Maraviroc on HIV-1 Infected Subjects Who Require Allogeneic Hematopoietic Cell Transplant
- Conditions
- HIV-1-infection
- Registration Number
- NCT03118661
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
The goal of this proposal is to determine the effect of maraviroc when it has been a part of the antiretroviral (ART) regimen given immediately after allogeneic hematopoietic cell transplant (allo-HCT) for HIV-1 infected participants who have a hematopoietic malignancy or other underlying disorder requiring an allogeneic transplant. Maraviroc has been given in practice to alleviate symptoms of graft vs. host disease (GvHD). Given its mechanism of action, it may also have an effect on the reservoir size of HIV-1 in infected patients. This study will inform potential future studies, evaluating the effect of this approach on the incidence and severity of GvHD, and determining its effect on HIV-1 reservoir.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
- Ongoing AIDS-related opportunistic infection (including oral thrush).
- Pregnant and/or breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Time to hematopoietic cell and immune recovery Up to 100 days after transplant -In general, the mean time of engraftment of the donor cells is approximately 90 to 100 days post-transplant and this can be monitored by measuring the percent chimerism of donor cells.
Number of participants who experience chimerism At the time of screening -Chimerism is measured by ≥ 98% of blood cells donor derived
Survival of participants 5 years after transplant -Number of participants who are alive 5 years after transplant
Event free survival 5 years after transplant -Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
HIV-1 proviral DNA levels in peripheral blood Up to week 16 after transplant * Obtained from peripheral blood
* Used to determine if participant can proceed to Step 2Presence and severity of GvHD Through 5 years after transplant -GvHD will be measured using the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: IV. Response Criteria Working Group Report
HIV-1 reactivation in stimulated assay Up to week 16 after transplant * Obtained from peripheral blood
* Used to determine if participant can proceed to Step 2
- Secondary Outcome Measures
Name Time Method Number of participants who achieve a state of functional cure Through 5 years after transplant -Functional Cure: Following the discontinuation of all HIV-1 related treatment interventions, including HAART, a participant will be considered to have achieved an HIV-1 functional cure if for at least 5 years they: maintain an undetectable plasma viral load, using standard clinical assays, have achieved full CD4+ lymphocyte recovery with normal levels of T cell activation and proliferation, and normal levels of immunoglobulins with no disease progression. It is anticipated that participants who have achieved a functional cure will continue to have detectable HIV-1 DNA in peripheral blood cells and/or tissues.
Number of participants who achieve a state of sterilizing cure Through 5 years after transplant -Sterilizing cure: same definition of functional cure but no detectable replication-competent virus in peripheral blood and minimal (near limits of detection) HIV-1 DNA in peripheral blood and or tissue
Number of participants who have plasma viral load <50 copies/ml Through 5 years after transplant -Obtained from peripheral blood
Number of participants who have gut immune reconstitution Through 5 years after transplant -Will consist of tissue immunohistochemistry to analyze CD4 T cells when feasible, and for plasma markers of gut microbial translocation namely lipopolysaccharide (LPS) and soluble CD14 (sCD14) a marker of monocyte activation attributed to LPS effects
Number of participants who have existence of replication competent HIV-1 reservoirs in peripheral blood, gut and other tissue compartments Through 5 years after transplant -Obtained from peripheral blood