Aciclovir does not reduce risk of HIV transmission in serodiscordant couples

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Daily aciclovir treatment does not reduce the risk of HIV transmission when taken by individuals co-infected with HIV and herpes simplex virus-2 (HSV-2), the results of the Partners in Prevention HSV/HIV Transmission Study shows. Details were released today by the University of Washington, Seattle, which co-ordinated the study.

The research involved just over 3400 serodiscordant heterosexual couples in seven African countries where one partner was co-infected with HIV and HSV-2, and the other was HIV-negative. The HIV-positive partners were randomly assigned to take twice-daily aciclovir as suppressive treatment for herpes or a placebo.

All the HIV-positive individuals had a CD4 cell count above 350 cells/mm3 and none were taking antiretroviral treatment. The study was conducted between 2004 and 2008. The study participants were provided with intensive safer sex counselling, condoms and treatment for sexually transmitted infections. Care was provided for HIV-positive individuals, and antiretroviral therapy was initiated once a patient’s CD4 cell count dropped below 200 cells/mm3.

Glossary

herpes simplex virus (HSV)

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

disease progression

The worsening of a disease.

placebo

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

serodiscordant

A serodiscordant couple is one in which one partner has HIV and the other has not. Many people dislike this word as it implies disagreement or conflict. Alternative terms include mixed status, magnetic or serodifferent.

malaria

A serious disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. 

The study failed to show that daily aciclovir reduced the risk of HIV transmission. There were 41 new HIV infections in the aciclovir arm, compared to 43 new HIV infections in the placebo arm, a non-significant difference.

Aciclovir treatment did, however, lead to a 73% reduction in the frequency of genital ulcerative disease. It was also associated with a 0.25 log10 fall (approximately 40%) in HIV viral load.

This reduction in viral load was associated with a modest reduction in the risk of HIV disease progression. Individuals taking aciclovir were 17% less likely to experience HIV disease progression - a drop in their CD4 cell count below 200 cells/mm3.

Despite being disappointed by the study’s main finding, the investigators stressed that it had provided important information that will benefit researchers in the future.

“We have demonstrated that interventions must achieve a bigger reduction in HIV levels in order to reduce HIV transmission”, said lead investigator Dr Connie Celum of the University of Washington, Seattle.

“The findings will bear fruit for both the HIV prevention and vaccine fields for years to come…we now better understand the relationship between HIV levels and HIV transmission. This shows that the ‘bar’ is higher than we anticipated for the amount of reduction in HIV levels needed in order to reduce HIV infectiousness and transmission. This is relevant for other interventions,” Celum said, “such as antiretroviral drugs to treat HIV, treatment of co-infections such as malaria, and therapeutic HIV vaccines. This understanding is a major contribution to HIV research that will help guide our search for new HIV prevention and treatment strategies.”

Detailed results of the research, which was conducted by the University of Washington, Seattle and supported by the Bill and Melinda Gates Foundation, will be presented to the International AIDS Society conference in Cape Town in July.