title: Changes in plasma human immunodeficiency virus type 1 RNA associated with herpes simplex virus reactivation and suppression.
abstract: 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.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, 55455, USA. Schac008@tc.umn.edu
authors.forename: Timothy
authors.initials: T
authors.lastname: Schacker
authors.forename: Judith
authors.initials: J
authors.lastname: Zeh
authors.forename: Huilin
authors.initials: H
authors.lastname: Hu
authors.forename: Mary
authors.initials: M
authors.lastname: Shaughnessy
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006558:Herpes Genitalis / Q000097:blood / Q000150:complications / Q000821:virology; D006561:Herpes Simplex / Q000097:blood / Q000150:complications / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D018139:Simplexvirus / Q000187:drug effects / Q000302:isolation & purification* / Q000502:physiology; D013997:Time Factors; D014775:Virus Activation / Q000187:drug effects*; D017201:Virus Shedding
chemical_list: D000998:Antiviral Agents; D015483:HIV Antibodies; D012367:RNA, Viral; D000212:Acyclovir