Treatment with valacyclovir, famciclovir, or antiretrovirals reduces human herpesvirus-8 replication in HIV-1 seropositive men

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. J. Med. Virol. 83:1696–1703, 2011. © 2011 Wiley‐Liss, Inc.