Drug prevents spread of genital herpes in HIV-negative heterosexuals: Lessons for HIV prevention

This article is more than 22 years old.

Daily treatment with valaciclovir, a drug which reduces both the shedding of herpes simplex virus-2 (HSV-2) and the appearance of genital herpes sores, is effective in reducing the transmission of HSV-2 to uninfected partners via heterosexual sex. This finding was a key presentation at the 42nd ICAAC in San Diego, and is understood to be the first randomised controlled trial evidence to indicate that antiviral drug therapy can be used to successfully reduce onward spread of a sexually transmitted infection. It is expected to be viewed with great interest by those engaged in HIV prevention, both because HSV-2 infection is known to facilitate transmission of HIV, and because ‘pre-exposure prophylactic antiretroviral therapy’ is under investigation as a potential HIV prevention tool.

The current study recruited almost 1,500 monogamous heterosexual couples in which one partner was HSV-2 seropositive and the other uninfected. The source partners were randomised to receive either valaciclovir (500mg once daily) or a matching placebo. Couples were counselled about safer sexual practices and offered condoms to prevent HSV-2 transmission at monthly clinic visits. Source partners underwent pill counts at these visits to monitor their adherence to their assigned treatment, and kept diaries of their sexual activity. Seronegative susceptible partners were monitored monthly for acquisition of HSV-2.

Overall, valaciclovir reduced the risk of symptomatic genital herpes (a visible outbreak) in the susceptible partners by 77%. The risk of acquiring HSV-2 (as determined by a positive blood test and/or lab confirmation) was reduced by 50%. Placebo recipients were observed to experience more HSV-2 shedding days and higher titres of HSV-2, known to facilitate HSV-2 transmission. Valaciclovir appeared to be well-tolerated, with a similar frequency of side-effects being reported in each group.


herpes simplex virus (HSV)

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


Viral shedding refers to the expulsion and release of virus progeny (offspring such as competent particles, virions, etc.) following replication. In HIV this process occurs in the semen, the vaginal secretions and other bodily fluids, making those fluids more infectious.


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

safer sex

Sex in which the risk of HIV and STI transmission is reduced or is minimal. Describing this as ‘safer’ rather than ‘safe’ sex reflects the fact that some safer sex practices do not completely eliminate transmission risks. In the past, ‘safer sex’ primarily referred to the use of condoms during penetrative sex, as well as being sexual in non-penetrative ways. Modern definitions should also include the use of PrEP and the HIV-positive partner having an undetectable viral load. However, some people do continue to use the term as a synonym for condom use.


In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

Despite safer sex counselling at each clinic visit, 56% of couples reported never using condoms, and 14% reported that they used condoms during sex anywhere up to 90% of the time. The remaining 30% reported that they always used condoms. Compliance to assigned treatment was relatively high at around 73% overall, though this was reported to be higher amongst valaciclovir recipients. Those who acquired HSV-2 despite their partner taking valaciclovir are now being investigated to determine whether their HSV-2 is drug resistant, a potential risk of using antimicrobial therapies in this way.

It’s important to stress that these findings cannot be generalised beyond the study population – there is no evidence that valaciclovir can reduce HSV-2 transmission between heterosexuals with multiple partners, or between men who have sex with men, or between people with HIV infection, or where couples are not counselled about safer sexual practices. Clearly, however, these are important settings for further study.

A newly described link between HSV-2 and HIV acquisition in gay men is reported here on aidsmap.com. For more information on the possible use of antiretroviral therapy in preventing the spread of HIV, click here.


Corey L et al. Once daily valaciclovir reduces transmission of genital herpes. 42nd ICAAC, San Diego, September 27-30, 2002, abstract L-773.