According to national estimates, about 15% to 30% of people with HIV in the United States are coinfected with hepatitis C virus (HCV). Reports also show that as many as 90% of those with HIV secondary to injection drug use are coinfected with HCV. The rate of progression to cirrhosis for people coinfected with HCV/HIV is about three times higher than the rate for people who only have HCV infection. This accelerated rate is magnified in patients with low CD4 counts. “HCV/HIV coinfection can result in chronic liver diseases, most notably cirrhosis but also liver cancer,” explains David L. Thomas, MD, MPH. “The coinfection can lead to significant morbidity and mortality.” Compounding the problem is that chronic HCV infection can complicate HIV treatment because it increases the frequency of antiretroviral therapy (ART)-associated hepatotoxicity.
“The accelerated rate of liver disease progression associated with HCV/HIV coinfection is an important factor to consider.”
Several clinical investigations have shown that the prognosis is poorer for HCV/HIV coinfected persons than for persons with just HIV in the era of combination ART. It is unknown if ART reduces morbidity and mortality from untreated HCV. What is known is that ART does not reduce liver mortality enough. In some centers, liver failure is one of the leading causes of death in HIV-infected persons. As a result, treatments for HCV/HIV coinfection must be individualized based on several important patient factors (Table 1).
Managing Coinfection & Using ART
Guidelines from the U.S. Department of Health and Human Services (HHS) indicate that HIV-infected patients should be screened for HCV infection with immunoassays prior to initiation of ART. Patients with HCV/HIV coinfection should also be advised to avoid drinking alcohol, use precautions to prevent transmission of both HCV and HIV to others, and receive hepatitis A and B vaccines, if susceptible. Repeat testing for HCV is also important, especially in people with unexplained elevations in liver enzymes, as new outbreaks have been reported in recent literature, according to Dr. Thomas.
According to the HHS guidelines, all patients with HCV/HIV coinfection should be evaluated for HCV therapy. HCV treatment is recommended for patients with higher CD4 counts. For patients with lower CD4 counts (<200 cells/mm3), it may be preferable to initiate ART and delay HCV therapy until CD4 counts increase.
Simultaneous treatment of HIV and HCV is feasible for many patients but may be complicated by pill burden, drug toxicities, and drug interactions. Clinicians are recommended to adhere to the current HHS guidelines when selecting specific medications for coinfected patients (Table 2). ART should be started in accordance with HHS recommendations for initiating the therapies in treatment-naïve patients. The guidelines also provide information on what to start and what not to use, based on best available evidence. “The accelerated rate of liver disease progression associated with HCV/HIV coinfection is an important factor to consider,” notes Dr. Thomas. ART may slow the progression of liver disease. For most coinfected patients, the potential benefits of ART outweigh concerns.
Once treatment with ART is initiated, clinicians should monitor patients for hepatotoxicity. Guidelines recommend that patients be monitored by following alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at 1 month and then every 3 months after initiation of ART. Mild-to-moderate fluctuations in ALT and/or AST are typical in people with chronic HCV infection. In the absence of signs or symptoms of liver disease, these fluctuations do not require ART to be interrupted. However, significant ALT and/or AST elevations should prompt careful evaluation for signs and symptoms of liver insufficiency and for alternative causes of liver injury. In these cases, short-term interruption of ART may be necessary.
Preliminary HCV/HIV Coinfection Recommendations
In May 2011, two HCV protease inhibitors (PIs) were approved by the FDA to treat people with genotype 1 chronic HCV infection, but not those coinfected with HIV. Critical safety and efficacy data are lacking, but the availability of these drugs and substantial medical need may justify off-label use of them in select HCV/HIVcoinfected patients. In the December 14, 2011 online edition of Clinical Infectious Diseases, Dr. Thomas and colleagues presented provisional guidance on the use of HCV PIs in HIV-infected patients. The preliminary recommendations stress that decisions to use HCV PIs be made on a patient-by-patient basis.
Clinical trials of HCV PIs in HCV/HIV coinfection are ongoing, but preliminary data suggest that these drugs may improve outcomes for some coinfected individuals. “More data are needed in this specific population with regard to safety, tolerability, efficacy, and interactions with available ART,” says Dr. Thomas. “In addition, other newer, easier-to-take medications are being tested and assessed to treat coinfected patients. There is hope that these emerging therapies will further enhance our treatment armamentarium. Ideally, more HCV/HIV-coinfected people will be included at earlier stages of drug development so that practical guidance can be based more on data.”
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. January 10, 2011;1-166. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Thomas DL, Bartlett JG, Peters MG, Sherman KE, Sulkowski MS, Pham PA. Provisional guidance on the use of hepatitis C virus protease inhibitors for treatment of hepatitis C in HIV-infected persons. Clin Infect Dis. 2011 Dec 14 [Epub ahead of print]. Abstract available at:http://cid.oxfordjournals.org/content/early/2011/12/14/cid.cir882.extract.
Medical Care Criteria Committee. Hepatitis C. New York State Department of Health AIDS Institute. Available at: http://www.hivguidelines.org/clinical-guidelines.
Centers for Disease Control and Prevention. HIV and Viral Hepatitis. Fact Sheet. Available at:http://www.cdc.gov/hiv/resources/factsheets/hepatitis.htm.