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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
Fold Change in the Level of Interleukin 1 Alpha (IL-1 Alpha)
Laboratory testing was not performed so the data are not available.
Fold Change in the Level of Interferon Gamma-induced Protein 10 (IP-10)
Laboratory testing was not performed so the data are not available.
Fold Change in the Level of Macrophage Colony-stimulating Factor
Laboratory testing was not performed so the data are not available.
Fold Change in the Level of Neopterin
Data not available because the testing lab reported that the values were unreliable.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Change in CD69
Data not available because the team decided they were no longer clinically relevant, so samples were not tested for CD69.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.