CCR5Δ32Δ32 Haplo-cord transplant leads to HIV-1 remission

In the 2022 Conference on Retroviruses and Opportunistic Infections (CROI), Dr. Yvonne Bryson from the School of Medicine at UCLA and Mattel Children’s Hospital in California, the United States (US), discussed a human immunodeficiency virus-1 (HIV-1) remission case using CCR5Δ32Δ32 Haplo-cord transplant in a US woman.1

Currently, there have been 2 cases of HIV-1 cure involving a Berlin patient (2009) and a London patient (2019).1 Both patients had cancers that required transplant and received adult cells from bone marrow (BM) or peripheral CCR5Δ32Δ32 cells, which are resistant to HIV.1 Remission was observed at 20 months in the Berlin patient for more than 12 years and at 18 months in the London patient for more than 30 months, and both were deemed cured.1

The reasons behind only 2 cases of HIV-1 cure with transplantation are the rare presence of CCR5Δ32Δ32 cell mutation and its occurrence mainly in Europe without a routine screening of BM or donors, making it difficult to identify the mutations.1 Besides, adult unrelated donor grafts allow rapid engraftment with a high cell dose, but require a stringent human leukocyte antigen (HLA) match to avoid graft versus host disease (GVHD).1 In contrast, umbilical cord blood grafts are readily available due to cord blood banks with less stringent HLA match but provide a low cell dose, delaying engraftment.1 Hence, a potential solution would be combining haploidentical cord grafts, which could accelerate engraftment using adult graft until cord graft is ready.1

This technique was adopted in the IMPAACT P1107 study presented.1 This observational study used cord blood transplantation with CCR5Δ32Δ32 donor cells in HIV children and adults who require transplantation due to other underlying conditions such as cancer or hematopoietic diseases, while previously screened cord blood units were used for transplantation.1 The laboratory studies used to examine HIV-1 persistence included chimerism, antiretroviral drug levels, HIV-1 cellular immune responses, biomarkers, and antibody responses.1 A unique case report of a female with HIV-1 and high risk of acute myeloid leukemia (AML) monosomy 7 receiving a partially matched (5/8) CCR5Δ32Δ32 haplo transplant and relative peripheral blood mononuclear cell (PBMC) was presented.1

Throughout the treatment course, plasma viral load was undetectable with a decrease in immune activation of CD4 and CD8 T cells.1 Additionally, HIV-1 antigen (HIV-1 gag)-specific T cells were not detected, while polyclonal responses (SEB) were intact.1 Viral studies, including deoxyribonucleic acid (DNA), transrenal DNA, replication, and plasma viral load, became negative post-transplant after being positive pre-transplant.1 Moreover, a loss of HIV-1 specific antibody responses was detected by week 55 post-transplant.1

In conclusion, this was the first US HIV woman successfully transplanted with CCR5Δ32Δ32 haplo-cord stem cell transplant, in addition to a 100% sustained engraftment of cord blood demonstrating HIV-1 remission and a durable AML remission.1 She has not been on any antiretroviral for 14 months with no signs of viral rebound, detectable replication-competent latent reservoir, HIV-1 specific cellular immune responses antibodies, or GVHD.1 This study showed a potential for the use of cord blood cells or haplo cord to achieve HIV-1 remission in patients requiring transplantation for other diseases.1 Further studies are needed to support that HIV-1 reservoirs can be cleared sufficiently for remission or cure in the resistant target cells.1

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