Evaluation and Treatment of Hepatitis C in Patients With Coexisting HIV Infection

Scott D. Parker, MD

In This Article

Expected Response Rates and Goals of HCV Therapy

The ultimate goal of HCV therapy is the prevention of advanced liver disease: cirrhosis, hepatic failure, and hepatocellular carcinoma. The progression to advanced HCV-related liver disease occurs more quickly, with an unpredictable course and with increased frequency in the HIV-infected patient population. The response to therapy in the coinfected population has been documented in 3 randomized clinical trials of patients with median CD4+ T-cell counts ranging from 450 to 550 cells/mm3: APRICOT (AIDS Pegasys Ribavirin International Coinfection Trial), ACTG 5071 (Adult AIDS Clinical Trials Group protocol A5071), and Ribavic.[4,5,6] Each study evaluated the safety and efficacy of pegylated interferon alfa vs nonpegylated interferon alfa in the coinfected patient population. Intolerance to HCV therapy was observed at a frequency similar to that seen in patients who were not infected with HIV, and rates of patient withdrawal from treatment varied from 12% to 39%. Reasons for withdrawal included clinical adverse events, lab abnormalities, and subjects' choice to discontinue therapy and follow-up. However, hepatic decompensation and related deaths have been observed during therapy in coinfected patients with preexisting cirrhosis, with the highest risk for patients with increased bilirubin and decreased platelet counts as well as with coadministration of didanosine (DDI).[9] The mitochondrial dysfunction/lactic acidosis syndrome with related deaths has occurred in patients with the coadministration of DDI with ribavirin. Coinfected patients with cirrhosis need a careful assessment of the risks and benefits of therapy and must undergo close observation while on treatment. Ribavirin and DDI should never be used in combination.

SVR (defined as undetectable HCV viral RNA 6 months after completion of HCV therapy) rates for HCV genotypes 1 and 4, with either high or low viral loads, varied from 29% in the largest trial (APRICOT) to 14% in the ACTG 5071 trial. SVR rates were markedly better in patients infected with HCV genotype 2 or 3 (60%-70%), in patients with low (< 800,000 IU/mL) HCV viral loads (60%), and in patients who adhered to 80% of their prescribed therapy (> 40% with genotype 1 and high or low viral load). Most patients in the United States have HCV genotype 1 or 4 infection and high viral loads; this patient population had a disappointing SVR rate of 18% in the APRICOT trial. Early viral load testing at 12 weeks during HCV therapy had predictive value: among those patients with a 12-week response (> 2-log reduction in HCV viral load), 50% had an eventual SVR. Although SVR remains and important goal of HCV therapy, 35% of patients who did not achieve a virologic response had significant histologic improvement when liver biopsy was repeated at 24 weeks, demonstrating the value of HCV therapy even in the absence of an SVR. Clinical trials are under way to determine the role of long-term maintenance interferon therapy in patients with histologic improvement but without an SVR.


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