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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
-Accepted tool in the evaluation of immunological interventions, gene therapy, or therapeutic vaccines for the treatment of HIV infection
-Screening, entry for Step 1, Step 1 visit 2, entry for Step 2, weekly, week 16, monthly through week 52, week 52, quarterly through year 5, year 5, and viral relapse
HIV-1 proviral DNA levels in peripheral blood
* Obtained from peripheral blood * Used to determine if participant can proceed to Step 2
Time frame: Up to week 16 after transplant
HIV-1 reactivation in stimulated assay
* Obtained from peripheral blood * Used to determine if participant can proceed to Step 2
Time frame: Up to week 16 after transplant
Presence and severity of GvHD
-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
Time frame: Through 5 years after transplant
Time to hematopoietic cell and immune recovery
-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.
Time frame: Up to 100 days after transplant
Number of participants who experience chimerism
-Chimerism is measured by ≥ 98% of blood cells donor derived
Time frame: At the time of screening
Survival of participants
-Number of participants who are alive 100 days after transplant
Time frame: 100 days after transplant
Survival of participants
-Number of participants who are alive 26 weeks after transplant
Time frame: Week 26 after transplant
Survival of participants
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-Number of participants who are alive 52 weeks after transplant
Time frame: Week 52 after transplant
Survival of participants
-Number of participants who are alive 5 years after transplant
Time frame: 5 years after transplant
Event free survival
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
Time frame: 100 days after transplant
Event free survival
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
Time frame: Week 26 after transplant
Event free survival
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
Time frame: Week 52 after transplant
Event free survival
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
Time frame: 5 years after transplant
Number of participants who achieve a state of functional cure
-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.
Time frame: Through 5 years after transplant
Number of participants who achieve a state of sterilizing cure
-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
Time frame: Through 5 years after transplant
Number of participants who have plasma viral load <50 copies/ml
-Obtained from peripheral blood
Time frame: Through 5 years after transplant
Number of participants who have existence of replication competent HIV-1 reservoirs in peripheral blood, gut and other tissue compartments
-Obtained from peripheral blood
Time frame: Through 5 years after transplant
Number of participants who have gut immune reconstitution
-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
Time frame: Through 5 years after transplant