In early trials of antiretroviral therapy, acyclovir was associated with increased survival by an unknown mechanism. The hypothesis that subclinical herpes simplex virus (HSV) reactivation was associated, in vivo, with increased plasma human immunodeficiency virus (HIV) RNA and suppression with a reduced plasma HIV RNA load was investigated. HSV cultures were performed daily on HSV-2-positive/HIV-positive patients, and plasma HIV-1 RNA loads were measured at regular intervals. A subset of patients prior to, during, and after HSV suppression with high-dose acyclovir was measured to determine whether HSV suppression was associated with a decrease in HIV replication. Most (25/27 HSV-2-positive/HIV-positive persons) reactivated HSV. Total HSV shedding rate was strongly correlated with plasma HIV-1 RNA load (R = 0.54; P = .004), and the plasma HIV-1 RNA level at a given CD4 cell count was 48% lower when treated with acyclovir. These data indicate that frequent mucosal HSV reactivation influences HIV replication in vivo and daily HSV suppression may be important in the management of HSV-positive/HIV-positive persons.
Bibliographical noteFunding Information:
Received 8 May 2002; revised 12 August 2002; electronically published 22 November 2002. The institutional review board of the University of Washington approved this study. Financial support: National Institutes of Health (grants AI30731 and AI01338) and the AIDS Clinical Trial Group (grant 2-U01-A127664-06). aPresent affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey. Reprints and correspondence: Dr. Timothy Schacker, Dept. of Medicine, University of Minnesota, Box 250, 516 Delaware St. SE, Minneapolis, MN 55455 (Schac008@tc.umn.edu).