Long-term efficacy and safety of raltegravir in the management of HIV infection

Abstract

Raltegravir is an integrase strand-transfer inhibitor approved for the treatment of HIV infection. It was the first medication in a novel class of antiretroviral agents to be approved for use in the United States in 2007. Raltegravir exhibits potent activity against wild-type HIV-1, but resistance development has been noted through three different pathways. It is metabolized primarily through uridine diphosphate glucuronosyltransferase 1A1 and has a single inactive glucuronide metabolite. Raltegravir is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes and exhibits low potential for drug–drug interactions; however, strong uridine diphosphate glucuronosyltransferase 1A1 inhibitors or inducers can alter the pharmacokinetics of raltegravir. It is well tolerated, and the most commonly reported adverse effects include headache, nausea, and diarrhea. Serious adverse effects with raltegravir are rare but include rhabdomyolysis and severe skin and hypersensitivity reactions. It has been approved for use in both treatment-naïve and treatment-experienced patients and is a preferred first-line agent in both United States and European HIV treatment guidelines. Although initial approval was granted on 48-week data, 5-year clinical data have recently been published. This article reviews the data supporting long-term efficacy and safety of raltegravir in the treatment of HIV infection.

A phase II baseline versus treatment study to determine the efficacy of raltegravir (Isentress) in preventing progression of relapsing remitting multiple sclerosis as determined by gadolinium-enhanced MRI: The INSPIRE study

“…Raltegravir (Isentress®, Merck and Co., Inc., Whitehouse Station, NJ, USA) is a twice daily oral integrase strand transfer inhibitor approved for treating HIV infection in 2007, in combination with other antiretroviral agents. Its safety profile has been confirmed during more than 10 years of use (21). Raltegravir was chosen as it has a proven safety profile and, as there are not available in-vitro data on the effectiveness of antiretroviral therapy in HERVs, we decided that a single agent would be appropriate for an initial investigation as was also the case in the initial clinical studies of HIV.…”

Selective and rapid determination of raltegravir in human plasma by liquid chromatography–tandem mass spectrometry in the negative ionization mode

“…Although the area under the plasma-time curve (AUC) increases by about 19% with a high fat meal, RAL can be given without regard to food [1] . The time required to reach peak plasma concentration was ~2 h, which was almost double as observed by Kassahun et al [9] with 200 mg dose of RAL in healthy subjects.…”

“…Raltegravir (RAL), a hydroxypyrimidinone carboxamide derivative, is an integrase strand-transfer inhibitor (INSTI) used in the treatment and management of human immunodeficiency virus (HIV) infection [1] . It was first approved by USFDA in 2007 for the treatment of HIV treatment-experienced patients [2] .…”

Recent Advances in the Discovery of Small-Molecule Inhibitors of HIV-1 Integrase

“…RAL ( 1 ) was the first in the class of INIs being approved by the FDA for the treatment of HIV infection. It was initially approved for use in antiretroviral treatment-experienced adult patients [ 55–58 ]. Although it was discovered by Merck from the evolution of DKAs in their HCV polymerase program, the compound is completely inactive on the HCV polymerase.…”

“…In treatment-naive patients with plasma HIV-1 RNA levels greater or equal to 5000 copies/ml and CD4 T-cell counts greater or equal to 100 cells/mm, the drug leads to plasma HIV-1 RNA levels less than 400 copies/ml in 85–98% of patients and less than 50 copies/ml in 85–95% of patients by 24 weeks of treatment [ 60 ]. In addition to the high clinical efficacy, initial use of RAL also showed good tolerability, a favorable safety profile and absence of significant drug–drug interactions [ 55 , 58 ]. It is unique mechanism of action at time of approval made RAL a great addition for the treatment of patients with extensive drug resistance to other anti HIV drugs such as inhibitors of HIV RT and PR.…”