Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) may be out of the public eye, but curing these unseen epidemics requires ongoing research, says an expert who spoke at the 2010 annual meeting of the Society for Investigative Dermatology.
Although more than two dozen HIV drugs can alleviate suffering and prolong life, "The epidemic is not over," says Raymond Schinazi, Ph.D., D.Sc., professor of pediatrics, Emory University School of Medicine and Atlanta VA Medical Center. "We also know that more than 1 million people have been infected with HIV in the United States," and an estimated 60 million will be infected worldwide by 2015, he says, adding that only 28 percent of those who need treatment actually get it.
Before the advent of modern treatments in 1985, HIV had a 73 percent mortality rate, Dr. Schinazi says. But by 2008, more than 94 percent of people infected with HIV who receive Western standard-of-care treatment survive at least five years.
For hepatitis C virus (HCV), "We only have two drugs - ribavirin and interferon (IFN). Both are relatively toxic," Dr. Schinazi says. About 280 million people worldwide are infected with HCV. "There are 3 to 4 million infections per year globally, and we expect more than 800,000 U.S. patients to develop HCV-related cirrhosis this decade," he says.
Up to one-third of those with HCV are coinfected with HIV, Dr. Schinazi says, adding that coinfection complicates treatment because physicians must consider dangerous drug interactions. Both viruses share routes of transmission, which are all very dynamic.
"The number of patients with HCV treated in the United States is very small compared to the number of chronic carriers," Dr. Schinazi says. Treatment failures are common, he says, because the current standard of care does not work well against certain HCV genotypes. Only 30 to 60 percent of patients achieve sustained virological response (SVR, or a cure) on currently available HCV therapies, all of which require intravenous administration, he says.
More than a dozen drug candidates are under development for HCV (Sarrazin C, Zeuzem S. Gastroenterology. 2010 Feb;138(2):447-462. Epub 2009 Dec 16. Review), Dr. Schinazi says. These include small molecules and interferon-related therapies.
"There are various classes of compounds, including nucleoside and non-nucleoside polymerase inhibitors, cyclophilin inhibitors, protease inhibitors (PIs) and, more recently, the very potent NS5A inhibitors," he says.
However, Dr. Schinazi says, only two candidates are in Food and Drug Administration phase 3 trials: telaprevir (Vertex) and boceprevir (Merck/Schering-Plough). "These PIs are having a remarkable effect on viral load in persons infected with HCV," he says. NS5A inhibitors also show promise in reducing viral load, though they're only in phase 1/2.
HCV drug candidates often fail, Dr. Schinazi says, due to side effects such as anemia, gastrointestinal issues, body composition changes or dermatologic side effects. Telaprevir can cause severe rashes, he notes, a fact which "probably should have been picked up in earlier development. Unfortunately, it wasn't," which has required investigators to cut the treatment duration from six or 12 months to 12 weeks.