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The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

In this case report, we examine the impact of a simplified two-drug highly active antiretroviral therapy (HAART) regimen of raltegravir and lamivudine in a patient co-infected with human immunodeficiency virus (HIV) and hepatitis C, D and B viruses (HCV/HDV/HBV) under immunosuppressive therapy after liver transplantation. Pharmacokinetic interactions between integrase inhibitors and immunosuppressant drugs are described. Raltegravir, the first integrase inhibitor, associated with lamivudine, was introduced because its metabolism does not interfere with immunosuppressant therapy. During post-orthotopic liver transplantation follow-up, the patient's transaminases level increased and his antiretroviral therapy (HAART) of tenofovir/emtricitabine and fosamprenavir was changed, due to suspected drug toxicity. After seven months of follow-up, the patient showed good tolerance, good viro-immunological control with undetectable HIV viraemia and stable concentrations of immunosuppressive drugs. This case indicates that the combination of raltegravir and lamivudine is an optimal and effective strategy because it resulted in an important reduction of hepatic transaminases in a patient with very critical clinical conditions.

Maraviroc, originally designated UK-427857, is a small molecule and the first oral antiretroviral drug in the CCR5 receptor antagonist class used in the treatment of HIV infection. This drug, classed as an entry inhibitor, was developed by the drug company Pfizer in its United Kingdom laboratory located in Sandwich. On April 24, 2007, the US Food and Drug Administration (FDA) advisory panel reviewing maraviroc's new drug application, unanimously recommended approval for the new drug (1), and the drug received full FDA approval on August 6, 2007, for use in treatment experienced patients. Maraviroc is extensively metabolized by CYP3A4, with renal clearance accounting for approximately 23% of total clearance and it has been shown to achieve an undetectable HIV-1 RNA level in clinically advanced, class three antiretroviral treatment-experienced adults with evidence of CCR5-tropic HIV-1 replication despite ongoing antiretroviral therapy. It is well tolerated and its development is responding to a desperate need for new classes of antiretroviral agents that can target novel steps of the HIV lifecycle and not share cross-resistance with currently available therapy (2). Our case report aims to explain the impact of maraviroc co-administered with agents from all classes of anti-retroviral therapy in an HIV-1 experienced patient with six years of antiretroviral experience.