Treating Hepatitis C in People With HIV

Hepatitis C is an infectious disease affecting the liver, which is transmitted by the hepatitis C virus (HCV) and is one of the leading causes of hospitalization and death among people with HIV.

The American Association for the Study of Liver Diseases (AASLD) reports that viral hepatitis—which include hepatitis A, B, and C—is today the leading cause of death worldwide, with the loss of life exceeding that of AIDS, tuberculosis, and malaria.

There is currently no vaccine for hepatitis C.

HIV/HCV Coinfection

The reported prevalence of HIV/HCV coinfection tends to vary by study, but research strongly suggests that the rate of HCV infection among people with HIV is as high as 30 percent in the U.S. and Europe. Globally, the overall HIV/HCV burden is around 4-5 million people, or between 10-15 percent of the HIV population.

Injection drug users (IDUs) have the highest risk for HIV/HCV coinfection, with prevalence ranging from 82 percent to 93 percent. By contrast, coinfection by way of sexual transmission is around 9 percent.

While men who have sex with men (MSM) don’t inherently have an increased risk for HCV infection, the risk can increase to as high as 23 percent in MSM with high-risk behaviors—such as multiple sexual partners, group sex, or even shared drugs taken nasally or anally.

Coinfected people generally have higher HCV viral loads than their monoinfected counterparts, resulting in an accelerated progression to fibrosis, cirrhosis, and hepatocellular carcinoma (the most common type of liver cancer).

Moreover, coinfected people have a threefold greater risk of antiretroviral-associated hepatotoxicity (liver toxicity) than those with HIV alone.

These figures demonstrate the need for greater identification of HCV among people with HIV, as well as more effective treatments to either clear HCV infection or, at the very least, slow disease progression.

When to Start Treatment

When to start HCV can be a complicated issue. Generally speaking, HCV treatment is indicated in individuals with proven HCV-associated liver abnormalities. The U.S. Department of Health and Human Services  (DHHS) currently recommends that HCV treatment be started in coinfected individuals who have significant fibrosis and are at higher risk for the development of cirrhosis.

Because of the significant potential for drug side effects—alongside the fact that treatment does not entirely guarantee HCV clearance—the decision to treat is based largely on patient readiness, as well as assessment the prognostic indicators for treatment success (e.g., HCV genotype, HCV viral load).

However, it's important to note that ever-improving HCV drugs are fast reducing barriers to treatment, with the benefits of therapy far outweighing the potential consequences.

The DHHS further recommends the use of combination antiretroviral therapy (ART) in all coinfected people regardless of CD4 count, which has been shown to slow the progression of HCV-associated disease. Furthermore:

• For persons with low CD4 counts (under 200 cells/mL), HCV treatment should be delayed until such time as the CD4 increases. The selection of antiretroviral medication is wholly contingent upon potential drug-drug interactions, as well as overlapping toxicities. (The main concern is that some of the drugs used in HCV treatment are metabolized in the same pathways as some antiretrovirals, reducing drug efficacy of both while increasing side effect risk.)

• For individual already on ART, consideration should be made to revise treatment to minimize likely side effects, with the benefits of changing again outweighing concerns about the potential development of HIV drug resistance.
• For untreated individuals with CD4 counts over 500 cells/mL, clinicians may choose to delay ART until completion of HCV treatment.

Overview of HCV Medication Options

The backbone of HCV treatment has long been the combination of pegylated interferon alpha (or PEG-IFN) and ribavirin. PEG-IFN is a combination of three antivirals that elicits cells to produce a large amount of enzymes able to kill both the virus and infected host cells.

Ribavirin, another antiviral agent, interferes with RNA metabolism necessary for viral replication.

Newer direct acting antivirals (DAAs) are increasingly able to treat a variety of hepatitis C genotypes without the use of PEG-INF and, in many cases, ribavirin. By doing so, the side effects associated with HCV therapy is greatly reduced, as is the duration of treament.

Among the currently approved DAAs used in the treatment of chronic hepatitis C infection (by order of FDA approval):

Common Side Effects

One of the main concerns about treating HIV/HCV coinfection is the potential side effects than may occur as a result of therapy.  While the introduction of newer generation drugs has transformed the treatment of HCV infection, there’s no underplaying the challenges that some patients face.

For persons starting therapy for the first time, the most commonly side effects of HCV therapy (occurring in at least 5% of cases) are:

• Epclusa: fatigue, headache
• Zepatier: fatigue, headache, nausea
• Daklinza: fatigue, headache, nausea, diarrhea
• Technivie: physical weakness, fatigue, nausea, insomnia
• Viekira Pak: fatigue, nausea, itchy skin,skin reaction, insomnia, weakness, fatigue
• Harvoni: fatigue, headache
• Sovaldi + PEG/INF + ribavirin: fatigue, insomnia, nausea, headache, anemia
• Sovaldi + ribavirin: fatigue, headache
• Olysio + PEG/INF + ribavirin: rash, itchy skin, nausea, muscle pain, shortness of breath

While many of the side effects are transient, resolving within a week or two of initiation, some symptoms may be prolonged and pronounced (particularly in PEG/INF-based therapies). Speak with your doctor immediately if symptoms are concerning and/or persistent. 

Before Starting HCV Therapy

Understanding and anticipating possible side effects are key to individualizing therapy and achieving optimal treatment goals. Pill burden, dosing schedules, and dietary changes (i.e., increasing fat intake for those on low-fat diets) are just some of the issues that need to be addressed to better ensure patient preparedness.

And while drug selection may be considered key to treatment success, so, too, is drug adherence. It relates not only to better outcomes but in many instances reduces the incidence and severity of side effects. Suboptimal adherence is, in fact, as much a factor to the likelihood of treatment failure as are adverse treatment events.

Liver Transplants

Cirrhosis due to chronic HCV infection is a leading indicator for liver transplants in the U.S. , Europe, and Japan, though the virus is known to recur in about 70 percent of transplant recipients within three years. Additionally, infection of the graft itself can result in between 10-30 percent of patients developing cirrhosis within a period of five years.

In individuals requiring a liver transplant, initiation of HCV triple therapy can significantly reduce the risk of graft loss by about 30%.

Despite the associative risks, it’s important to note that patient survival rate is comparable to all other indications for liver transplants—with post-operative survival rates of between 68% and 84% within the first five years.

Newer generation HCV medications may likely advance these results, while allaying the high level of drug side effects associated with treatment.

Sources:

American Association for the Study of Liver Disease (AASLD). "Assessing the Global and Regional Burden of Liver Disease." Washington, D.C. Press release issued November 3, 2013.

Rotman, Y. and Liang, T. "Coinfection with Hepatitis C Virus and Human Immunodeficiency Virus: Virological, Immunological, and Clinical Outcomes." Journal of Virology. August 2009; 83(15): 7366-7374.

Danta, M.; Brown, D.; Bhagani, S.; et al. "Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours." AIDS. May 11, 2007; 21(8):983-991.

Sulkowski, M. and Benhamou, Y. "Therapeutic issues in HIV/HCV-coinfected patients."  Journal of Viral Hepatitis. June 1, 2007; 14(6):371-388.

Ghany, M.; Strader, D.; Thomas, D; and Seeff, L.  "Diagnosis, Management, and Treatment of Hepatitis C: An Update." Hepatology. 2009; 49(4):1335-1374.

U.S. Department of Health and Human Services. "Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents." Washington, D.C.; March 27, 2012.

Alcorn, K. “Triple-drug HCV therapy comes with high risk of serious adverse events for people with cirrhosis.” NAM/AIDSMAP. April 30, 2013.

U.S. Food and Drug Administration (FDA). "FDA approves Technivie for treatment of chronic hepatitis C genotype 4."  Silver Spring, Maryland; press release issued July 24, 2015.

U.S. Food and Drug Administration (FDA). "FDA approves Viekira Pak to treat hepatitis C." Silver Spring, Maryland; press release issued December 19, 2014.

U.S. Food and Drug Administration (FDA). "FDA approves new treatment for hepatitis C virus." Silver Springs, Maryland; press release issued November 22, 2013.

U.S. Food and Drug Administration (FDA). "FDA approves first combination drug to treat hepatitis C." Silver Spring, Maryland; press release issued October 10, 2014.

U.S. Food and Drug Administration (FDA). "Olysio (simeprevir) for the treatment of chronic HCV in combination antiviral therapy." Silver Springs, Maryland. Press release issued November 22, 2013.

Manns, M. and Cornberg, M. "Sofosbuvir: the final nail in the coffin for hepatitis C?" Lancet. March 15, 2013; 13(5):378-379.

Tsoulfas, G.; Goulis, I; Papanikolaou, V.; et al. "HIV and Liver Transplantation." Hippokratia. October-December 2009; 13(4):211-215.

Sulkowski, M.; Naggie, S.; Lalezari, J.; et al. "Sovaldi and Ribivirin for Hepatitis C in Patients with Hepatitis C Coinfection."