730. Safety of optimized antiretroviral therapy during allogeneic matched and haploidentical bone marrow transplant in HIV+ individuals
Session: Oral Abstract Session: Antiretroviral Therapy: New Drugs and Treatment Outcomes
Friday, October 9, 2015: 11:45 AM
Room: 25--ABC
Background: The latent HIV reservoir in hematopoietic cells is a barrier to cure. With allogeneic bone marrow transplant (alloBMT), hematopoietic cells are replaced with donor cells due to graft versus host effects. Antiretroviral therapy (ART) should protect donor cells from infection and result in HIV reservoir reduction.  However, ART is often interrupted during alloBMT due to drug interactions, mucositis and vomiting or organ dysfunction.

Methods: We evaluated the safety and feasibility of continuing ART during alloBMT in HIV+ individuals with hematologic malignancy. Optimized ART included: 1) avoidance of ritonavir to minimize drug interactions 2) ART changes for organ dysfunction 3) subcutaneous enfurvirtide (ENF) during post-transplant cyclophosphamide and if oral ART was not tolerated. Primary endpoints included adverse events (AE) from ENF and maintenance of ART through day 60.  Donor chimerism and HIV- infected cells per million (IUPM) by viral outgrowth assay were measured.  

Results: 6 individuals received alloBMT, including 2 cases of haploidentical transplants.   There were no AEs due to ENF.  All patients required ART changes but maintained ART through day 60. Patient 3 was non-adherent with ART at month 5 and had HIV rebound and meningoencephalitis.
Patient ID 1 2 3 4 6 7
Cancer Hodgkin Non-Hodgkin AML AML Non-Hodgkin Hodgkin
Transplant Type MUD MUD MRD MRD Haploidentical Haploidentical
Pre alloBMT Viral Load (c/ml) 79 <20 <20 <20 <20 21
Post alloBMT HIV IUPM (*p24-) ≤ 0.088* (week 24) ≤ 0.187* (week 90) ND 0.45 (week 48) ≤ 0.073* (week 12) ND
PBMC Donor Chimerism (%) >95 87 >95 58 >95 >95
# of ART Changes 6 2 2 5 2 3
Survival Died week 49, liver failure Remission week 101 Died week 64, graft vs host disease Remission week 48 Alive week 20 Alive week 10

Conclusion: During alloBMT, it is feasible to maintain ART including injectable ENF but ART changes are needed. At early time-points, with mixed chimerism, HIV persists.  Interruption of ART during alloBMT can cause a severe acute retroviral syndrome likely due to lack of any immune response from HIV-naïve donor cells.  Novel strategies are needed in combination with alloBMT to provide HIV remission and protective immunity for donor cells.

Ayla Cash, MPH1, Adam Capoferri, B.Sc.1,2, Daniel Xu, B.Sc.1, Holly Mchugh, ScM1, Oliver Laeyendecker, PhD1,3, Sarah Sakoian, RN4, Lori Tony, RN4, Cynthia Bullen, PhD1, Christopher Pohlmeyer, B.Sc.1, Paul Pham, PharmD, BCPS1,5, Jun Lai, B.A.1, Joel Gallant, MD, MPH, FIDSA6, Robert Siliciano, MD, PhD1,2, Charles Flexner, MD1, Keith Pratz, MD4, Mark Levis, MD4, Richard Jones, MD4, Yvette Kasamon, MD4, Richard Ambinder, MD, PhD4 and Christine Durand, MD1,4, (1)Johns Hopkins University Department of Medicine, Baltimore, MD, (2)Howard Hughes Medical Institute, Baltimore, MD, (3)National Institute of Allergy and Infectious Diseases, Bethesda, MD, (4)Johns Hopkins University Sidney Kimmel Cancer Center, Baltimore, MD, (5)Johns Hopkins University Department of Pharmacy, Baltimore, MD, (6)Southwest CARE Center, Santa Fe, NM

Disclosures:

A. Cash, None

A. Capoferri, None

D. Xu, None

H. Mchugh, None

O. Laeyendecker, None

S. Sakoian, None

L. Tony, None

C. Bullen, None

C. Pohlmeyer, None

P. Pham, None

J. Lai, None

J. Gallant, AbbVie: Investigator , Research support
Bristol-Myers Squibb: Investigator and Scientific Advisor , Consulting fee and Research support
Gilead Sciences: Investigator and Scientific Advisor , Consulting fee and Research support
Janssen Therapeutics: Investigator and Scientific Advisor , Consulting fee and Research support
Merck & Co.: Investigator and Scientific Advisor , Consulting fee and Research support
Sangamo BioSciences: Investigator , Research support
ViiV Healthcare: Investigator and Scientific Advisor , Consulting fee and Research support

R. Siliciano, None

C. Flexner, None

K. Pratz, None

M. Levis, None

R. Jones, None

Y. Kasamon, None

R. Ambinder, None

C. Durand, Gilead Sciences: Scientific Advisor , Research grant

<< Previous Abstract | Next Abstract

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.