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Herpes Simplex Virus Suppressive Treatment Decreases Plasma and Genital HIV-1 Viral Loads in HSV-2/HIV-1 Co-infected Women: A Randomized, Placebo-controlled, Cross-over Trial
Jared Baeten*1, L Strick1, A Lucchetti2, W Whittington1, J Sanchez2, R Coombs1, A Magaret1, A Wald1,3, L Corey1,3, and C Celum1
1Univ of Washington, Seattle, US; 2Assn Civil Impacta Salud y Educacion, Lima, Peru; and 3Fred Hutchinson Cancer Res Ctr, Seattle, WA, US
Background: Herpes simplex virus type 2 (HSV-2) is a
common co-infection (50 to 90% prevalence in most populations) among persons
with HIV-1. Observational studies have found HSV-2 reactivation to be
associated with higher HIV-1 plasma and genital viral loads, suggesting that
HSV-2 may increase HIV-1 infectiousness and accelerate disease progression. Our
objective was to assess whether HSV-2 suppressive therapy reduces HIV-1 plasma
and genital levels.
Methods: We conducted a randomized,
placebo-controlled, cross-over trial of HSV-2 suppressive therapy using
valacyclovir 500 mg orally twice daily among 20 HSV-2/HIV-1 co-infected women in
Lima, Peru who had CD4 counts >200 cells/µL and were not on ART. Participants
were randomly assigned to receive valacyclovir or placebo for 8 weeks, then
after a 2-week washout period, to receive the alternative regimen for an
additional 8 weeks. Plasma was collected weekly and endocervical swabs were
collected thrice weekly for measurement of HIV-1 RNA levels, performed by Taqman
rt-PCR; genital swabs for HSV DNA PCR were self-collected daily. Linear
mixed-effects analysis and generalized estimating equations were used to
compare the effect of valacyclovir versus placebo on plasma and genital HIV-1 levels
and genital HSV detection.
Results: Median CD4 count was 372 cells/mL (range 229 to 850). Genital HSV was
detected on 4% of days on valacyclovir versus 22% of days on placebo
(p<0.001). HIV-1 plasma viral load was significantly lower during the
valacyclovir arm compared with the placebo arm (4.34 vs 4.61 log10
copies/mL, p <0.001; difference –0.27 log10 copies/mL, 95%
confidence interval –0.34 to –0.20). Cervical HIV-1 was detected at 54% of
visits while on valacyclovir versus 71% of visits while on placebo (p <0.001).
Cervical HIV-1 levels were significantly lower while on valacyclovir compared
with placebo (2.87 vs 3.23 log10 copies/swab, p <0.001;
difference –0.35 log10 copies/swab, 95% confidence interval –0.46 to
–0.25).
Conclusions: 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.
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