Allogeneic Hematopoietic Stem Cell Transplant Reduces HIV Reservoir

For patients with HIV, allogeneic hematopoietic stem cell transplant leads to a long-term reduction in the HIV reservoir, according to results published in the Annals of Internal Medicine.

The results indicate that factors including stem cell source, conditioning, and a graft-versus-HIV-reservoir effect may have contributed to this reduction. The researchers noted that understanding what mechanisms underlie HIV eradication after allogeneic hematopoietic stem cell transplant may lead to the development of new curative strategies.

The study included participants with HIV who were treated with antiretrovirals and had survived more than 2 years after allogeneic hematopoietic stem cell transplant with CCR5 wild-type donor cells (n=6). The researchers performed HIV DNA analysis, HIV RNA analysis, and quantitative viral outgrowth assay in blood. They also measured HIV DNA in lymph nodes, ilea, bone marrow, and cerebrospinal fluid. The researchers used a humanized mouse model for in vivo detection of the replication-competent blood cell reservoir. They used plasma to measure HIV-specific antibodies.

After analyzing the viral reservoir, 5 participants had full-donor chimera in T cells within 1 year after transplant, undetectable proviral HIV DNA in blood and tissue, and undetectable replication-competent virus (<0.006 infectious unit/million cells).

Only 1 participant had detectable viral infection. This participant had received cord blood stem cells with an antithymocyte globulin-containing conditioning regimen, did not develop graft-versus-host disease, and had delayed complete standard chimerism in T cells with mixed ultrasensitive chimera.

When the researchers performed an adoptive transfer of peripheral CD4⁺ T cells to immunosuppressed mice, there was no viral rebound. In addition, HIV antibody levels decreased over time, with the exception of 1 case of seroreversion.

The researchers noted that the small number of participants in their study is a significant limitation.

“Further studies are needed to confirm that a graft-versus-HIV-reservoir effect might be key to achieving a sterilizing cure after [allogeneic hematopoietic stem cell transplant] in HIV-infected persons,” the researchers wrote.

Reference

Salgado M, Kwon M, Galvez C, et al. Mechanisms that contribute to a profound reduction of the HIV-1 reservoir after allogenic stem cell transplant [published online October 16, 2018]. Ann Intern Med. doi: 10.7326/M18-0759