Intervention: Cenicriviroc
Trial phase: Phase 2
SMILES: CCCCOCCOc1ccc(-c2ccc3c(c2)/C=C(/C(=O)Nc2ccc([S@@+]([O-])Cc4cncn4CCC)cc2)CCCN3CC(C)C)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 20
Group description: cenicriviroc 50 mg tablets, number of tablets adjusted for other antiretroviral medications or other drugs, given once daily

cenicriviroc: cenicriviroc given once daily for 24 weeks; number of pills dependent on recommended modifications based on patient's other antiretroviral medications and certain other medications anticipated to interact with cenicriviroc
Eligibility criteria:
Inclusion Criteria:

4.2.1.1 Documentation of HIV-1 infection by an FDA approved test at any time prior to study entry
On ARV medication uninterrupted for > 1 year leading up to the screening period
Screening plasma HIV RNA < 50 copies/ml within 3 months of entry
Willingness for males and females of childbearing potential to utilize 2 effective contraception methods (2 separate forms, one of which must be an effective barrier method), be non-heterosexually active or have a an exclusive vasectomized partner from screening throughout the duration of the study treatment and for 30 days following the last dose of study drugs.
Age 18 to 70 years
Ability and willingness to provide written informed consent
Mild to moderate cognitive impairment with global neuropsychological (NP) test (NPZglobal) score of < -0.5 or a neurocognitive abnormality (<-0.5) in at least one cognitive domain known to be typically affected by HIV OR unimpaired
On antiretroviral (ARV) therapy consisting of nucleoside reverse transcriptase inhibitors, atazanavir with/or without ritonavir, darunavir plus ritonavir, dolutegravir, raltegravir or efavirenz.

Exclusion Criteria:

Receiving or used a CCR5 antagonist within 6 months of study entry
Plasma HIV RNA > 100 copies/ml within 6 mo. of screening
HIV-2
Chronic hepatitis B (positive hepatitis B surface antigen)
Chronic hepatitis C (positive hepatitis C antibody), except with proof of viral clearance and normal liver function tests
Active or chronic liver disease
Active or inadequately treated tuberculosis infection, or inadequate treatment for a positive purified protein derivative test. Adequate treatment meets current recommendations of the Center for Disease Control, NIH and the HIV Medicine Association of the Infectious Diseases Society of America (IDSA) guidelines or other Center for Disease Control recommendations if patient was treated before the current recommendations or before coinfection with HIV.
Prior/current diagnosis with other intracellular pathogens (Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans).
Uncontrolled seizures
Current or past malignancies excluding basal cell cancer and Kaposi's sarcoma (skin).
Immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of entry.
Requirement for acute therapy for AIDS-defining or other serious medical illnesses within 14 days of entry.
Other chronic illnesses including hematologic, pulmonary, autoimmune diseases and endocrinopathies, except for stable controlled diabetes or cardiovascular disease in the view of the investigator and stable testosterone or thyroid therapy.
Known hypersensitivity to CVC or its excipients
Anticipated need for prescription medication not allowed in the study. Unwilling to stop eating grapefruit or using St. John's wort).
Chronic use of over the counter medications unless approved by Study Investigator
Hemoglobin < 8.5; Absolute neutrophil count < 1000; Platelet count < 100,000; serum glutamate oxaloacetate and pyruvate transaminase > 2.5x upper limit of normal ; Lipase > 2.0 x upper limit of normal
Estimated creatinine clearance < 30 mL/min(Cockcroft and Gault 1979)
Bradycardia, sinus rhythm <50 beats/min (bpm).
Presence of any condition that would interfere with the absorption, distribution, metabolism, or excretion of the drug
Current active illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with protocol requirements
Pregnancy or breast-feeding
History of moderate (Child-Pugh class B) or severe (Child-Pugh C) hepatic impairment
Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable
For MRI substudy [impaired]: Any factor that precludes MRI scan including presence of metal or exposure to metal work (e.g. metal grinder/worker) and claustrophobia
For MRI substudy [impaired]: Any central nervous system pathology which, in the judgment of the investigator, will interfere with the ability to assess study change in magnetic resonance spectroscopy
4.2.2.28 For lumbar puncture substudy: Thrombocytopenia or other bleeding disorders (including ongoing anticoagulant therapy), suspected increased intracranial pressure or spinal epidural abscess, or any other factor which would increase risk of complications following lumbar puncture