Faculty Bibliography

Approximately 30 % of HIV-infected patients are co-infected with hepatitis C virus (HCV). After the release of highly active antiretroviral therapy, liver disease has become the leading cause of morbidity and mortality in HIV patients. Prior to 2011, HCV treatment with pegylated-interferon and ribavirin in HCV/HIV co-infected patients only allowed 14-38 % of patients with HCV genotype 1 to achieve a sustained virologic response (SVR). Additionally, treatment was commonly discontinued as a result of adverse events. Recently, simeprevir and sofosbuvir have been approved by the US Food and Drug Administration (FDA) for HCV mono-infection. Sofosbuvir has been given FDA approval in co-infected patients offering unprecedented SVR rates and the potential for interferon-free therapy. HCV therapies that are in the pipeline offer improved treatment times, safety profiles, and rates of SVR. Despite these improvements, several new issues including adherence, drug-drug interactions with antiretroviral therapies, adverse events, resistance, and patient selection may complicate therapy. This article reviews the current status of direct-acting antivirals (DAA)-containing regimens for HIV/HCV co-infected patients in the USA. New results investigating telaprevir and boceprevir are also discussed as they are relevant for locations where new DAAs are not available. The impact future interferon-free therapies may have on co-infected patients is also discussed.

Since the approval of the first direct-acting antiviral agents (DAAs), treatment for hepatitis C virus (HCV) has undergone significant transformation. A new milestone in the treatment of HCV, the approval of the first interferon-free regimens, could be achieved by the end of 2013. For patients with HCV who have absolute or relative contraindications to pegylated-interferon or have failed the currently available treatments, the arrival of new regimens will have a major impact on long-term outcomes. The combinations of DAAs in trials are numerous, and many have demonstrated sustained virologic response rates higher than 90 %. These improvements have also been observed in previous null responders and patients who failed telaprevir- or boceprevir-based regimens. Some specific subpopulations may not be perfectly served by interferon-free regimens, such as patients with genotypes 1a or 3 or cirrhosis, whereas others, such as HIV-infected patients or transplant patients, will definitively benefit from regimens with a lower burden of side effects. This paper reviews the interferon-free regimens currently in phase II or III for which sustained virologic response data are available and discusses the successes and potential pitfalls of these regimens.

Noncirrhotic portal hypertension (NCPH) is a rare but important clinical entity in human immunodeficiency virus (HIV) populations. The purpose of this study was to describe the clinical factors associated with the condition in an effort to formulate a diagnostic algorithm for easy and early diagnosis. We performed a multicenter, retrospective case-control study of 34 patients with NCPH and 68 control HIV patients. The study found that thrombocytopenia, splenomegaly, didanosine use, elevated aminotransferases, and an elevated alkaline phosphatase level were all significantly more prevalent in the NCPH cohort. Using these easily available clinical parameters, we developed an algorithm for early diagnosis of NCPH in HIV.

Liver disease, specifically cirrhosis, is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The diagnosis of early cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients may be challenging. The development of noninvasive methods for fibrosis assessment empowers the infectious disease specialist to diagnose advanced fibrosis or cirrhosis. Early diagnosis is essential to enroll patients in screening programs for esophageal varices and hepatocellular carcinoma. Cirrhosis may also modify decisions about treatment of both HIV and HCV, including vaccination, medications chosen, and referral for liver transplant.

BACKGROUND: There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal. METHODS: We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment. RESULTS: In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received