With HIV/HBV-coinfected persons, there is an emphasis on using TDF (alone or part of an emtricitabine coformulation) as part of a suppressive HIV regimen because of the activity against both viruses and high threshold for HBV resistance. If tenofovir cannot be given, for example, because of renal insufficiency, entecavir can be used. Many experts recommend that 1 mg/day be used in all HCV/HIV-coinfected patients. Entecavir has some HIV activity and thus should only be used with a fully suppressive

HIV regimen.[15] This is true with regard to lamivudine and emtricitabine as well, which will select for HIV-resistant variants if used as HBV monotherapy. With HCV, the choice of ART is largely influenced by anticipated interactions with anti-HCV medications, including ribavirin (RBV) and the HCV protease inhibitors, boceprevir and click here telaprevir (Table 1A,B). In particular, zidovudine and ddl are avoided because of interactions BGJ398 mouse with RBV.[16, 17] Interactions between boceprevir

or telaprevir and antiretroviral agents are complex and continue to evolve as new data become available (see below). In persons with cirrhosis, the question arises of what are the most liver-friendly ART regimens. Fortunately, most antiretroviral agents that are particularly hepatotoxic are not among the currently “recommended” agents. For example, tipranavir use is discouraged in patients with advanced liver disease because of a nearly 3-fold increase risk of liver injury.[18] In addition, the so-called “d drugs” containing deoxynucleotide analogs (didanosine and stavudine) also may increase risk of hepatic steatosis and hepatoportal sclerosis, but are no longer routinely recommended.[19, 20] Drugs, such as nevirapine, that can cause hypersensitivity reactions are also best avoided in persons with cirrhosis. In persons with decompensated (Child-Pugh class C) cirrhosis, there may be a selleck chemicals preference for avoiding some protease inhibitors

(e.g., darunavir), though others (e.g., atazanavir) may be safely administered. Natural history studies have shown that HIV coinfection promotes accelerated HCV hepatic fibrosis progression, even with excellent HIV control under ART. Moreover, in those who have progressed to cirrhosis, higher rates of liver failure and death are observed, compared with patients with HCV monoinfection.[21] The mechanisms underlying accelerated hepatic fibrosis are being increasingly understood. Though immunopathogenesis as a result of virus-specific infiltrating T cells is a key driver of liver injury, it is unlikely that the dys-regulated T-cell response in HIV coinfection can alone suffice to explain the accelerated natural history. Rather, a series of perturbations brought about by HIV infection in the liver microenvironment appears to contribute to the observed phenotype.