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Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus

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HIV-positive women taking valaciclovir were found to have reduced plasma HIV levels.

What’s known?

  • Herpes simplex virus type 2 (HSV-2) has been recognized as the most common cause of genital ulcers in the developed world and recent studies show that HSV-2 is a common cause of genital ulcers in the developing world
  • HIV replication is compartmentalized in anatomic sites of the body, and the interactions between HIV type 1 (HIV-1) and microbes occupying these anatomic sites influence the amount and strain of HIV-1 in these regions
  • Epidemiologic and biologic data support a strong association between herpes simplex virus type 2 (HSV-2) and infection with human immunodeficiency virus type 1 (HIV-1)
  • Symptomatic HSV-2 reactivation has been associated with transient increases in plasma HIV-1 RNA levels and acyclovir treatment with reduced plasma HIV-1 RNA levels.

What’s new?

  • The authors conducted a double-blind, placebo-controlled trial of 500 mg of valaciclvoir twice daily for 3 months among women who were dually infected with HIV-1 and HSV-2 in Bobo-Dioulasso, Burkina Faso
  • Women who were at least 16 years of age, had serum antibodies to both HSV-2 and HIV-1, and were not eligible for HAART were enrolled in the study
  • Cervicovaginal lavage enriched by cervical swabbing was performed for the detection and quantitation of genital HIV-1 RNA and HSV-2 DNA
  • HIV-1 RNA and HSV-2 DNA were quantitated by real-time polymerase-chain-reaction assay
  • 136 (68 in each group) were included in the analyses. The median CD4 cell count was 446 cells per cubic millimetre and the mean plasma HIV-1 RNA level was 4.44 log10 copies per millilitre
  • On the basis of the pill count, the average treatment compliance was 97.2% in the valaciclovir group and 96.7% in the placebo group
  • Valaciclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA (odds ratio, 0.41; 95% confidence interval [CI], 0.21 to 0.80) and in the mean quantity of the virus (log10 copies per millilitre, –0.29; 95% CI, –0.44 to –0.15)
  • The mean quantity of plasma HIV-1 RNA among women in the valaciclovir group was significantly lower than in the placebo group (–0.53 log10 copy per millilitre; 95% CI, –0.72 to –0.35, adjusted for mean baseline-phase value; P<0.001). In addition, the treatment effect on plasma HIV-1 RNA increased with time (P<0.001), with an average reduction of 0.09 log10 copy per millilitre every 2 weeks
  • The authors concluded that HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women
     
Research summary
Author(s): 

Nicolas Nagot, Abdoulaye Ouédraogo, Vincent Foulongne, Issouf Konaté, Helen A. Weiss, Laurence Vergne, Marie-Christine Defer, Didier Djagbaré, Anselme Sanon, Jean-Baptiste Andonaba, Pierre Becquart, Michel Segondy, Roselyne Vallo, Adrien Sawadogo, Philippe Van de Perre, Philippe Mayaud, for the ANRS 1285 Study Group

Full title: 

Reduction of HIV-1 RNA Levels with Therapy to Suppress Herpes Simplex Virus

Publication details: 

NEJM 2007; 356: 790-799

Abstract: 

Background: Epidemiologic data suggest that infection with herpes simplex virus type 2 (HSV-2) is associated with increased genital shedding of human immunodeficiency virus type 1 (HIV-1) RNA and HIV-1 transmissibility.

Methods: We conducted a randomized, double-blind, placebo-controlled trial of HSV suppressive therapy with valacyclovir (at a dose of 500 mg twice daily) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2; all were ineligible for highly active antiretroviral therapy. The patients were followed for 24 weeks (12 weeks before and 12 weeks after randomization). Regression models were used to assess the effect of valacyclovir on the presence and quantity of genital and plasma HIV-1 RNA and genital HSV-2 DNA during treatment, adjusting for baseline values, and to evaluate the effect over time.

Results: A total of 140 women were randomly assigned to treatment groups; 136 were included in the analyses. At enrollment, the median CD4 cell count was 446 cells per cubic millimeter, and the mean plasma viral load was 4.44 log10 copies per milliliter. With the use of summary-measures analysis, valacyclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA (odds ratio, 0.41; 95% confidence interval [CI], 0.21 to 0.80) and in the mean quantity of the virus (log10 copies per milliliter, –0.29; 95% CI, –0.44 to –0.15). However, there was no significant decrease in detection of HIV (risk ratio, 0.93; 95% CI, 0.81 to 1.07). HSV suppressive therapy also reduced the mean plasma HIV-1 RNA level by 0.53 log10 copy per milliliter (95% CI, –0.72 to –0.35). Repeated-measures analysis showed that these effects became significantly stronger during the 3 months of follow-up.

Conclusions: HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women. This finding may have important implications for HIV control.

More information
Web links: 
Full text: New England Journal of Medicine
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