Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients

Inclusion Criteria

• •Age ≥ 18
• •Documented HIV-1 infection, hepatitis B or C co-infection is allowed
• •Plasma viral load at screening visit below 50 copies per mL for at least 6 months
• •Patient with severe liver failure (Meld Score ≥ 15 and/or refractory ascites and/or haemorrhage of digestive tract and/or hepatic encephalopathy) for taking part into period 1
• •Patient eligible for the liver transplant waiting list or immediate post transplantation for taking part into period 2
• •Abstinence from alcohol intake for at least 6 months (WHO norm)
• •Withdrawal from intravenous drug use for at least 6 months (methadone substitution is permitted)
• •No ongoing class C opportunistic infection (1993 CDC classification)
• •Patient whose clinical and immunovirological condition allows triple therapy with raltegravir + 2 NRTI or raltegravir + NRTI + enfuvirtide
• •Patient whose HIV population, according to cumulative genotypes carried out on viral RNA together with treatment history (if available and interpreted as per the ANRS-AC11 algorithm version no.19) does not present a profile of mutations associated with resistance to raltegravir and is sensitive to at least two fully active\* agents selected among nucleoside/nucleotide reverse transcriptase analogs NRTI (abacavir, lamivudine, emtricitabine, tenofovir) or enfuvirtide
• •\*An ARV agent is considered to be fully active if the cumulative genotypes do not show any mutation associated with resistance or any mutation associated with "possible resistance"
• •Patient not having experienced viral escape during treatment combining 3TC, FTC or raltegravir
• •Patient registered with or covered by a social security scheme
• •For women of child-bearing potential, use of a barrier contraceptive method during sexual intercourse and negative pregnancy test (plasma ß-HCG ) at screening visit
• •Informed consent form signed at screening visit at the latest
• •Ongoing treatment with interferon-alpha or ribavirin for hepatitis C
• •Concomitant medication including one or more agents liable to induce UGT1A1 and reduce raltegravir concentrations:
• •* anti-infective agents: rifampicin/rifampin
• •* psychotropic/antiepileptic agents: phenytoin, phenobarbital, carbamazepine
• •* steroidal anti-inflammatory drug: dexamethasone