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

A Randomized, Pilot Study of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults

The purpose of this study was to evaluate the safety and tolerability of ruxolitinib in HIV-positive adults who were virologically suppressed and who were on antiretroviral therapy (ART).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Ruxolitinib

Detailed Description

Ruxolitinib is a medication approved by the U.S. Food and Drug Administration (FDA) to treat myelofibrosis, a disorder in which bone marrow is replaced by scar (fibrosis) tissue. Many of the cytokines affected by myelofibrosis are also affected by HIV. Because of this, ruxolitinib may also be a possible treatment for HIV. The purpose of this study was to evaluate the safety and tolerability of ruxolitinib in HIV-positive adults who were on ART and who were virologically suppressed. Researchers evaluated the effect ruxolitinib had on inflammation and immune activation.

This study enrolled HIV-positive adults who were on select ART regimens and who had viral suppression. ART was not provided by the study; participants continued to receive ART from their own health care providers. Participants were randomly assigned to receive either ruxolitinib (Arm A) or no study treatment (Arm B) in 2:1 ratio. Participants in Arm A received ruxolitinib twice a day for 5 weeks. All participants attended study visits at entry (Day 0) and Weeks 1, 2, 4, 5, 10, and 12. These visits included physical examinations, clinical assessments, blood collection, adherence assessments, oral swab collection, and pregnancy testing for female participants. At Weeks 1 and 4, participants in Arm A took part in pharmacokinetic (PK) sampling, which involved having blood drawn several times over 6 to 8 hours.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Alabama CRS
  • California
    • Los Angeles, California, United States, 90035
      • UCLA CARE Center CRS
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center CRS
    • San Francisco, California, United States, 94110
      • Ucsf Hiv/Aids Crs
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1010
      • Washington University Therapeutics (WT) CRS
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Uptown CRS
    • New York, New York, United States, 10010
      • Weill Cornell Chelsea CRS
    • Rochester, New York, United States, 14642
      • University of Rochester Adult HIV Therapeutic Strategies Network CRS
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Cincinnati Clinical Research Site
    • Cleveland, Ohio, United States, 44106
      • Case Clinical Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Therapeutics, CRS
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital Clinical Research Site (TMH CRS) CRS
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Therapeutics (VT) CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-1 infection
• CD4+ T cell count greater than 350 cells/mm^3 within 45 days prior to study entry
• Documented 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
• Screening HIV-1 RNA level below the limit of quantification
• 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:

  • Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3
  • Hemoglobin greater than 12.0 g/dL for men and greater than 11.0 g/dL for women
  • Platelets greater than or equal to 140,000/mm^3
  • Calculated creatinine clearance (CrCl) greater than or equal to 70 mL/min (by Cockcroft Gault equation)
  • 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, 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 were 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
• 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.
• 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 cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, neuropsychiatric, psychiatric, or other serious illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data or affect the participant's ability to participate in the study. Diagnoses that would lead to exclusion include, but were 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 C: A history of prior chickenpox was not exclusionary.
  • Lymphoproliferative malignancy
  • Chronic liver disease of any etiology and any degree of severity
  • Chronic hepatitis, except for hepatitis C that has been cured (defined as a Sustained Virologic Response, which is an undetectable HCV-RNA at 12 weeks or more after completing treatment measured by a sensitive, qualitative, or quantitative HCV-RNA assay)
  • Disseminated fungal infection of any type or duration that is not limited to cutaneous or mucocutaneous surfaces
  • A medical disorder that predisposes to bleeding
• Change in the ART regimen within 12 weeks, inclusive, prior to study entry or intended modification of ART during the study.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Ruxolitinib; Participants received ruxolitinib twice a day for 5 weeks. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.	Drug: Ruxolitinib; 10 mg orally twice daily for 5 weeks
No Intervention: Arm B: No Study Treatment; Participants did not receive any study treatment. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants on the Ruxolitinib Arm Who Experienced Any Safety Milestone Events While On-Treatment	Events defined as safety milestones are listed below and together makeup the composite endpoint.; Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3); Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3); Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART; New or recurrent CDC category C AIDS-indicator condition; HIV-1 associated infection including Herpes zoster; Lymphoproliferative malignancies; Grade 4 or recurrence of Grade 3 anemia/neutropenia; New diagnosis of pneumonia, sepsis, or bacteremia; Discontinuation of Ruxolitinib due to thrombocytopenia; Any Grade 4 or recurrence of Grade 3 toxicity related to study drug Percent experiencing a safety milestone will be reported.	Entry to Week 5
Percentage of Participants Who Experienced Any Safety Milestones On-study From Entry to Week 5	Events defined as safety milestones are listed below and together makeup the composite endpoint.; Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3); Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3); Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART; New or recurrent CDC category C AIDS-indicator condition; HIV-1 associated infection including Herpes zoster; Lymphoproliferative malignancies; Grade 4 or recurrence of Grade 3 anemia/neutropenia; New diagnosis of pneumonia, sepsis, or bacteremia; Occurrence of Grade 2 or higher thrombocytopenia; Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing a safety milestone will be reported.	Entry to Week 5
Percentage of Participants Who Experienced Each Safety Milestone That Occurred On-study From Entry to Week 5	Events defined as safety milestones are listed below.; Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3); Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3); Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART; New or recurrent CDC category C AIDS-indicator condition; HIV-1 associated infection including Herpes zoster; Lymphoproliferative malignancies; Grade 4 or recurrence of Grade 3 anemia/neutropenia; New diagnosis of pneumonia, sepsis, or bacteremia; Occurrence of Grade 2 or higher thrombocytopenia; Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing each safety milestone will be reported. Safety milestone categories are not mutually exclusive.	Entry to Week 5
Number of Participants With Premature Discontinuation of Study Treatment in the Ruxolitinib Arm	Number of participants with premature discontinuation of study treatment are summarized.	Entry to Week 5
Fold Change in the Level of Plasma Interleukin 6 (IL-6) From Baseline to Week 4/5	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Fold change was calculated as the value at Week 4/5 divided by the value at Baseline.	Pre-entry, Entry, Weeks 4 and 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants on the Ruxolitinib Arm Who Experienced Any Safety Milestone Events During Total Follow-up	Events defined as safety milestones are listed below and together makeup the composite endpoint.; Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3); Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3); Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART; New or recurrent CDC category C AIDS-indicator condition; HIV-1 associated infection including Herpes zoster; Lymphoproliferative malignancies; Grade 4 or recurrence of Grade 3 anemia/neutropenia; New diagnosis of pneumonia, sepsis, or bacteremia; Discontinuation of Ruxolitinib due to thrombocytopenia; Any Grade 4 or recurrence of Grade 3 toxicity related to study drug Percent experiencing a safety milestone will be reported.	Entry to Week 12
Percentage of Participants Who Experienced Any Safety Milestones On-study From Entry to Week 12	Events defined as safety milestones are listed below and together makeup the composite endpoint.; Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3); Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3); Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART; New or recurrent CDC category C AIDS-indicator condition; HIV-1 associated infection including Herpes zoster; Lymphoproliferative malignancies; Grade 4 or recurrence of Grade 3 anemia/neutropenia; New diagnosis of pneumonia, sepsis, or bacteremia; Occurrence of Grade 2 or higher thrombocytopenia; Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing a safety milestone will be reported.	Entry to Week 12
Percentage of Participants Who Experienced Each Safety Milestone That Occurred On-study From Entry to Week 12	Events defined as safety milestones are listed below.; Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm3 (for participants with entry CD4+ T cell count < 700 cells/mm3); Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm3); Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART; New or recurrent CDC category C AIDS-indicator condition; HIV-1 associated infection including Herpes zoster; Lymphoproliferative malignancies; Grade 4 or recurrence of Grade 3 anemia/neutropenia; New diagnosis of pneumonia, sepsis, or bacteremia; Occurrence of Grade 2 or higher thrombocytopenia; Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing each safety milestone will be reported. Safety milestone categories are not mutually exclusive.	Entry to Week 12
Number of Participants Who Experienced a Protocol-defined Reportable Adverse Event at Any Post-entry Time Point.	Protocol-defined reportable adverse events include: all diagnoses regardless of grade, Grade 3 or higher sign/symptoms or laboratory values, any signs/symptoms or laboratory values that led to a change in treatment or met ICH, EAE, or SAE guidelines. See the Protocol Section References for links to the EAE manual. This is a subset of the events reported in the Adverse Events section.	Entry to Week 12
Creatinine Clearance	Creatinine clearance was calculated using the Cockcroft Gault equation. The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Change in Creatinine Clearance Values From Entry	Creatinine clearance was calculated using the Cockcroft Gault equation. The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Creatinine	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Change in Creatinine Values From Entry	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Absolute Neutrophil Count (ANC)	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Change in Absolute Neutrophil Count (ANC) Values From Entry	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Hemoglobin	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Change in Hemoglobin Values From Entry	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Platelet Count	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Change in Platelet Counts From Entry	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Aspartate Aminotransferase (AST) (SGOT)	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Change in Aspartate Aminotransferase (AST) (SGOT) Values From Entry	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Alanine Aminotransferase (ALT) (SGPT)	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Change in Alanine Aminotransferase (ALT) (SGPT) Values From Entry	The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.	Entry, Weeks 1, 2, 4, 5, 10, and 12
Fold Change in the Level of Plasma Interleukin 6 (IL-6)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Week 10/12 is defined as the geometric mean of the Week 10 and Week 12 values. Fold change was calculated as the value at Week 10/12 divided by the value at Baseline and the value at Week 4/5 divided by the value at Week 10/12.	Pre-entry, Entry, Weeks 4, 5, 10 and 12
Fold Change in the Level of Soluble CD14 (sCD14)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Fold change was calculated as the value at Week 4/5 divided by the value at Baseline, the value at Week 12 divided by the value at Baseline, and the value at Week 12 divided by the value at Week 4/5.	Pre-entry, Entry, Weeks 4, 5, and 12
Change in CD4+ T Cell Count	Baseline is defined as the average of pre-entry and entry. Absolute change was calculated as the value at Week 2 minus the value at Baseline, the value at week 5 minus the value at baseline, the value at week 12 minus the value at baseline, and the value at week 5 minus the value at week 12.	Pre-entry, Entry, Weeks 2, 5, and 12
Number of Participants With Plasma HIV-1 RNA Level Above the Limit of Quantification	Participants were required to be virally suppressed, with a plasma HIV-1 RNA level below 40 copies/mL. The number of participants with plasma HIV-1 RNA level above the limit of quantification is reported at each time point.	Entry, Weeks 2, 5, and 12
Relative Risks of HIV-1 RNA by Single Copy Assay (SCA) < 0.4 Copies/mL	HIV-1 RNA was measured via Single Copy Assay Using Primer in Integrase (iSCA), results were reported as below or above the assay limit of detection (LOD) (LOD = 0.4 copies/mL). GEE models for binary data were used to calculate the relative risk of having HIV-1 RNA by iSCA <0.4 copies/mL (Week 5 compared to Entry, Week 12 compared to Entry, and Week 12 compared to Week 5).	Entry, Weeks 5 and 12
Fold Change in the Level of Plasma Tumor Necrosis Factor Alpha (TNF Alpha)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in the Level of Plasma Interleukin 1 Beta (IL-1 Beta)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in the Level of Plasma Interleukin 7 (IL-7)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in the Level of Interleukin 1 Alpha (IL-1 Alpha)	Laboratory testing was not performed so the data are not available.	Pre-entry, Entry, Weeks 4, 5, and 12
Fold Change in the Level of Interferon Gamma-induced Protein 10 (IP-10)	Laboratory testing was not performed so the data are not available.	Pre-entry, Entry, Weeks 4, 5, and 12
Fold Change in the Level of Macrophage Colony-stimulating Factor	Laboratory testing was not performed so the data are not available.	Pre-entry, Entry, Weeks 4, 5, and 12
Fold Change in the Level of Neopterin	Data not available because the testing lab reported that the values were unreliable.	Pre-entry, Entry, Weeks 4, 5, and 12
Fold Change in the Level of Plasma Interleukin 10 (IL-10)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in the Level of Plasma Interleukin 15 (IL-15)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in the Level of Plasma Interleukin 18 (IL-18)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in the Level of Plasma Transforming Growth Factor Beta 1 (TGF Beta-1)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in the Level of Plasma Transforming Growth Factor Beta 2 (TGF Beta-2)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in the Level of Plasma Transforming Growth Factor Beta 3 (TGF Beta-3)	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Change in (CD3+CD4+) CD38+HLADR+	Absolute change in the percent of parent cells (CD4+) that express CD38+HLADR+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD8+) CD38+HLADR+	Absolute change in the percent of parent cells (CD8+) that express CD38+HLADR+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD4+) CD25hi+	Absolute change in the percent of parent cells (CD4+) that express CD25hi+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD8+) CD25+	Absolute change in the percent of parent cells (CD8+) that express CD25+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD4+) CD127+	Absolute change in the percent of parent cells (CD4+) that express CD127+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD8+) CD127+	Absolute change in the percent of parent cells (CD8+) that express CD127+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD4+) Ki67+	Absolute change in the percent of parent cells (CD4+) that express Ki67+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD8+) Ki67+	Absolute change in the percent of parent cells (CD8+) that express Ki67+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD4+) Bcl2+	Absolute change in the percent of parent cells (CD4+) that express Bcl2+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD8+) Bcl2+	Absolute change in the percent of parent cells (CD8+) that express Bcl2+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD4+) a4b7+	Absolute change in the percent of parent cells (CD4+) that express a4b7+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD8+) a4b7+	Absolute change in the percent of parent cells (CD8+) that express a4b7+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD4+) CX3CR1+	Absolute change in the percent of parent cells (CD4+) that express CX3CR1+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in (CD3+CD8+) CX3CR1+	Absolute change in the percent of parent cells (CD8+) that express CX3CR1+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in CD69	Data not available because the team decided they were no longer clinically relevant, so samples were not tested for CD69.	Entry, Weeks 5 and 12
Change in PAR-1	Data not available because the team decided they were no longer clinically relevant, so samples were not tested for PAR-1.	Entry, Weeks 5 and 12
Change in Classical Monocytes (CD14+CD16-)	Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Classical Monocytes (CD14+CD16-) Expressing CD163+	Absolute change in the percent of classical monocytes (CD14+CD16-) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Classical Monocytes (CD14+CD16-) Expressing CCR2+	Absolute change in the percent of classical monocytes (CD14+CD16-) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Classical Monocytes (CD14+CD16-) Expressing CX3CR1+	Absolute change in the percent of classical monocytes (CD14+CD16-) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Inflammatory Monocytes (CD14+CD16+)	Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CD163+	Absolute change in the percent of inflammatory monocytes (CD14+CD16-) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CCR2+	Absolute change in the percent of inflammatory monocytes (CD14+CD16+) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CX3CR1+	Absolute change in the percent of inflammatory monocytes (CD14+CD16+) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Patrolling Monocytes (CD14dimCD16+)	Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CD163+	Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CCR2+	Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CX3CR1+	Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.	Entry, Weeks 5 and 12
Fold Change in Cellular HIV-1 DNA	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Fold Change in Cellular HIV-1 Total RNA	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12
Percentage of Participants With Detectable CMV Shedding	Level of CMV shedding was summarized by study week and arm as the percentage of those above and below the assay limit of detection. Detectable CMV shedding was defined as CMV level > 0 copies/ml of elution. The percentage of participants with detectable CMV at any on-treatment time point (ever shedding at weeks 1, 2, 4, or 5) and any post-treatment time point (ever shedding at weeks 10 or 12) was contrasted between study arms.	Pre-entry, Entry, and Weeks 1, 2, 4, 5, 10, and 12
Ruxolitinib Systemic Clearance (CL/F) From 2-compartment Pharmacokinetic (PK)	Ruxolitinib plasma concentrations were fitted to a population 2-compartment distribution model, assuming first-order input, distribution and elimination from the plasma compartment, using nonlinear mixed-effects modeling software. We estimated parameter geometric means and proportional variabilities between subjects (IIV when feasible) and the variability in drug absorption between occasions (IOV week 1 and week 4/5), and related distribution volumes to body weight.	Week 1 and, Week 4/5; blood samples were drawn pre-dose and at 1-1.5, 2.5-4, 4-6, and 6-8 hours post-dosing

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 2 Long-terminal Repeat Sequences [LTRs]	Data not available because all values were below assay limit.	Entry, Week 5, and Week 12
Level of HHV Shedding (EBV, HSV, HHV-6, HHV-7, and HHV-8)	Data not available because no samples were collected to test for these measures as the team decided they were no longer clinically relevant.	Pre-entry, Entry, Weeks 1, 2, 4, 5, 10, and 12
Fold Change in Integrated DNA	All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.	Entry, Weeks 5 and 12

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Vincent Marconi, MD, Emory University; Study Chair: Jeffrey Lennox, MD, Emory University

Publications and helpful links

General Publications

• Marconi VC, Moser C, Gavegnano C, Deeks SG, Lederman MM, Overton ET, Tsibris A, Hunt PW, Kantor A, Sekaly RP, Tressler R, Flexner C, Hurwitz SJ, Moisi D, Clagett B, Hardin WR, Del Rio C, Schinazi RF, Lennox JJ. Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults With Human Immunodeficiency Virus. Clin Infect Dis. 2022 Jan 7;74(1):95-104. doi: 10.1093/cid/ciab212.

Helpful Links

• DAIDS AE Grading Table, Version 2.0, November 2014
• Version 2.0 of the DAIDS EAE Manual

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2016
• Primary Completion (Actual): February 18, 2018
• Study Completion (Actual): April 4, 2018

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 16, 2015
• First Posted (Estimate): June 19, 2015

Study Record Updates

• Last Update Posted (Actual): November 4, 2021
• Last Update Submitted That Met QC Criteria: November 2, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: A5336; 11977 (Registry Identifier: DAIDS-ES)