Anti-herpes therapy reduces genital and plasma HIV viral load in MSM not taking HIV therapy

This article is more than 12 years old. Click here for more recent articles on this topic

Daily treatment with the anti-herpes drug valaciclovir significantly reduced HIV viral load in both the blood and genital secretions of HIV/herpes simplex virus-2-infected men who have sex with men (MSM), according to a study conducted in Lima, Peru and published in the November 15th edition of the Journal of Infectious Diseases.

The reduction in HIV viral load in the blood achieved with anti-herpes therapy was similar to that seen with antiretroviral monotherapy, but without monotherapy’s risk of anti-HIV drug resistance.

Suppressing viral load in both genital secretions and blood with anti-herpes therapy could have clinical benefits for the individual and help prevent the onward transmission of HIV. But the investigators call for larger, longer studies to see if suppressive anti-herpes therapy could actually delay HIV disease progression and the need to start antiretroviral therapy.

Glossary

herpes simplex virus (HSV)

A viral infection which may cause sores around the mouth or genitals.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

rectum

The last part of the large intestine just above the anus.

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

monotherapy

Taking a drug on its own, rather than in combination with other drugs.

Most HIV-positive individuals are also infected with herpes simplex virus-2 (HSV-2), the virus that can cause anogenital herpes.

Genital ulcers have been associated with an increased risk of HIV acquisition in HIV-negative patients and an elevated risk of HIV transmission in HIV-positive patients.

Daily anti-herpes medication has been shown to prevent both HSV-2 shedding and symptoms. A study in Burkina Faso demonstrated that treatment with the anti-herpes drug, valaciclovir, significantly reduced both cervical and blood levels of HIV.

Furthermore, studies conducted in the 1990s showed that anti-herpes therapy in the context of single- or two-drug antiretroviral therapy was associated with a survival benefit.

Investigators therefore designed a study to determine the effects of twice-daily treatment with 500mg doses of oral valaciclovir on anogenital and blood levels of HSV-2 and HIV. The study population consisted of 20 HIV-positive MSM in Lima, Peru. None were taking antiretroviral therapy. All had a CD4 cell count above 200 cells/mm3.

The study had a double-blind, randomised, placebo-controlled, cross-over design. On entry to the study the men were randomly assigned to receive either valaciclovir or the placebo for eight weeks. This was followed by a two week ‘wash-out’ period after which the men swapped treatment arm for a further eight weeks.

On entry to the study the men were screened for sexually transmitted infections and had blood and genital samples taken. The men were required to attend the clinic three times a week to provide further samples and also took daily skin and genital swabs at home.

Median CD4 cell count was 406 cells/mm3 and median age was 31 years. A previous attack of anogenital herpes was reported by four of the men (20%).

High levels of adherence to the study protocol were recorded, with individuals attending an average of 46 of the 48 clinic appointments and pill counts showed that the men took 96% of their treatment doses.

HSV-2 detection

HSV-2 was detected in 29% of swabs obtained during placebo treatment and 4% of swabs taken during valaciclovir therapy, a statistically significant difference (p < 0.001).

HIV in rectal samples

HIV was detected in 78% rectal mucosal samples taken during placebo therapy and 69% of such samples obtained during valaciclovir treatment. Once again this difference had statistical significance (p = 0.02).

Mean HIV viral load in rectal samples during placebo treatment was 100,000 copies/ml compared to 63,000 copies/ml during anti-herpes treatment. This was statistically significant (p < 0.001).

In each individual, valaciclovir treatment was associated with a 31% drop in rectal HIV viral load compared to treatment with a placebo (p = 0.0008).

HIV in blood

HIV was found in 99% of the 288 blood samples the men provided. Mean viral load during valaciclovir treatment was approximately 14,000 copies/ml compared to a mean viral load of 32,000 copies/ml during treatment with the placebo (p < 0.001).

In each individual, treatment with valaciclovir achieved a 53% drop in viral load compared to treatment with the placebo (p < 0.0001). The investigators found that the higher a patient’s CD4 cell count during valaciclovir therapy, the greater the fall in viral load (p = 0.018).

“Our findings show that antiviral drugs that effectively suppress HSV reactivation significantly reduce plasma and mucosal HIV-1 RNA among HIV-1/HSV-2 coinfected MSM”, comment the investigators.

But the investigators caution that further studies are needed to show that valaciclovir treatment in patients with HIV and HSV-2 reduces the risk of transmission or delays HIV disease progression.

References

Zuckerman RA et al. Herpes simplex virus (HSV) suppression with valaciclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomised, double blind, placebo-controlled crossover trial. J Infect Dis 196: 1500 – 1508, 2007.