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No Viral Rebound After ART Stops in Two Stem-Cell Transplant Patients

Author: Mark Mascolini


05 July 2013

Viral load did not rebound 7 and 15 weeks after antiretroviral therapy (ART) stopped in two Boston men who had stem-cell transplants to treat lymphoma.

Clinician/researchers caring for the two men cautioned that the cases cannot be called cures yet, but discussion of the implications highlighted the final day of the 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention.

The cases invite comparison with the Berlin patient, a man cured of HIV infection after a stem-cell transplant. But management of the two Boston men differed from that of the Berlin patient in several important ways.

The Boston men were already taking combination ART when they were diagnosed with lymphoma. Both underwent reduced-intensity conditioning allogeneic hematopoetic stem cell transplantation (RIC-alloHSCT) with stem cells from donors who did not have the CCR5 delta 32 mutation, which largely protects T cells from HIV infection.

The men continued ART during their stem-cell transplants and for 2 and 5 years after the transplants. During continued ART, HIV could not be detected in plasma or peripheral blood mononuclear cells (PBMCs). Then clinicians asked the men if they would interrupt their ART under close observation, and both agreed.

Seven and 15 weeks after ART stopped, HIV did not reappear in PBMCs, and viral coculture could not detect HIV p24 antigen, a signal of viral replication, in purified CD4 cells. HIV DNA could not be detected in rectal tissue of one man. Neither man had detectable HIV-specific immune responses.

The Boston patients differ from the Berlin patient in that they had lymphoma and he had leukemia. The Berlin patient underwent total bone marrow obliteration before his stem-cell transplant, while the Boston men underwent only partial obliteration. The Berlin patient had stem cells transplanted from a donor carrying the rare CCR5 delta 32 mutation, which protects cells from HIV infection, whereas the Boston men had stem cells transplanted from donors with wild-type (nonmutated) CCR5. Finally, the Boston patients continued ART during their procedure and for years afterwards, while the Berlin patient did not.

Researchers speculate that continued ART protected newly created cells from HIV in the Boston men while graft-versus-host disease helped kill lingering pretransplant cells still infected with HIV.

Even if the Boston patients continue to remain free of HIV over the next months and years, this type of stem-cell transplant cannot be deployed in most other HIV-positive people. The procedures involved are expensive and very risky, carrying a 15% to 20% risk of death, and are appropriate only for people gravely ill with a cancer that responds to stem-cell transplantation.

Sources:

T. Henrich, E. Hanhauser, M. Sirignano, et al. In depth investigation of peripheral and gut HIV-1 reservoirs, HIV-specific cellular immunity, and host microchimerism following allogeneic hematopoetic stem cell transplantation. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract WELBA05.

Donald G. McNeil Jr. Post-transplant and off drugs, H.I.V. patients are apparently virus-free. New York Times. 3 July 2013.

For an IAS 2013 press conference on the Boston cases

For the New York Times article