Valacyclovir decreases plasma and genital viral loads in HSV-2/HIV-1 co-infected women
Polly Clayden, HIV i-Base
A poster authored by Jared Baeten and coworkers from the University of Washington, Seattle, US; Assn Civil Impacta Salud y Educacion, Lima, Peru; and Fred Hutchinson Cancer Reserach Centre, Seattle, WA, US showed findings from a study to assess whether HSV-2 suppressive therapy reduces HIV-1 plasma and genital viral loads. 
This was a randomised, placebo-controlled, cross-over trial of 500 mg valacyclovir received orally twice daily by 20 HSV-2/HIV-1 co-infected women in Lima, Peru who had CD4 counts >200 cells/mm3 and were not receiving ART.
The women were randomised to receive valacyclovir or placebo for 8 weeks. Then following a 2-week washout period, they received the alternative regimen for a further 8 weeks.
Plasma samples were taken weekly and endocervical swabs were collected three times a week for measurement of HIV-1 viral load. Additionally, the women collected genital swabs themselves daily for HSV DNA PCR. The women’s median CD4 count was 372 cells/mL (range 229- 850).
The investigators reported detection of genital HSV on 3.7% of days receiving valacyclovir versus 22.1% of days receiving placebo (p<0.001). HIV-1 plasma viral load was significantly lower during the valacyclovir arm compared to the placebo arm, 4.34 vs 4.61 log copies/mL, p<0.001; a difference of -0.27 log copies/mL, (95%CI -0.34 to -0.20). Cervical HIV-1 was detected at 54.3% of visits while receiving valacyclovir versus 71.1% of visits while receiving placebo, p<0.001. Cervical HIV-1 levels were significantly lower while receiving valacyclovir vs placebo, 2.87 vs 3.23 log copies/swab, p<0.001; a difference of –0.35 log copies/swab, (95% CI –0.46 to –0.25).
The investigators concluded: “Daily valacyclovir therapy (500 mg twice daily) for HSV-2 suppression significantly reduced plasma and genital HIV-1 concentrations among HSV-2/HIV-1 co-infected women. Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and the rate of disease progression; these outcomes are under evaluation in ongoing clinical trials.”
Results from the HPTN 039 study conducted by the same group were also presented at this conference . This was a randomised, placebo-controlled trial to determine whether HSV-2 suppression with twice-daily acyclovir reduces the risk of HIV acquisition among women in Africa and men who have sex with men (MSM) in the Americas (n=3251).
This study found that acyclovir did not reduce HIV acquisition among women with HSV-2 and MSM, despite evidence from multiple epidemiologic studies that HSV-2 infection increases HIV susceptibility by 2- to 3-fold, even with excellent retention and adherence among the trial participants. The investigators wrote “..acyclovir (400 mg twice daily) suppresses HSV-2, but does not prevent HIV acquisition. Further research is needed to elucidate the disparity between extensive data on epidemiologic and biologic interactions between HSV-2 and HIV and these trial results.”
Although the investigators suggest that suppressive HSV-2 therapy with valganciclovir has the potential to reduce HIV-1 infectiousness and the rate of disease progression, the results from ongoing research with valganiclovir are needed
1. Baeten J, Strick L, Lucchetti A et al. Herpes simplex virus suppressive treatment decreases plasma and genital HIV-1 viral loads in HSV-2/HIV-1 co-infected women: A randomised, placebo-controlled, cross-over trial 15th CROI. February 2008. Boston, US. Poster abstract 676.
2. Celum C, Wald A, Hughes J et al., HSV-2 suppressive therapy for prevention of HIV acquisition: Results of HPTN 039. 15th CROI. February 2008. Boston, US. Oral abstract 32.