Herpes Simplex Virus Suppressive Therapy in Herpes Simplex Virus-2/Human Immunodeficiency Virus-1 Coinfected Women Is Associated With Reduced Systemic CXCL10 But Not Genital Cytokines.
Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with HSV-2 and HIV-1 was conducted and HSV-2 suppression was found to significantly reduce both HSV-2 and HIV-1 viral loads both systemically and the endocervical compartment.



To determine the effect of HSV-2 suppression on systemic and genital mucosal inflammation, plasma specimens, and endocervical swabs were collected weekly from volunteers in the trial and cryopreserved. Plasma was assessed for concentrations of 31 cytokines and chemokines; endocervical fluid was eluted from swabs and assayed for 14 cytokines and chemokines.



Valacyclovir significantly reduced plasma CXCL10 but did not significantly alter other cytokine concentrations in either compartment.



These data suggest genital tract inflammation in women persists despite HSV-2 suppression, supporting the lack of effect on transmission seen in large scale efficacy trials. Alternative therapies are needed to reduce persistent mucosal inflammation that may enhance transmission of HSV-2 and HIV-1.
From the *Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of †Global Health, ‡Medicine, §Epidemiology and ∥Laboratory Medicine, University of Washington, Seattle, WA; and ¶Investigaciones Medicas en Salud (INMENSA), Lima, Peru.
Erica
E
Andersen-Nissen
Joanne T
JT
Chang
Katherine K
KK
Thomas
Devin
D
Adams
Connie
C
Celum
Jorge
J
Sanchez
Robert W
RW
Coombs
M Juliana
MJ
McElrath
Jared M
JM
Baeten
D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D054357:Chemokine CXCL10 / Q000378:metabolism*; D060085:Coinfection; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D060737:Reproductive Tract Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
D000998:Antiviral Agents; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir