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Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals.

ABSTRACT: BACKGROUND:Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted. METHODS:We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4 T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4 T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period. RESULTS:All patients have been in continued remission for 4-6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir-related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT. CONCLUSIONS:These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes.

SUBMITTER: Koelsch KK

PROVIDER: S-EPMC6097982 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals.

Koelsch Kersten K KK Rasmussen Thomas A TA Hey-Nguyen William J WJ Pearson Chester C Xu Yin Y Bailey Michelle M Marks Katherine H KH Sasson Sarah C SC Taylor Mark S MS Tantau Robyn R Obeid Solange S Milner Brad B Morrissey Orla O Pinto Angie N AN Suzuki Kazuo K Busch Michael P MP Keating Sheila M SM Kaiser Philipp P Yukl Steven S Wong Joseph K JK Hiener Bonnie M BM Palmer Sarah S Zaunders John J Post Jeffrey J JJ Chan Derek J DJ Avery Sharon S Milliken Sam T ST Kelleher Anthony D AD Lewin Sharon R SR Cooper David A DA

Journal of acquired immune deficiency syndromes (1999) 20170701 3

<h4>Background</h4>Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted.<h4>Methods</h4>We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4 T-cell responses, HIV RNA, and DNA in plasm ...[more]

PMID: 28350553

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Project description:BACKGROUND: Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival. METHODS: The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. RESULTS: Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03). CONCLUSIONS: One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.

Dataset Information

Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals.

Publications

Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals.

Similar Datasets

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