By Liz Highleyman

A study conducted in Africa and published last week in the New England Journal of Medicine has shown that use of the anti-herpes drug valacyclovir (Valtrex) can reduce levels of HIV in the bloodstream and genital tract, and may be a relatively simple way to help reduce HIV transmission.

It is estimated that approximately 20% of Americans and 60% of Africans are currently infected with some form of herpes simplex virus (HSV). HSV-1 is associated with oral ulcers (cold sores) and HSV-2 usually causes genital herpes, though both viruses can infect either area. HSV-2 coinfection is believed to increase the likelihood of HIV transmission during sexual intercourse.

In addition to producing open genital ulcers that allow HIV entry into the body, HSV infection also causes activated T-cells -- primed for HIV infection -- to gather at the site of active herpes lesions. HSV coinfection is also associated with increased HIV shedding in the genital tract.

The present double-blind, controlled study was conducted in the West African nation of Burkina Faso. It included 140 women who were seropositive for both HIV and HSV-2, and who were not eligible to receive antiretroviral therapy. The women were randomly assigned to receive either 500 mg twice-daily valacyclovir or placebo for 3 months.

Results

• 140 women were randomly assigned to treatment or placebo groups; 136 were included in the analyses.

• At enrollment, the median CD4 cell count was 446 cells/mm3 and the mean plasma HIV viral load was 4.44 log10 copies/mL.

• Using summary-measures analysis, valacyclovir therapy was associated with a significant decrease in the frequency of detectable genital HIV RNA and the mean quantity of virus.

• HSV suppressive therapy also reduced the mean plasma HIV RNA level by 0.53 log10 copies/mL.

• Repeated-measures analysis showed that these effects became significantly stronger over the course of the 3-month follow-up period.

• No serious adverse events or cases of hepatic or renal impairment associated with valacyclovir were reported, and the frequency of mild-to-moderate side effects was similar in the 2 groups

Conclusion

In conclusion, the authors wrote, "In this study, daily treatment with valacyclovir for 3 months significantly diminished the shedding of HIV-1 RNA, reduced plasma HIV-1 RNA levels, and reduced genital HIV-1 RNA levels when shedding was present in women dually infected with HIV-1 and HSV-2."

They added that, "This effect steadily increased over time, which suggested that a longer duration of treatment might have led to an even greater reduction in HIV-1 RNA levels."

"This finding may have important implications for HIV control," they concluded.
The relationship between HSV and HIV replication, one of the main findings of this study, will hopefully be exploited in the future with the use of herpes treatments including valacyclovir and/or acyclovir (Zovirax and generics) -- a similar but much less expensive drug -- to help control HIV transmission.

Preliminary data from a similar study in Thailand, presented Monday, February 26, at the 14th annual Retrovirus conference in Los Angeles, suggest that acyclovir likewise reduces HIV viral load in female genital fluids, though the study had not yet been unblinded at the time the abstract was submitted.

02/27/07

References

N Nagot, A Ouédraogo, V Foulongne, and others. Reduction of HIV-1 RNA Levels with Therapy to Suppress Herpes Simplex Virus. New England Journal of Medicine 356(8): 790-799. February 22, 2007.

E Dunne, S Whitehead, M Sternberg, and others. The effect of suppressive acyclovir therapy on HIV cervicovaginal shedding in HIV and HSV-2-infected women, Chiang Rai, Thailand. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles. February 25-28, 2007. Abstract 30.