CROI: Aciclovir treatment for genital herpes does not reduce HIV acquisition in men or women, major trial shows

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Another study has confirmed that twice daily aciclovir treatment to suppress HSV-2 (the virus that causes genital herpes), does not reduce the risk of HIV infection. The findings, from the HIV Prevention Trials Network study 039 were presented on Monday at the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston.

Lead investigator Connie Celum of the University of Washington, Seattle, described the findings as “a surprising, disappointing and important result for HIV prevention.”

Multiple epidemiologic studies have reported a 2- to 3-fold higher susceptibility to HIV among people infected with HSV-2, the most common cause of genital herpes. HPTN 039 was designed to test the hypothesis that suppressing HSV-2 with oral aciclovir would reduce the sexual transmission of HIV among this group.

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.

retention in care

A patient’s regular and ongoing engagement with medical care at a health care facility. 

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

hypothesis

A tentative explanation for an observation, phenomenon, or scientific problem. The purpose of a research study is to test whether the hypothesis is true or not.

Another study, looking at aciclovir suppressive treatment in women in Tanzania, reported last year that aciclovir was not effective in reducing the risk of HIV acquisition.

The randomised, placebo-controlled trial enrolled 3251 HSV-2-positive, HIV-negative participants: 1871 men who have sex with men from the US and Peru and 1380 heterosexual women from Zimbabwe, Zambia and South Africa. All participants reported high-risk sex practices.

Participants were randomised to receive either 400 mg aciclovir twice daily or placebo. They were then followed for 12 to 18 months. Monthly visits monitored for adherence to the drug regimen and provided risk reduction counselling. HIV tests were performed quarterly.

At study entry, 12% of men and 26% of women had clinically identified genital herpes within the preceding three months. The median number of sexual partners in the 12 months leading up to the study was 10 among men and 1 among women. However, women reported a much higher frequency of sexual acts in the previous three months: 24, compared with sex for MSM. Three out of every five participants reported not knowing the HIV status of at least one of their partners.

There were 75 new HIV infections within the aciclovir group (incidence of 3.9/100 person-years) and 64 new infections within the placebo group (incidence of 3.3/100 person-years), leading to a hazard ratio (HR) of 1.16 (95%CI 0.83 to 1.62) for the aciclovir group.

There were no significant differences between the groups based on gender (HR = 0.9 for men and HR = 1.5 for women), adherence (HR = 1.6 for

However, the researchers did note that the number of genital ulcers reported by participants or during exams was reduced by 35% in the aciclovir arm compared with the placebo arm. However there was considerable regional variation in the reduction in genital ulcer disease, with a significantly greater reduction among MSM in the United States compared to women in South Africa (p

Adherence to the drug regimen by self-report and pill count was 94.3%. There were no serious adverse events due to the study drug, and retention in the trial was 88% at 18 months.

The researchers concluded that despite the excellent retention and the high adherence to the drug regimen, twice-daily aciclovir did not reduce the transmission of HIV among HSV-2-positive individuals.

Why did aciclovir suppressive treatment fail once again to reduce HIV incidence in a large trial, despite the compelling epidemiological evidence for HSV-2’s role as a co-factor in HIV transmission?

Connie Celum suggested that acyclovir levels may have been lower in African women due to poor absorption or nutritional status, but stressed that this hypothesis needed to be investigated further. She said that the findings from HPTN 039 didn’t mean the end of the line for studies looking at whether HSV-2 suppression reduced HIV transmission. Higher doses of acyclovir, new drugs or combinations of drugs and anti-HSV-2 vaccines would all need to be explored, she said.

Reference

Celum C et al. HSV-2 suppressive therapy for prevention of HIV acquisition: results of HPTN 039. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 32LB, 2008.

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