Decreased HIV diversity after allogeneic stem cell transplantation of an HIV-1 infected patient: a case report

Abstract

The human immunodeficiency virus type 1 (HIV-1) coreceptor use and viral evolution were analyzed in blood samples from an HIV-1 infected patient undergoing allogeneic stem cell transplantation (SCT). Coreceptor use was predicted in silico from sequence data obtained from the third variable loop region of the viral envelope gene with two software tools. Viral diversity and evolution was evaluated on the same samples by Bayesian inference and maximum likelihood methods. In addition, phenotypic analysis was done by comparison of viral growth in peripheral blood mononuclear cells and in a CCR5 (R5)-deficient T-cell line which was controlled by a reporter assay confirming viral tropism. In silico coreceptor predictions did not match experimental determinations that showed a consistent R5 tropism. Anti-HIV directed antibodies could be detected before and after the SCT. These preexisting antibodies did not prevent viral rebound after the interruption of antiretroviral therapy during the SCT. Eventually, transplantation and readministration of anti-retroviral drugs lead to sustained increase in CD4 counts and decreased viral load to undetectable levels. Unexpectedly, viral diversity decreased after successful SCT. Our data evidence that only R5-tropic virus was found in the patient before and after transplantation. Therefore, blocking CCR5 receptor during stem cell transplantation might have had beneficial effects and this might apply to more patients undergoing allogeneic stem cell transplantation. Furthermore, we revealed a scenario of HIV-1 dynamic different from the commonly described ones. Analysis of viral evolution shows the decrease of viral diversity even during episodes with bursts in viral load.

Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART

“…In addition to the CCR5-null donor cells themselves, the preparative regimens administered prior to HCT likely ablated a proportion of latently-infected host CD4 + cells, and Grade I graft-versus-host disease (GVHD) may have further depleted the latent reservoir. 12,13 The most likely explanation is that a combination of these factors each contributed to the long-term, HAART-independent control of HIV-1 in this patient. 14 …”

Allogeneic haematopoietic stem cell transplantation in patients with human immunodeficiency virus: the experiences of more than 25 years

“…To analyse viral dynamics, they studied viral diversity and phylogeny by means of maximum likelihood and Bayesian methods. Interestingly, viral diversity decreased after HSCT, although the patient developed HIV rebound during a short period of HAART discontinuation [49].…”

Novel Cell and Gene Therapies for HIV

“…It is possible or even likely that the myeloablative therapy could have provided a synergistic effect. However, there are numerous reports of HIV-infected individuals undergoing allogeneic HSC or bone marrow transplants from donors not selected to be CCR5-negative, demonstrating that HIV-1 was not eliminated by the particular chemotherapy regimens used (Hassett et al 1983;Angelucci et al 1990;Bardini et al 1991;Schlegel et al 2000;Kang et al 2002;Avettand-Fenoel et al 2007;Wolf et al 2007;Woolfrey et al 2008;Kamp et al 2010;Polizzotto et al 2010), with one possible exception (Holland et al 1989). Of note, the Berlin patient's myeloablative therapy consisted of amsacrine, fludarabine, cytarabine, and cyclophosphamide, a regimen that has not previously been reported in patients with HIV infection.…”