Phase 2
Completed N=32
Safety and Efficacy of Sirolimus for HIV Reservoir Reduction in Individuals on Suppressive Antiretroviral Therapy (ART)
Source: ClinicalTrials.gov NCT02440789 ↗Enrolled (actual)
32
Serious AEs
3.3%
Results posted
Dec 2019
Primary outcomePrimary: Number of Participants Who Met the Study-defined Composite Safety Endpoint — 3 Participants
Summary
The purpose of this study was to find out about the safety of sirolimus in individuals with HIV infection who were also being treated with ART. The investigators wanted to learn whether sirolimus decreases inflammation and immune activation in the body; whether sirolimus changes the level of HIV in the participants' blood; and how sirolimus interacts with ART in the blood. Sirolimus is approved by the Food and Drug Administration (FDA) to prevent organ rejection in patients aged 13 years and older receiving kidney transplants. Sirolimus had also been used for the prevention of complications after stem cell transplants and as a treatment for certain kinds of cancers in HIV-infected patients.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Met the Study-defined Composite Safety Endpoint |
3 | — |
| PRIMARY Efficacy - Immunologic: Frequency of HIV-1 Gag-specific CD8+ T-cells by Intracellular Staining for IFN-gamma |
0.11; 0.11 | — |
| PRIMARY Efficacy - Immunologic: Change in HIV-1 Gag-specific CD8+ T-cells by Intracellular Staining for IFN-gamma |
-0.01 | 0.56 |
| PRIMARY Efficacy - Virologic: CD4+ T-cell-associated HIV-1 RNA |
2.56; 2.35 | — |
| PRIMARY Efficacy - Virologic: Change in CD4+ T-cell-associated HIV-1 RNA |
-0.21 | 0.11 |
| PRIMARY Efficacy - Virologic: Plasma HIV-1 RNA by SCA |
8; 8; 9; 7; 8; 8 | — |
| PRIMARY Efficacy - Virologic: Change in Plasma HIV-1 RNA by SCA |
-0.01 | 0.93 |
| SECONDARY Measurement of CD4+ T-cell Counts |
937; 858; 820; 820; 891 | — |
| SECONDARY Change in CD4+ T-cell Counts |
-118 | 0.041 sig |
| SECONDARY Measurement of HIV-1 RNA Levels |
16; 0; 16; 0; 16; 0 | — |
| SECONDARY Cell-associated HIV-1 DNA Levels in Total CD4+ Cells |
2.65; 2.45; 2.48; 2.49; 2.51 | — |
| SECONDARY Change in Cell-associated HIV-1 DNA Levels in Total CD4+ Cells |
-0.16 | 0.008 sig |
| SECONDARY Measurement of HIV-1 Gag-specific CD107a+ CD8+ T-cell Responses |
0.01; 0.02; 0.01; 0.05; 0.02 | — |
| SECONDARY Change in HIV-1 Gag-specific CD107a+ CD8+ T-cell Responses |
0.04 | 0.26 |
| SECONDARY Measurement of HIV-1 Gag-specific CD40L+ CD8+ T-cell Responses |
0.02; 1.15; 0.01; 0.03; 0.01 | — |
| SECONDARY Change in HIV-1 Gag-specific CD40L+ CD8+ T-cell Responses |
0.01 | 0.75 |
| SECONDARY Measurement of HIV-1 Gag-specific IL-2+ CD8+ T-cell Responses |
0.02; 0.01; 0.02; 0.02; 0.03 | — |
| SECONDARY Change in HIV-1 Gag-specific IL-2+ CD8+ T-cell Responses |
— | 0.97 |
| SECONDARY Measurement of HIV-1 Gag-specific MIP1B+ CD8+ T-cell Responses |
0.09; 0.51; 0.08; 0.09; 0.08 | — |
| SECONDARY Change in HIV-1 Gag-specific MIP1B+ CD8+ T-cell Responses |
-0.01 | 0.7 |
| SECONDARY Measurement of HIV-1 Gag-specific TNF-alpha+ CD8+ T-cell Responses |
0.04; 0.04; 0.03; 0.05; 0.04 | — |
| SECONDARY Change in HIV-1 Gag-specific TNF-alpha+ CD8+ T-cell Responses |
0.01 | 0.47 |
| SECONDARY Measurement of HIV-1 Gag-specific CD4+ T-cell by Intracellular Staining for IFN-gamma Responses |
0.06; 0.04; 0.05; 0.06; 0.04 | — |
| SECONDARY Change in HIV-1 Gag-specific CD4+ T-cell by Intracellular Staining for IFN-gamma Responses |
— | 0.72 |
| SECONDARY Measurement of HIV-1 Gag-specific CD107a+ CD4+ T-cell Responses |
0.01; 0.01; 0.01; 0.03; 0.02 | — |
| SECONDARY Change in HIV-1 Gag-specific CD107a+ CD4+ T-cell Responses |
0.02 | 0.28 |
| SECONDARY Measurement of HIV-1 Gag-specific CD40L+ CD4+ T-cell Responses |
0.08; 0.06; 0.1; 0.08; 0.08 | — |
| SECONDARY Change in HIV-1 Gag-specific CD40L+ CD4+ T-cell Responses |
-0.01 | 0.7 |
| SECONDARY Measurement of HIV-1 Gag-specific IL-2+ CD4+ T-cell Responses |
0.03; 0.04; 0.04; 0.08; 0.04 | — |
| SECONDARY Change in HIV-1 Gag-specific IL-2+ CD4+ T-cell Responses |
0.04 | 0.28 |
| SECONDARY Measurement of HIV-1 Gag-specific MIP1B+ CD4+ T-cell Responses |
0.01; 0.01; 0.01; 0.01; 0.01 | — |
| SECONDARY Change in HIV-1 Gag-specific MIP1B+ CD4+ T-cell Responses |
— | 0.77 |
| SECONDARY Measurement of HIV-1 Gag-specific TNF-alpha+ CD4+ T-cell Responses |
0.04; 0.04; 0.03; 0.04; 0.04 | — |
| SECONDARY Change in HIV-1 Gag-specific TNF-alpha+ CD4+ T-cell Responses |
— | 0.93 |
| SECONDARY Measurement of %CD69+ CD4+ T-cells |
6.3; 6.1; 5.8; 6.1; 5.9 | — |
| SECONDARY Change in of %CD69+ CD4+ T-cells |
-0.17 | 0.65 |
| SECONDARY Measurement of %CD69+ CD8+ T-cells |
8.6; 8.4; 7.9; 8.1; 8.2 | — |
| SECONDARY Change in of %CD69+ CD8+ T-cells |
-0.52 | 0.22 |
| SECONDARY Measurement of %Ki67+ CD4+ T-cells |
2.4; 2.2; 2.2; 1.9; 2.4 | — |
| SECONDARY Change in of %Ki67+ CD4+ T-cells |
-0.51 | 0.031 sig |
| SECONDARY Measurement of %Ki67+ CD8+ T-cells |
1.8; 1; 1.4; 1.2; 1.7 | — |
| SECONDARY Change in of %Ki67+ CD8+ T-cells |
-0.54 | 0.005 sig |
| SECONDARY Measurement of %PD1+ CD4+ T-cells |
38.4; 39; 38.8; 38.8; 35.5 | — |
| SECONDARY Change in of %PD1+ CD4+ T-cells |
0.42 | 0.69 |
| SECONDARY Measurement of %PD1+ CD8+ T-cells |
29.4; 28.4; 28.4; 26.6; 25.5 | — |
| SECONDARY Change in of %PD1+ CD8+ T-cells |
-2.85 | 0.008 sig |
Eligibility Criteria
Inclusion Criteria
- HIV-1 infection
- On continuous ART for ≥24 months prior to study entry.
- CD4+ cell count ≥350 cells/mm^3
- Plasma HIV-1 RNA below the level of quantification for ≥24 months.
- White blood cell (WBC) ≥3000/mm^3
- Platelet count ≥125,000/mm^3
- Absolute neutrophil count (ANC) >1300/mm^3
- Aspartate aminotransferase (AST) <1.25 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) <1.25 x ULN
- Calculated creatinine clearance (CrCl) ≥60 mL/min
- Fasting or non-fasting triglyceride level ≤350 mg/dL
- Fasting or non-fasting LDL <160 mg/dL
- Urine protein to urine creatinine ratio ≤1 g/g from random urine collection
Exclusion Criteria
- Serious illness requiring systemic treatment and/or hospitalization
- Documentation of any CDC Category C AIDS-indicator condition or oropharyngeal candidiasis (thrush)
- Intended modification of ART during the study.
- Latent tuberculosis (TB) infection
- TB disease within 48 weeks prior to study entry requiring treatment.
- History of active hepatitis B (HBV) infection.
- Hepatitis C virus (HCV) RNA-positive
- Previous myelodysplasia syndrome, lymphoproliferative disease, lung disease, malignancies, congestive heart failure, life-threatening fungal infection or herpes-zoster/varicella-zoster viral infection requiring treatment.
- Detectable Epstein-Barr virus (EBV) in blood
- Active infection other than HIV that required receipt of systemic antibiotic therapy by intravenous infusion
- History of major hypersensitivity reaction to macrolide drugs including angioedema, anaphylaxis, drug-induced dermatitis, or hypersensitivity vasculitis.
- Currently pregnant or breastfeeding, or planning to become pregnant prior to or during the study.
- Use of immunomodulators (eg, interleukins, interferons, and cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy.
- Active drug or alcohol use or dependence
- Vaccination within 14 days prior to study entry.
- On or planned to change to a PI-based ART or cobicistat-boosted regimen
- Anti-human papillomavirus (HPV) therapies
Data sourced from ClinicalTrials.gov (NCT02440789). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.