HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men

Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
AIDS (London, England) (Impact Factor: 5.55). 02/2009; 23(4):479-83. DOI: 10.1097/QAD.0b013e328326ca62
Source: PubMed


Suppressive herpes simplex virus (HSV) therapy can decrease plasma, cervical, and rectal HIV-1 levels in HIV-1/HSV-2 co-infected persons. We evaluated the effect of HSV-2 suppression on seminal HIV-1 levels.
Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2 men who have sex with men (MSM) in Lima, Peru, with CD4 >200 cells/microl randomly received valacyclovir 500 mg twice daily or placebo for 8 weeks, then the alternative regimen for 8 weeks after a 2-week washout. Peripheral blood and semen specimens were collected weekly. Anogenital swab specimens for HSV DNA were self-collected daily and during clinic visits.
HIV-1 RNA was quantified in seminal and blood plasma by TaqMan real-time polymerase chain reaction (RT-PCR) or Roche Amplicor Monitor assays. HSV and seminal cytomegalovirus (CMV) were quantified by RT-PCR. Linear mixed models examined differences within participants by treatment arm.
Median CD4 cell count of participants was 424 cells/microl. HIV-1 was detected in 71% of 231 semen specimens. HSV was detected from 29 and 4.4% of swabs on placebo and valacyclovir, respectively (P < 0.001). Valacyclovir significantly reduced the proportion of days with detectable seminal HIV-1 (63% during valacyclovir vs. 78% during placebo; P = 0.04). Seminal HIV-1 quantity was 0.25 log10 copies/ml lower [95% confidence interval (CI) -0.40 to -0.10; P = 0.001] during the valacyclovir arm compared with placebo, a 44% reduction. CD4 cell count (P = 0.32) and seminal cellular CMV quantity (P = 0.68) did not predict seminal plasma HIV-1 level.
Suppressive valacyclovir reduced seminal HIV-1 levels in HIV-1/HSV-2 co-infected MSM not receiving ART. The significance of this finding will be evaluated in a trial with HIV-1 transmission as the outcome.

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    • "Most commonly, HSV-1 causes oral and genital sores, but HSV-2 is the most common cause of genital herpes. Generally, direct or indirect contact with herpetic lesions is infectious, but HSV-1 and HSV-2 have been detected in semen [22], [55] and in sperm, and HSV-2 has been transmitted through donor insemination [56], [57]. DNA of HSV-1 and HSV-2 has been detected in the semen from 2-50% of men with no significant difference between fertile and infertile subjects [22], [56], [58]. "
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    • "In a prior study in the Gambia, maternal genital shedding of CMV was associated with both congenital and early infant infections [5]. Few studies have examined effects of antiviral therapy on CMV levels in the genital tract; an RCT in HIV-1-infected men found no effect of 500 mg twice daily valacyclovir on semen CMV levels [20]. In our placebo arm, cervical CMV shedding increased between 34 and 38 weeks, consistent with reports of increased shedding during late pregnancy [21], but this increase was attenuated in the valacyclovir arm. "
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    • "The research found that 1) HSV-2 episodic therapy was marginally beneficial in some, but not all patient groups and settings, in terms of ulcer healing and reduction of HIV levels in the genital tract [24-26]; 2) HSV-2 suppressive therapy did not appear to prevent HIV acquisition in two large trials [27,28]; 3) HSV-2 suppressive therapy generally decreased HIV levels in plasma and genital secretions in most studies [10,13,29-33]; but 4) this was not enough to decrease HIV transmission between partners in HIV serodiscordant couples [34] (this final landmark study ended one year after the Montreux meeting and was published two years later). Despite these globally disappointing results, a recommendation was made during the Expert Meeting to modify the WHO GUD syndromic management guidelines to include anti-herpetic therapy in the syndromic management cocktail, without a prevalence threshold. "
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