To date, Berlin patient’s case provides the only evidence of long-term HIV-1 control after allogeneic stem cell transplantation (SCT), potentially due to the CCR5Δ32/Δ32 donor genotype. The case of the two Boston patients, without resulting in HIV cure, showed that the SCT procedure itself involves a tremendous reduction of the viral reservoir. The reason why this happened is unraveled yet. Herein we analyzed two patients from the European cohort EpiStem receiving different types of SCT
Patient 1 (Pt1) and Patient 3 (Pt3) were transplanted in 2012 and 2013 in Hospital Gregorio Marañón due to a Burkitt NHL and NK-NHL respectively. Analysis of the HIV-1 reservoir was performed 29 (Pt1) and 20 (Pt3) months post-transplant using qVOA, ddPCR, and semiquantitative PCR in CD4 T cells from peripheral blood and ileum, and CD3+ cells from bone marrow (BM). SCA was performed in plasma and CSF. Chimerism was performed by short tandem repeat PCR (STR-PCR). Antibody titers were determined by ELISA. Activation markers (CD38 and HLA-DR) were determined in CD4 and CD8 T-cells
Pt 1 received a myeloablative single cord blood SCT, supported with third party HLA-mismatched CD34+ cells (haplo-cord SCT). Pt 3 underwent reduced intensity conditioning SCT with peripheral blood progenitor cells (PBPC) of an HLA-matched sibling. Both patients were kept on cART. Donors were wt for CCR5. Pt 3 reached full chimera 1 month after SCT, while Pt 1 still harbors 0.2% of host cell in BM and 0.1% in PB. Pt 3 developed chronic GvH disease but not Pt 1. CD4 T cells from both patients were susceptible to in vitro R5 and X4-tropic HIV infection. IUPM in Pt 1 were 0.034 but undetectable (IUPM< 0.006) in Pt3. Total DNA in peripheral CD4 were 25 copies/106cells in Pt1, with 5 HIV RNA copies/ml in plasma. On the contrary, we were unable to detect virus in peripheral CD4, ileum CD4, BM, plasma or CSF in Pt3. Although both patients had a reduction in HIV-specific antibody titers, Pt 3 had lower levels. CD4 and CD8 activation levels were lower in Pt 3 than Pt 1
Within the EpiStem cohort, we compared two different SCT procedures, with different outcome regarding the viral reservoir. Allogeneic SCT with PBPC of an HLA-matched sibling donor, with a short engraftment time and a chronic GvH disease resulted in a more drastic reduction of the latent reservoir down to undetectable levels. We hypothesize that the “graft versus HIV-1 reservoir effect” contributes to facilitate the clearance of the viral reservoir