(A) Longitudinal evolution of total B cells and indicated B cell subsets

(A) Longitudinal evolution of total B cells and indicated B cell subsets. who underwent allo-SCT for treatment of acute lymphoblastic leukemia. Methods and findings We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measuresincluding PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissuethe patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. Conclusions allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs. Author summary Why was this study done? Currently there is no cure for HIV infection. The only previously documented case of HIV cure occurred in the setting of stem cell transplantation for acute myeloid leukemia. However, other similar cases GNF-PF-3777 have not resulted in HIV cure. This observational study was done to further describe in detail the effects of allogeneic stem cell transplantation on residual HIV in a patient being treated for acute lymphoblastic leukemia. What did the researchers do and find? We prospectively collected blood and tissue GNF-PF-3777 samples from before and after stem cell transplantation and measured the HIV reservoir size using multiple complementary techniques. We found that the size of the HIV reservoir decreased substantially after transplantation to levels at or below the limit of detection BZS of most assays. We observed a prolonged remission from HIV rebound after antiretroviral treatment interruption in the post-transplant period. The genetic sequence of the rebounding virus in the blood clustered closely with sequences from blood prior to treatment interruption. What do these findings mean? These findings affirm that allogeneic stem cell transplantation can profoundly decrease the size of the HIV reservoir. However, current technologies for measuring reservoir size in blood are insufficiently sensitive to predict HIV cure. Until new biomarkers of HIV cure are developed, the decision to discontinue antiretroviral therapy after allogeneic stem cell transplantation to assess a possible cure should be undertaken cautiously. Introduction Since identification of the human immunodeficiency virus (HIV-1) as the causative agent for acquired immunodeficiency syndrome (AIDS), more than 70 million people have been infected, and an estimated 36 million people live with HIV-1 today [1]. Basic science advances in the GNF-PF-3777 understanding of HIV-1 have occurred at an unprecedented pace, allowing the development of numerous antiretroviral (ARV) agents, and advances in clinical science have determined optimal ways of using these drugs to reduce the morbidity and mortality associated with HIV-1 infection. Notwithstanding these impressive successes in the management of HIV-1, individuals who receive effective ARV therapy nonetheless have excess mortality compared to HIV-1 negative populations, due to the effects of inflammation and accelerated aging, manifested as increased risk of cardiovascular, metabolic, and malignant diseases [2]. Thus, a cure for HIV-1 infection is needed [3]. To date, GNF-PF-3777 only 1 1 case, known as the Berlin patient, has been cured of HIV-1 [4] by total myeloablative chemotherapy and total body GNF-PF-3777 irradiation treatment for acute myeloid leukemia, followed by 2 allogeneic stem cell transplants using cells from.