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Drug therapy to prevent HIV infection also appeared to reduce the risk of catching another virus, herpes simplex 2 (HSV-2), among heterosexual men and women, researchers reported.

In a large randomized trial, taking daily medication including tenofovir (Viread) was found to cut the risk of acquiring HIV by up to 75%, according to , of the University of Washington in Seattle, and colleagues.

But a subgroup analysis showed that the medication also prevented acquisition of HSV-2, Celum and colleagues reported in the July 1 issue of

It's an extra benefit for HIV pre-exposure prophylaxis (PrEP) in serodiscordant heterosexual couples -- those in which one partner has HIV and the other does not.

HSV-2 is known to elevate the risk of HIV infection; studies suggest a threefold increased risk for HIV acquisition due to prevalent HSV-2 infection and up to a six-fold increase with incident HSV-2 infection, the researchers noted.

The virus is also widespread around the world and especially in Africa, where the Partners PrEP trial was conducted among 4,747 heterosexual couples enrolled from July 2008 through November 2010.

But the study originally did not include an analysis of HSV-2 acquisition as part of its protocol, Celum and colleagues noted, until in 2010 a randomized trial showed that pericoital dosing with a 1% tenofovir gel showed efficacy against the virus.

While the effect was not anticipated, they added, it was possible to assess it among the 1,498 participants who were both free of HSV-2 at baseline and had a final study visit sample available for testing.

The main study randomly assigned the HIV seronegative participants to take daily tenofovir, tenofovir/emtricitabine (Truvada), or placebo for up to 36 months of follow-up.

The placebo group in the trial was stopped early, after the data safety and monitoring board said there was clear evidence that the PrEP was effective.

HSV-2 outcomes remained blinded until all the testing and determination of endpoints was concluded; to correspond with the primary HIV results, the researchers included data through July 2011 in the HSV-2 analysis.

Tenofovir has in vitro activity against HSV-2, while emtricitabine is not known to have such an effect. For that reason, the researchers combined the two active treatment arms and compared HSV-2 outcomes with the placebo arm.

All told, they found that 131 participants had an incident HSV-2 infection, including 79 in the tenofovir groups and 52 in the placebo group, yielding incidence rates of 5.6 and 7.7 cases per 100 person-years, respectively.

The hazard ratio for HSV-2 was 0.70 for PrEP compared with placebo (95% CI 0.49-0.99, P=0.047).

Among the 1,044 couples where the HIV-positive partner was also HSV-2-positive, the incidence of HSV-2 in the uninfected partners was 10.1 and 7.0 per 100 person-years in the placebo and PrEP groups, respectively.

The HR in that subset with documented exposure to HSV-2 was 0.67 (95% CI 0.46-0.98, P=0.038).

The researchers noted that adherence to the daily therapy was high -- 98% of the dispensed pill bottles were returned and pill counts suggested that 96% of medication was taken.

The protective effect -- 33% in those with documented exposures to HSV-2 -- is the "first evidence of efficacy" of tenofovir-based PrEP against HSV-2 in a heterosexual population with high adherence, Celum and colleagues argued.

The finding is consistent with the 51% protection seen in the 2010 trial of tenofovir gel and is biologically plausible, given the evidence that the drug inhibits HSV-2 in lab studies, they argued.

The researchers noted they were unable to detect and exclude people with acute HSV-2 infection at baseline, because there is no method to do so. One in 10 of the incident infections occurred in partnerships where the HIV-1–positive partner was HSV-2–seronegative at baseline, but it was also not possible to analyze HSV-2 strains in order to investigate the origin of the infections.

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