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1.
Clin Infect Dis ; 63(8): 999-1006, 2016 10 15.
Article in English | MEDLINE | ID: mdl-27481873

ABSTRACT

BACKGROUND: Respiratory viral infections (RVIs) are frequent complications of hematopoietic stem cell transplant (HSCT). Surgical masks are a simple and inexpensive intervention that may reduce nosocomial spread. METHODS: In this prospective single-center study, we instituted a universal surgical mask policy requiring all individuals with direct contact with HSCT patients to wear a surgical mask, regardless of symptoms or season. The primary endpoint was the incidence of RVIs in the mask period (2010-2014) compared with the premask period (2003-2009). RESULTS: RVIs decreased from 10.3% (95/920 patients) in the premask period to 4.4% (40/911) in the mask period (P < .001). Significant decreases occurred after both allogeneic (64/378 [16.9%] to 24/289 [8.3%], P = .001) and autologous (31/542 [5.7%] to 16/622 [2.6%], P = .007) transplants. After adjusting for multiple covariates including season and year in a segmented longitudinal analysis, the decrease in RVIs remained significant, with risk of RVI of 0.4 in patients in the mask group compared with the premask group (0.19-0.85, P = .02). In contrast, no decrease was observed during this same period in an adjacent hematologic malignancy unit, which followed the same infection control practices except for the mask policy. The majority of this decrease was in parainfluenza virus 3 (PIV3) (8.3% to 2.2%, P < .001). CONCLUSIONS: Requiring all individuals with direct patient contact to wear a surgical mask is associated with a reduction in RVIs, particularly PIV3, during the most vulnerable period following HSCT.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Infection Control , Masks , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , Adolescent , Adult , Aged , Aged, 80 and over , Confounding Factors, Epidemiologic , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Humans , Immunocompromised Host , Incidence , Infection Control/methods , Male , Middle Aged , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Seasons , Young Adult
2.
J Clin Invest ; 125(11): 4077-90, 2015 Nov 02.
Article in English | MEDLINE | ID: mdl-26413868

ABSTRACT

Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell-mediated clearance of HIV-1-infected cells. Specifically, we employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity-mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells (referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells to specifically engage with and kill Env-expressing cells, including CD4+ T cells infected with different HIV-1 subtypes, thereby obviating the requirement for HIV-specific immunity. Using lymphocytes from patients on suppressive antiretroviral therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T cells that are superinfected with the HIV-1 strain JR-CSF or infected with autologous reservoir viruses isolated from HIV-infected-patient resting CD4+ T cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T cell cultures following induction of latent virus expression. Combined with HIV latency reversing agents, HIVxCD3 DARTs have the potential to be effective immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected individuals.


Subject(s)
Antibodies, Bispecific/immunology , CD4-Positive T-Lymphocytes/virology , HIV Antibodies/immunology , HIV Envelope Protein gp120/immunology , HIV Envelope Protein gp41/immunology , HIV Infections/immunology , HIV-1/immunology , Immunotherapy/methods , T-Lymphocytes, Cytotoxic/immunology , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , CD4-Positive T-Lymphocytes/immunology , Genes, Reporter , HIV Infections/drug therapy , Humans , Jurkat Cells , T-Cell Antigen Receptor Specificity , Virus Activation/immunology , Virus Latency
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