IAS: Aciclovir treatment doesn't significantly reduce HIV or HSV-2 shedding in genital secretions

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HIV-positive women who are infected with herpes simplex virus-2 (HSV-2) experience only modest decreases in their HIV viral load in their genital secretions if they take long-term anti-herpes therapy, according to the results of a randomised controlled trial presented as a poster to the 4th International AIDS Society Conference on HIV Pathogenesis and Treatment in Sydney on July 24th. Surprisingly, the study also revealed that daily anti-herpes therapy did not significantly lower genital shedding of HSV-2.

The investigators who conducted the study presented data to the conference yesterday showing that HIV-negative women who were infected with HSV-2 who took anti-herpes treatment were not protected against infection with HIV. They believe that the reason why both results had such disappointing results was the generally poor level of adherence amongst women in the study to their medication.

Three recent studies have suggested that daily treatment with oral anti-herpes therapy can reduce the genital shedding of HIV in women coinfected with HIV and HSV-2. It is hoped that anti-herpes therapy could be a useful method of HIV prevention as it is thought that HSV-2 is implicated in as many as 50% of new HIV infections.


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.

odds ratio (OR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 


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


Refers to the mouth, for example a medicine taken by mouth.

Investigators from the UK and Tanzania therefore designed a randomised controlled trial involving women with HIV and HSV-2. They wished to see if long-term treatment with daily oral anti-herpes therapy consisting of 400mg of aciclovir reduced genital shedding of HIV and HSV-2. A total of 383 women infected with both viruses were recruited to the study in the mining area of Mwanza in north-west Tanzania. Women who worked in guest-houses and bars were targeted for recruitment to the study because they often engage in opportunistic transactional sex.

All the women were aged between 16 and 35-years. At baseline, 53% had HIV detectable in their genital secretions, with 14% having HSV-2 present.

The women were equally randomised to take daily aciclovir or a placebo. They were followed-up at three-monthly intervals and cervico-vaginal lavage was obtained at six-monthly intervals to check for the presence of both HIV and HSV-2.

At six and twelve months, women taking daily aciclovir had a trend to lower genital shedding of HIV (odds ratio: 0.83, 95% CI; 0.56 – 1.26). When the investigators excluded women who had blood or semen in their lavage, the relationship between aciclovir use and lower genital shedding of HIV strengthened (odds ratio: 0.64, 95% CI; 0.39 – 1.04). However, the investigators emphasise that, even then, viral load in the genital secretions of women taking aciclovir was not significantly lower than in those randomised to take the placebo (p = 0.07).

The investigators were also surprised to note that there was no significant difference in the genital shedding of HSV-2 between the women in the treatment and control arms of the study.

Extensive efforts were made to monitor adherence. Women were counselled at follow-up visits about the importance of adherence. There were regular pill counts and two random urine tests to check aciclovir levels. This monitoring revealed that only 50% of women had 90% or better adherence to their aciclovir therapy. The investigators believe that this is the reason for the disappointing results of the study.

Dr Debby Watson-Jones, of the London School of Hygiene and Tropical Medicine commented: “One thing that this study makes clear is that maintaining adherence to aciclovir over a long period is challenging…an effective HSV-2 vaccine would obviously be a more practical way of controlling this virus, and the development of a vaccine needs to be given higher priority.”

The investigators are hopeful that more intensive support will yield more encouraging results by the time they have two years of data.


Tanton C et al. A randomized controlled trial in Tanzania to assess the impact of HSV-2 suppressive therapy on genital HIV viral load among HSV-2 and HIV-1 seropositive women. Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, abstract TUPEC011, Sydney, 2007.