Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment

Martha C Nason; Eshan U Patel; Allison R Kirkpatrick; Jessica L Prodger; Kamnoosh Shahabi; Aaron A R Tobian; Sara Gianella; Sarah Kalibbala; Paschal Ssebbowa; Rupert Kaul; Ronald H Gray; Thomas C Quinn; David Serwadda; Steven J Reynolds; Andrew D Redd

doi:10.1093/ofid/ofw073

Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment

Open Forum Infect Dis. 2016 Apr 6;3(2):ofw073. doi: 10.1093/ofid/ofw073. eCollection 2016 Mar.

Authors

Affiliations

¹ Biostatistics Research Branch , National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) .
² Laboratory of Immunoregulation , NIAID, NIH , Baltimore, Maryland.
³ Department of Infectious Diseases , University of Toronto , Canada.
⁴ Department of Pathology, Johns Hopkins Hospital; Department of Epidemiology, Bloomberg School of Public Health.
⁵ Department of Infectious Disease , University of California San Diego , La Jolla.
⁶ Rakai Health Sciences Program , Entebbe.
⁷ Department of Epidemiology, Bloomberg School of Public Health; Rakai Health Sciences Program, Entebbe.
⁸ Laboratory of Immunoregulation, NIAID, NIH, Baltimore, Maryland; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
⁹ Rakai Health Sciences Program, Entebbe; School of Public Health, Makerere University, Kampala, Uganda.
¹⁰ Laboratory of Immunoregulation, NIAID, NIH, Baltimore, Maryland; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland; Rakai Health Sciences Program, Entebbe.

Abstract

Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation.

Keywords: CMV; Cytokine; HIV; HSV-2; viral shedding.

Abstract

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