Evaluating the Safety and Tolerability of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults

Inclusion Criteria:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or historical plasma HIV-1 RNA viral load. More information on this criterion is available in the protocol.
• CD4+ T cell count greater than 350 cells/mm^3 within 45 days prior to study entry at any U.S. laboratory that has a CLIA (Clinical Laboratory Improvement Amendments) certification or its equivalent

• Documentation of virologic suppression defined as:

  • Have virologic suppression defined as HIV-1 RNA level below the limit of quantification (eg, less than 40, less than 50, or less than 75 copies/mL, depending on the assay) using an FDA-approved assay with a quantification limit of 75 copies/mL or lower for at least 48 weeks prior to study entry performed by any laboratory that has a CLIA certification or its equivalent. Single determinations that are between the assay quantification limit and 500 copies/mL (ie, "blips") are allowed as long as the preceding and subsequent determinations are below the level of quantification. The screening value may serve as the subsequent undetectable value following a blip.
• Screening HIV-1 RNA level below the limit of quantification (eg, less than 20, less than 40, less than 50, or less than 75 copies/mL, depending on the assay) using a FDA-approved assay with a quantification limit of 75 copies/mL or lower performed by any laboratory that has a CLIA certification or its equivalent within 45 days prior to study entry.
• Tuberculosis (TB) screening within 365 days of the screening visit diagnosed by tuberculin skin test or interferon gamma release assay
• Currently on continuous ART for at least 730 days prior to study entry, defined as continuous ART for the 730 days period, inclusive, prior to study entry with no ART interruption longer than 7 consecutive days. NOTE: The current regimen must include TDF/FTC, TAF/FTC, TDF+3TC, or ABC/3TC; plus a nonnucleoside reverse transcriptase inhibitor or integrase strand transfer inhibitor (NNRTI or INSTI, not containing cobicistat) for at least 60 days, inclusive, prior to study entry.

• The following laboratory values obtained within 45 days prior to entry by any U.S. laboratory that has a CLIA certification or its equivalent:

  • Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3
  • Hemoglobin greater than or equal to 12.0 g/dL
  • Platelets greater than or equal to 200,000/mm^3
  • Calculated creatinine clearance (CrCl) greater than 80 mL/min, or greater than or equal to 70 mL/min for participants on a DTG-containing regimen (by Cockcroft Gault equation). NOTE: A calculator for estimating the CrCl can be found at www.fstrf.org/ACTG/ccc.html
  • Aspartate aminotransferase (AST) (SGOT) less than or equal to 1.5x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) (SGPT) less than or equal to 1.5x ULN
  • Alkaline phosphatase less than or equal to 1.5x ULN
• For females of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must have a negative serum or urine pregnancy test with a sensitivity of 25 mIU/mL within 72 hours, inclusive, prior to study entry
• All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization)

• All participants of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception while receiving the study drugs and for 7 weeks after stopping the medications. Acceptable forms of contraceptive include:

  • Condoms (male or female) with or without a spermicidal agent
  • Diaphragm or cervical cap with spermicide
  • Intrauterine device (IUD)
  • Hormone-based contraceptive (must contain at least 35 mcg of ethinyl estradiol)
• Women who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy) or men who have documented azoospermia or undergone vasectomy are eligible to start study drugs without requiring the use of contraceptives. Acceptable documentation of sterilization and menopause is specified in the protocol.
• Men and women age greater than or equal to 18 and less than 75 years
• Ability and willingness of participant or legal representative to provide written informed consent and attend study visits as scheduled at a participating site

Exclusion Criteria:

• A current or past history of progressive multifocal leukoencephalopathy
• Breastfeeding or pregnancy
• Use of strong inhibitors or inducers of CYP3A4 including a protease inhibitor, cobicistat or entry inhibitors as part of the current ART regimen or other concomitant therapy
• Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
• Acute or serious illness or infection requiring systemic treatment and/or hospitalization within 60 days prior to entry
• Vaccinations (other than influenza) less than or equal to 45 days prior to the study entry visit. NOTE: Influenza vaccine is permitted. Participants are encouraged to get this vaccine greater than or equal to 7 days prior to the study pre-entry visit.
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy or investigational therapy less than or equal to 60 days prior to study entry

• Any current diagnosis or past history of a significant pulmonary, neurologic, cardiac, renal, or hepatic disorder prior to study entry, excluding treated HIV or treated hypertension. Diagnoses that would lead to exclusion include, but are not limited to the following:

  • CDC category C AIDS-indicator conditions
  • NOTE A: Except HIV encephalopathy, HIV wasting, esophageal candidiasis, or pneumocystis pneumonia without dissemination.
  • NOTE B: List available: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm
  • Herpes zoster (dermatomal or non-dermatomal). NOTE: A history of prior chickenpox is not exclusionary.
  • Lymphoproliferative malignancy
  • Chronic or severe psychiatric condition
  • Chronic liver disease of any etiology and any degree of severity
  • Chronic hepatitis
  • Disseminated fungal infection of any type or duration that is not limited to cutaneous or mucocutaneous surfaces
  • A medical disorder that predisposes to bleeding
  • NOTE: If a site investigator is unsure of whether a history of a significant medical or psychiatric condition should lead to participant exclusion, the investigator should err on the side of safety if s/he believes that an active or clinically resolved disorder may put the participant at risk from participation in the study, influence the results of the study, or affect the participant's ability to participate. If still uncertain, then the site should contact the protocol team (actg.corea5336@fstrf.org) to assist in a determination.
• Change in the ART regimen within 12 weeks, inclusive, prior to study entry or intended modification of ART during the study. NOTE: Modifications of ART doses during the 12 weeks prior to study entry are permitted. In addition, the change in formulation (e.g., from standard formulation to fixed-dose combination) is allowed within 12 weeks prior to study entry. A within class single drug substitution (e.g., switch from nevirapine to efavirenz or from atazanavir to darunavir) is allowed within 12 weeks prior to study entry, with the exception of a switch between any other NRTI to/from abacavir. No other changes in ART within the 12 weeks prior to study entry are permitted. However, participants need to be receiving (and tolerating) an allowable (for study purposes) ART regimen for at least 4 weeks prior to study entry.
• History of untreated latent tuberculosis infection (LTBI) diagnosed by tuberculin skin test or interferon gamma release assay. LTBI treatment would consist of 9 months of isoniazid or an equivalent therapy completed at least 4 weeks prior to study entry.