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Increase in HSV shedding at initiation of antiretroviral therapy and decrease in shedding over time on antiretroviral therapy in HIV and HSV-2 infected persons

Ford, Emily S.a,e; Magaret, Amalia S.b,c,e; Spak, Cedric W.f,g; Selke, Stacyb; Kuntz, Steveb; Corey, Lawrencea,b,e; Wald, Annaa,b,d,e

doi: 10.1097/QAD.0000000000002002

Objectives: HIV-infected persons with chronic herpesvirus infections may experience paradoxical worsening after initiation of antiretroviral therapy (ART), but the impact of longer term ART is unclear. We evaluated the relationships between genital herpes simplex virus (HSV) shedding and ART initiation and time on therapy in HIV and HSV-2-infected persons.

Design: Prospective observational study.

Methods: Rates of HSV shedding in 45 HIV and HSV-2-infected persons on or off ART were prospectively followed over up to three, noncontiguous, 60-day periods, during which participants performed daily genital swabs for HSV detection by real-time HSV DNA PCR and reported symptoms. Initiation or discontinuation of ART was at the discretion of participants’ healthcare providers.

Results: In all, 6425 daily genital swabs were obtained from 45 persons (38 men and seven women) during 105 swabbing sessions. During the three sessions, 67, 74, and 92% of persons were on ART. HSV was detected on 26.5% of days in men and 22.3% of days in women. The overall rates of genital HSV shedding were 19.4% of days in persons not on ART, 30.2% in persons within 90 days of ART initiation, and 23.3% in persons on ART for longer than 90 days. After initiation of ART, HSV shedding decreased by 2% per month, or 23% per year (RR 0.98/month on ART; P = 0.0003 in adjusted analysis). This finding was consistent after including consideration of HIV viral load and CD4+ cell count.

Conclusions: HSV shedding increased significantly shortly after ART initiation, but decreased with time on prolonged ART.

aDepartment of Medicine

bDepartment of Laboratory Medicine

cDepartment of Biostatistics

dDepartment of Epidemiology, University of Washington

eVaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle Washington

fSimmons Transplant Institute, Dallas

gBaylor All Saints Medical Center, Fort Worth, Texas, USA.

Correspondence to Emily S. Ford, 1100 Eastlake Avenue East, Seattle, WA 98109, USA. Tel: +1 206 667 7315; fax: +1 206 667 6179; e-mail:

Received 23 May, 2018

Accepted 12 August, 2018

Copyright © 2018 Wolters Kluwer Health, Inc.