ROME – Game-changing evidence that antiretroviral agents can be used by HIV-infected and uninfected populations to prevent transmission is pushing the issue of how much broader use of antiretrovirals will fit into clinical practice.
"In the United States, only 19% of those who are HIV positive have an undetectable viral load," said Dr. Julio Montaner, director of the British Columbia Center for Excellence in HIV/AIDS (Clin. Infect. Dis. 2011;52:793-800). That means that a majority of people currently eligible for antiretroviral therapy are not receiving enough of it, even in developed-world settings, he said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.
In sub-Saharan Africa, a maximum of 35% of people who are eligible for antiretroviral therapy (ART) under conservative eligibility guidelines are receiving it now, said Dr. Wafaa El-Sadr, of Columbia University in New York. Evidence from randomized controlled trials shows that early treatment prevents transmission in serodiscordant heterosexual couples, a majority of them married. However, serodiscordant married couples might not be the ideal – or only – targets for expanded ART. "ART is not a simple intervention," she said, adding, "retention in ART is suboptimal."
Issues of broader testing, therapy adherence, possible resistance, and the cost of such prophylactic interventions all remain to be worked out.
It’s not clear if and how oral antiretrovirals currently in use will be licensed for pre-exposure prophylaxis (PrEP) and Treatment as Prevention (TasP), said Tim Farley, Ph.D., head of microbicide research at the World Health Organization. Whether broad or narrow extensions of indications for tenofovir and tenofovir/emtricitabine will be sought remains to be addressed.
The broadest indication would allow these medications to be prescribed to anyone deemed at risk of contracting HIV; narrower indications might limit them to members of groups shown to benefit in randomized controlled trials, such the HIV-negative member of a serodiscordant couple. Licensing that targets specific groups, such as men who have sex with men, could be problematic in many countries, he said.
Off-label use of oral antiretrovirals was an immediate possibility in developing countries, said Dr. Farley, who added that WHO was considering issuing guidelines that would promote their use in prevention as an interim measure in advance of extended indications.
The U.S. Food and Drug Administration was meeting with drug manufacturers in an effort to get started on an extension of agents’ indications, Dr. Farley said, and the European Medicines Agency has said that it might make use of its legal ability to endorse indications for use outside the European community in order to promote the adoption of the antiretrovirals as a preventive strategy in African countries.
The issue of fast, broad access was of critical concern given that another proven HIV prevention intervention – tenofovir gel – languishes in regulatory limbo. At the conference, women advocates marched through the site with signs shouting: "Where the hell is our gel?"
The presenters did not disclose whether or not they had conflicts of interest.