Hep C deaths outpace HIV; new drugs, services for coinfected
by Liz Highleyman
Deaths related to hepatitis C have outpaced those due to HIV/AIDS since 2007, researchers reported at the American Association for the Study of Liver Diseases meeting earlier this month in San Francisco.
People coinfected with both hepatitis C virus and HIV experience faster liver disease progression and do not respond as well to standard interferon treatment. The Positive Health Program at San Francisco General Hospital has pioneered a successful model of treatment for coinfected people, and two recent studies showed that new hepatitis C drugs can improve treatment outcomes for this group.
Hepatitis and HIV deaths
Researchers with the Centers for Disease Control and Prevention looked at more than 21 million death certificates recorded between 1999 and 2007 to compare rates of mortality due to HIV and hepatitis B and C. More than 1 million Americans have chronic hepatitis B and at least 4 million have hepatitis C.
Over years or decades both forms of hepatitis can progress to life-threatening liver disease including cirrhosis and liver cancer. San Francisco has one of the highest rates of liver cancer in the U.S., largely due to the high prevalence of hepatitis B among Asians. New hepatitis B infections have fallen dramatically thanks to widespread vaccination, but there is no effective vaccine for hepatitis C.
CDC's Dr. Scott Holmberg reported that the hepatitis B death rate remained roughly stable during the study period, at around 1,800 cases. Nationwide deaths due to HIV fell during that period – to about 12,700 – after the debut of effective combination antiretroviral therapy in the mid-1990s.
But deaths due to hepatitis C increased during the same period, reaching more than 15,000 in 2007. Almost 75 percent of hepatitis C deaths were among baby boomers in the 45-64 age group, many of whom were infected years ago and remain unaware of their status. Experts think more than half of people with hepatitis C have not been diagnosed.
"Without reducing allocation of resources that have diminished HIV deaths, we think a commitment to detect and treat chronic HCV will markedly improve the growing wave of disability and death from this under-appreciated viral infection," Holmberg concluded.
Coinciding with the AASLD meeting, Silicon Valley Congressman Mike Honda, Representative Bill Cassidy (R-Louisiana), and Senator John Kerry (D-Massachusetts) introduced new legislation – the Viral Hepatitis Testing Act of 2011 – to expand funding for hepatitis B and C education, prevention, testing, and treatment.
"Passing the Viral Hepatitis Testing Act of 2011 will save lives and improve health care," Honda and Kerry wrote in a recent op-ed for the congressional newspaper the Hill. "The costs of education, research, and treatment pale in comparison to the health costs that will be incurred if we do nothing."
The CDC study found that people with HIV and hepatitis had a higher rate of death than those with hepatitis alone – about twice as high for hepatitis B and four times as high for hepatitis C. Experts estimate that approximately one third of HIV-positive people in the U.S. also have hepatitis C, a rate reflected among HIV patients at SFGH.
The Positive Health Program – a partnership between SFGH, UCSF, and the San Francisco Department of Public Health – treats about 800 HIV-positive people with hepatitis B or C.
During the past decade, epidemics of presumably sexually transmitted acute hepatitis C among HIV-positive gay and bisexual men have been reported in Europe, Australia, and the U.S. While unprotected anal intercourse, fisting, and use of drugs during sex have been implicated, the exact risk factors are not fully understood. According to PHP medical director Dr. Brad Hare, the majority of HIV/HCV-coinfected people at SFGH were likely infected via sex.
PHP's coinfected patients are treated at a primary care clinic with an integrated medical team, rather than being referred to a specialty liver disease clinic. The interdisciplinary team includes physicians, nurses, social workers, pharmacists, and psychiatrists. The program features a Tuesday afternoon HIV/hepatitis coinfection clinic and a weekly hepatitis C support group.
Vertex Pharmaceuticals announced this month that it has awarded 16 grants – totaling approximately $1.5 million – to innovative hepatitis C care and support programs, including PHP and the Organization to Achieve Solutions in Substance Abuse clinic in Oakland.
New hepatitis C drugs
As previously reported, two new hepatitis C drugs were approved by the Food and Drug Administration in May. Boceprevir (Victrelis), from Merck, and telaprevir (Incivek) from Vertex, are both HCV protease inhibitors. Unlike interferon, which stimulates the body's immune response, these direct-acting antiviral agents target the viral lifecycle.
Following their approval, Hare told the Bay Area Reporter that the new drugs are "groundbreaking," and predicted that "in the next few years many more hepatitis C drugs will become available."
Boceprevir and telaprevir were initially approved for HIV-negative adults with hard-to-treat genotype 1 hepatitis C, to be used in combination with injected pegylated interferon plus ribavirin. In clinical trials, adding either drug increased the likelihood of a cure and allowed many people to be successfully treated with shorter therapy.
Boceprevir and telaprevir are not yet approved for people with HIV, but recent study findings show they will likely also benefit.
At the AASLD meeting researchers presented interim results from a study of telaprevir plus pegyalted interferon/ribavirin in 60 HIV/HCV-coinfected patients. This analysis included some people who did not yet need HIV treatment, some who were taking efavirenz/tenofovir/emtricitabine (the drugs in Atripla), and some who were taking boosted atazanavir.
Overall, 71 percent of people taking telaprevir triple therapy had undetectable HCV viral load at 24 weeks compared with 55 percent of those taking pegyalted interferon/ribavirin alone. People not on ART did slightly better than those who used efavirenz, who in turn did somewhat better than those on atazanavir.
Side effects were more common in the telaprevir group than in the standard therapy group, but coinfected people in this trial did not have worse side effects than HIV-negative people in previous studies.
Another study, reported at the Infectious Diseases Society of America meeting last month in Boston, compared boceprevir plus pegyalted interferon/ribavirin versus standard therapy in 100 HIV/HCV-coinfected patients taking boosted protease inhibitor regimens for HIV.
Mark Sulkowski from Johns Hopkins University reported that after 24 weeks, 71 percent of participants taking boceprevir triple therapy had undetectable HCV compared with 34 percent of those using pegylated interferon/ribavirin alone. Again, people taking boceprevir experienced more side effects, but these did not differ from side effects seen in HIV-negative people.
Both studies are ongoing. Treatment will continue for 48 weeks, and participants will be followed for an additional six months to see if HCV remains undetectable, which is considered a cure.
In an effort to avoid its notorious side effects, researchers are testing several interferon-free regimens. The AASLD meeting featured numerous presentations showing promising outcomes for novel direct-acting HCV drugs both in combination with interferon and in all-oral regimens. Most trials to date have looked at HIV-negative people, but companies are now starting or planning studies for HIV/HCV-coinfected people as well.