * Known chronic active hepatitis C NOTE: Active hepatitis C is defined as a detectable plasma HCV RNA level within 24 weeks prior to study entry; subjects with HCV RNA BLQ for greater than 24 weeks prior to study entry are eligible. * Known inflammatory conditions, such as, but not limited to, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, inflammatory bowel disease (IBD), chronic pancreatitis, autoimmune hepatitis, Adult Stills disease, Rheumatic heart disease, bursitis. * Breastfeeding or pregnant * Previous intolerance or allergy to aspirin or any aspirin products or clopidogrel. * Frequent use of aspirin or aspirin products (NSAIDs), defined as an average of 2 or more times per week in the last 12 weeks prior to study entry. * Immunosuppressant use, such as, but not limited to, systemic or potentially systemic glucocorticoids (including injected, ie, intra-articular, nasal or inhaled steroids), azathioprine, tacrolimus, mycophenolate, sirolimus, rapamycin, methotrexate, or cyclosporine within 45 days prior to study entry. * Use of any systemic antineoplastic or immunomodulatory treatment, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry. NOTE: Routine standard of care, including hepatitis A and/or B, human papilloma virus, influenza, pneumococcal, and tetanus vaccines are permitted if administered at least 7 days before study entry and before biomarker/peripheral blood mononuclear cell (PBMC) blood collections. * Heavy alcohol use as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) * Alcohol or drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements. * Current use of anticoagulation therapy or conditions requiring use of anticoagulants, use such as, but not limited to warfarin (Coumadin), rivaroxaban (Xarelto), clopidogrel (Plavix), dabigatran (Pradaxa), apixaban (Eliquis), heparin, ticlopidine (Ticlid), Presugrel (Effient). * History of coagulopathy, deep venous thrombosis, pulmonary embolism. * Known active or recent (not fully resolved within 4 weeks prior to study entry) invasive bacterial, fungal, parasitic, or viral infections. NOTE: Recurrent herpes simplex virus (HSV) is not exclusionary. Subjects on antiviral prophylaxis for HSV or VZV are encouraged to remain on treatment for the duration of the study if medically feasible. * Serious illness or trauma requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry. * History of bleeding conditions such as peptic ulcer disease, hemophilia, von Willebrand disease, idiopathic thrombocytopenic purpura. * History of thrombotic disorders such as protein C or S deficiency. * History of gastrointestinal (GI) bleeding within the past 6 months prior to study entry. * History of intracranial hemorrhage. HIV-uninfected participants: Inclusion criteria: • HIV uninfected Exclusion criteria: • Current malignancy (except non-melanoma cancer of the skin not requiring systemic chemotherapy or radiation therapy). NOTE: Carcinoma in situ of the cervix or anus is not considered exclusionary. * Prior history of malignancy if the subject is not disease free for 24 or more weeks prior to study entry. * Current use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin that cannot be interrupted for clinical reasons. * Current diagnosis of diabetes with HbA1c ≥8% at screening. * Use of lipid-lowering medications including: statins, fibrates, niacin (dose ≥250 mg daily), and fish-oil/omega 3 fatty acids (dose \>1000 mg of marine oils daily). * Known cirrhosis * Known chronic active hepatitis B * Known chronic active hepatitis C * Known inflammatory conditions, such as, but not limited to, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, inflammatory bowel disease (IBD), chronic pancreatitis, autoimmune hepatitis, Adult Stills disease, Rheumatic heart disease, bursitis. * Breastfeeding or pregnant * Previous intolerance or allergy to aspirin or any aspirin products or clopidogrel. * Frequent use of aspirin or aspirin products (NSAIDs), defined as an average of 2 or more times per week in the last 12 weeks prior to study entry. * Immunosuppressant use, such as, but not limited to, systemic or potentially systemic glucocorticoids (including injected, ie, intra-articular, nasal or inhaled steroids), azathioprine, tacrolimus, mycophenolate, sirolimus, rapamycin, methotrexate, or cyclosporine within 45 days prior to study entry. * Use of any systemic antineoplastic or immunomodulatory treatment, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry. NOTE: Routine standard of care, including hepatitis A and/or B, human papilloma virus, influenza, pneumococcal, and tetanus vaccines are permitted if administered at least 7 days before study entry and before biomarker/peripheral blood mononuclear cell (PBMC) blood collections. * Heavy alcohol use as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) * Alcohol or drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements. * Current use of anticoagulation therapy or conditions requiring use of anticoagulants, use such as, but not limited to warfarin (Coumadin), rivaroxaban (Xarelto), clopidogrel (Plavix), dabigatran (Pradaxa), apixaban (Eliquis), heparin, ticlopidine (Ticlid), Presugrel (Effient). * History of coagulopathy, deep venous thrombosis, pulmonary embolism. * Known active or recent (not fully resolved within 4 weeks prior to study entry) invasive bacterial, fungal, parasitic, or viral infections. NOTE: Recurrent herpes simplex virus (HSV) is not exclusionary. Subjects on antiviral prophylaxis for HSV or VZV are encouraged to remain on treatment for the duration of the study if medically feasible. * Serious illness or trauma requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry. * History of bleeding conditions such as peptic ulcer disease, hemophilia, von Willebrand disease, idiopathic thrombocytopenic purpura. * History of thrombotic disorders such as protein C or S deficiency. * History of gastrointestinal (GI) bleeding within the past 6 months prior to study entry. * History of intracranial hemorrhage.