title: Treatment with valacyclovir, famciclovir, or antiretrovirals reduces human herpesvirus-8 replication in HIV-1 seropositive men.
abstract: Human herpesvirus-8 (HHV-8) replication is a key factor in Kaposi sarcoma, primary effusion lymphoma, and Castleman disease pathogenesis. In vitro data suggest that antivirals inhibit HHV-8 replication, but little data exist in humans. Daily oropharyngeal swabs were analyzed from HIV/HHV-8 dually infected men enrolled in three previous clinical trials of valacyclovir and famciclovir for HIV-1 and/or HSV-2 suppression. Fifty-eight participants contributed 6,036 swabs. HHV-8 was detected in 1,128 (19%) of 6,036 swabs, including 618 (21%) of 2,992 on placebo, 323 (15%) of 2,221 on valacyclovir, and 187 (23%) of 823 on famciclovir. After adjusting for baseline HIV viral load and highly active antiretroviral therapy (HAART) use, an 18% reduction in HHV-8 shedding frequency (IRR 0.822; P = 0.011) was found in participants on valacyclovir and a 30% reduction (IRR 0.700; P < 0.001) on famciclovir. HAART was associated with an 89% (IRR 0.129; P = 0.048) reduction in HHV-8-shedding. Neither antiviral nor antiretroviral therapy was associated with decreased HHV-8 quantity. Valacyclovir and famciclovir were associated with modest but significant reductions in HHV-8 oropharyngeal shedding frequency. In contrast, HAART was a potent inhibitor of HHV-8 replication. Studies of whether antiviral therapy in combination with ART will prevent HHV-8-associated disease appear warranted.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Cattamanchi
authors.forename: Misty
authors.initials: M
authors.lastname: Saracino
authors.forename: Stacy
authors.initials: S
authors.lastname: Selke
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Corey
authors.initials: C
authors.lastname: Casper
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000821:virology; D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077595:Famciclovir; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009960:Oropharynx / Q000821:virology; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015075:2-Aminopurine; D014633:Valine; D000077483:Valacyclovir; D000077595:Famciclovir; D000212:Acyclovir