Safety and Efficacy of Sirolimus for HIV Reservoir Reduction in Individuals on Suppressive ART
a study on HIV/AIDS
The purpose of this study is to find out about the safety of sirolimus in individuals with HIV infection who are also being treated with ART. The investigators want to learn whether sirolimus will decrease inflammation and immune activation in the body; whether sirolimus will change 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 has 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.
Safety and Efficacy of Sirolimus for HIV Reservoir Reduction in Individuals on Suppressive Antiretroviral Therapy
HIV-1 Infection Sirolimus Everolimus
You can join if…
Open to people ages 18 years and up
- 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, plasma HIV-1 RNA viral load.
NOTE: The term "licensed" refers to a US FDA-approved kit, which is required for all investigational new drug (IND) studies.
WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention)guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
- Currently on continuous ART for ≥24 months prior to study entry. This is defined as continuous active therapy for the 24-month period prior to study entry with no treatment interruption longer than 5 consecutive days and a total duration off treatment of no more than 7 days in the 90 days prior to study entry.
- CD4+ cell count ≥400 cells/mm3 obtained within 60 days prior to study entry at any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices(GCLP) and participates in appropriate external quality assurance programs.
- Plasma HIV-1 RNA below the level of quantification (eg, <20, <40, <50, or <75 copies/mL depending on the assay) for ≥24 months by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs. Participants must have at least one documented HIV-1 RNA below the level of quantification obtained 12-24 months prior to screening and one HIV-1 RNA less than the level of quantification obtained within 12 months prior to the screening HIV-1 RNA.
- One month = 30 days.
- Plasma HIV-1 RNA measurements above the limit of quantification but <200 copies/mL in the 24 months prior to screening are allowed if directly followed by HIV-1 RNA below assay limit, but none in the 6 months prior to screening.
- Plasma HIV-1 RNA level of <40 copies/mL obtained by the Abbott real time assay or<20 copies/mL by the Roche COBAS TaqMan HIV-1 Test, Version 2.0 assay within 60 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
- For females of reproductive potential (defined as women who have not been postmenopausal for at least 24 consecutive months or documentation that the woman has undergone hysterectomy, bilateral oophorectomy, or salpingectomy), negative serum or urine pregnancy test within 48 hours prior to study entry.
NOTE: Patient-reported history is acceptable documentation of hysterectomy and bilateral oophorectomy, tubal ligation, tubal micro-inserts, vasectomy, and menopause.
- Females of reproductive potential who are participating in sexual activity that could lead to pregnancy must agree to initiate effective contraceptives before sirolimus therapy, continue use during sirolimus therapy, and maintain use for at least 12 weeks after sirolimus therapy has been stopped.
Female subjects and/or their male partners MUST agree to use appropriately at least one of the following:
- Condoms (male or female) with or without a spermicidal agent
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD)
- Tubal ligation
- Hormone-based contraceptive
- Sexual activity with an infertile partner is not sexual activity that can lead to pregnancy.
- Females on hormone-based contraceptives at study entry must have been on the same method for at least 90 days prior to study entry.
- Ability and willingness of subject or legal guardian/representative to provide informed consent.
- Laboratory evaluations obtained within 60 days prior to entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCP and participates in appropriate external quality assurance programs.
- White blood cell (WBC) ≥3000/mm3
- Platelet count ≥125,000/mm3
- ANC >1300/mm3
- Aspartate aminotransferase (AST) <1.25 x ULN
- Alanine aminotransferase (ALT) <1.25 x ULN
- Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockcroft-Gault equation:
For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) =CrCl (mL/min)*
- For women, multiply the result by 0.85 = CrCl (mL/min) NOTE: A program to assist in calculations is available on the DMC website at: http://www.fstrf.org/ACTG/ccc.html
- Fasting or non-fasting triglyceride level ≤350 mg/dL
- Fasting or non-fasting LDL <160 mg/dL
- Urine protein to urine creatinine ratio ≤1 gram from random urine collection
You CAN'T join if...
- Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy in the opinion of the site investigator for at least 30 days prior to study entry.
- Documentation of any CDC Category C AIDS-indicator condition or oropharyngeal candidiasis (thrush) within 90 days prior to study entry.(http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm)
- Intended modification of ART during the study.
- Latent tuberculosis (TB) infection defined as a positive PPD ≥5 mm or positive interferon-gamma release assay (IGRA) at any time in the past or evidence of latent TB on the screening chest x-ray without subsequent INH or equivalent antibiotic prophylaxis.
NOTE: Prophylaxis must have been completed at least 48 weeks prior to study entry.
- TB disease within 48 weeks prior to study entry requiring treatment. Subjects with a history of active TB must have completed treatment at least 48 weeks prior to study entry.
- History of or current (within 90 days prior to study entry) active hepatitis B (HBV)infection defined as positive HBV surface antigen test or positive HBV DNA in subjects with isolated HBcAb positivity.
- HCV RNA-positive within 90 days prior to study entry.
NOTE: Subjects who are HCV antibody negative within 90 days prior to study entry are eligible for the study. Those who are not taking HCV therapy and who are HCV antibody-positive but HCV RNA negative within 90 days prior to study entry are eligible for the study.
- Previously diagnosed myelodysplasia syndrome.
- History of lymphoproliferative disease prior to study entry.
- Clinically significant lung disease on the screening chest x-ray that, in the opinion of the site investigator, places the subject at increased risk of lung toxicity (eg,history of pulmonary fibrosis, interstitial lung disease, or pulmonary lymphoproliferative disease).
- Any prior or current diagnosis of solid tumor or hematologic malignancies, including localized skin cancers with or without evidence of metastasis.
- History of congestive heart failure as defined by physician documentation in the medical record at any time prior to screening that required medication for heart failure, or that required medical management within 2 years prior to study entry.
- Detectable Epstein-Barr virus (EBV) in blood by polymerase chain reaction (PCR) within 90 days prior to study entry at any US laboratory that has a CLIA certification or its equivalent.
- Active infection other than HIV that required receipt of systemic antibiotic therapy by intravenous infusion within 90 days prior to study entry.
- Life-threatening fungal infection that in the opinion of the site investigator requires treatment within 48 weeks prior to study entry.
- Herpes-zoster or varicella-zoster viral infection requiring treatment within 90 days prior to study entry or currently on suppressive therapy.
- 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 within 90 days prior to study entry.
- Active drug or alcohol use or dependence that in the opinion of the site investigator would interfere with adherence to study requirements.
- Vaccination (eg, pneumococcal polysaccharide/influenza vaccine) within 14 days prior to study entry.
NOTE: If subjects receive influenza vaccination for routine clinical care during or prior to the screening visit, they may be rescreened 14 days after vaccination.
- On a PI-based ART or cobicistat-boosted regimen within 90 days prior to study entry or plans to change to a PI-based or cobicistat-boosted regimen during the study.
NOTE: Prior PI-based or cobicistat-boosted regimens are allowed.
- Anal or perianal administration of anti-HPV therapies (eg, imiquimod, 5FU, veregen)for 90 days prior to study entry or plans to initiate anti-HPV therapies during the study.
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