CFAR Awards

Christine Durand, MD

Infectious Diseases, Johns Hopkins School of Medicine

Optimized antiretroviral therapy during allogeneic hematopoietic stem cell transplant in HIV-1 infection

Christine Durand, MD - Image

The major obstacle to HIV-1 cure in individuals on antiretroviral therapy (ART) is a reservoir of latently-infected memory CD4+ T-cells.  There is interest in the potential of allogeneic hematopoietic stem cell transplant (alloHSCT) to eradicate HIV-1 infection.  In the process of alloHSCT, donor lymphocytes eliminate host hematopoietic cells over weeks to months due to the “allogeneic effect” or graft-versus-host effect.  If HIV-1 persists only in hematopoietic cells, all host HIV-1 reservoirs should be eliminated with successful alloHSCT.  In parallel, continued ART should protect donor cells from acquiring HIV-1, just as ART prevents HIV-1 infection in utero or after high-risk exposure.   In clinical practice, ART is often interrupted due to drug interactions, or mucositis, nausea, and vomiting related to chemotherapy.  We will evaluate a strategy of optimized ART to prevent interruptions in HIV-1-infected patients with hematologic malignancies who require alloHSCT.  This strategy will include: 1) a multidisciplinary team that will select an ART regimen that minimizes drug interactions and includes agents with long half-lives to maximize antiviral activity in the event of missed doses, 2) the addition of subcutaneous enfuvirtide, (the only non-oral formulation antiretroviral without bone marrow toxicity) during high-risk periods of nausea and vomiting, and 3) directly-observed ART during the first month of alloHSCT, and adherence monitoring for 6 months after transplant.  We will evaluate the impact of this strategy on ART interruptions and HIV-1 reservoirs.