The VOICE results, loud and clear: Adherence matters

The trial known as VOICE—for Vaginal and Oral Interventions to Control the Epidemic—was launched in 2009 to evaluate the efficacy of daily topical and oral antiviral drugs in preventing HIV transmission among high-risk heterosexual women from three African countries. 

But the latest round of disappointing findings from the large-scale study of 5,029 women from 15 sites in Uganda, South Africa and Zimbabwe suggest more long-acting products may be needed if this biomedical tool, known as pre-exposure prophylaxis (PrEP), is to work. 

Jeanne Marrazzo, a researcher from the University of Washington, which led the VOICE trial, reported that adherence to PrEP was low based on biological tests, and that none of the daily topical or oral regimens evaluated in the trial could be linked to a decline in HIV acquisition. This, she said, was probably due to low adherence. 

Marrazzo, who presented the data at the 20th Conference on Retroviruses and Opportunistic Infections, pointed out that the highest rates of new HIV infections were seen among women under age 25. She said subsequent analyses will try to get at the root of why women failed to stick to PrEP. “Obviously we were disappointed,” she said. 

Yet the data presented by Marrazzo was not entirely surprising. In the fall of 2011, one arm of the trial was stopped for futility after a data safety monitoring committee determined that it would be impossible to show any difference between oral TDF and placebo in preventing HIV infection (see VAX Sep. 2011 Vaccine Briefs). Two months later, the data safety monitoring committee reached the same conclusion on the topical administration of 1% tenofovir gel, a microbicide. The remaining arm of the trial tested daily administration of Truvada—a combination of TDF and emtricitabine. 

The data from that segment were sobering. The trial found an HIV incidence of 5.7% across all groups, which climbed to as much as 8.8% among unmarried women from South Africa who are under the age of 25. “The rate of acquisition did not differ product to product,” noted Marrazzo. “Adherence was low across the bar.” 

The poor adherence mirrored findings from another trial, FEM-PrEP, which was also stopped early for futility (seeVaccine Briefs, IAVI Report, Mar.-Apr 2011). The trial was conducted in Africa and led by Family Health International (FHI) 360 in North Carolina. Tim Mastro, who oversees research and programs in global health, population and nutrition at FHI 360, remarked that the PrEP findings are “sobering” and reflect a “tremendous disconnect between perception and willingness to take product.” 

Study investigators were unable to say why the women who enrolled in VOICE didn’t stick to their assigned regimens, but they hope a sub-analysis now underway will be able to shed some light on some of these behavioral questions. 

In a related PrEP talk, Chasity Andrews, a scientist at the Aaron Diamond AIDS Research Center in New York, reported results of a study of 16 Indian rhesus macaques that suggests an alternative to daily PrEP.

The study evaluated the ability of GSK744, a long-lasting second generation drug, to protect monkeys from simian-human immunodeficiency (SHIV). GSK744 belongs to a family of drugs called strand transfer inhibitors, which block integrase, the protein HIV uses to insert its genetic material into cellular chromosomes. 

Clinical studies have suggested that a single intramuscular injection of GSK744 can be detected for up to 48 weeks, which makes it an attractive option for both HIV treatment and PrEP. Andrews said eight monkeys who were injected intramuscularly with a long-acting form of GSK744 twice over a four week period were protected against repeat intrarectal SHIV challenge. All eight control monkeys became infected after a median of two rectal challenges. 

Andrews said the results suggest that GSK744, when injected quarterly or monthly, might be an effective alternative to daily oral PrEP or topical PrEP.