Raltegravir: new Drug. Alternative to enfuvirtide/darunavir in multidrug-resistant HIV.
(1) HIV-infected patients who have exhausted most existing antiretroviral treatment options benefit when enfuvirtide or darunavir is added to an optimised multidrug regimen based on the resistance profile; (2) Raltegravir is the first HIV integrase inhibitor to arrive on the market. It was authorised in 2007 in the European Union for patients with multiple antidrug failure; (3) A dose-finding study and two double-blind placebo-controlled trials showed that when raltegravir is added to an optimised antiretroviral regimen about two-thirds of patients achieve undetectable viral load, compared to about one-third of patients treated with an optimised regimen plus placebo. Data are currently limited to 48 weeks. In contrast, adding raltegravir barely increases the efficacy of treatments already containing enfuvirtide and darunavir. Half of patients in whom treatment failed developed viral resistance to raltegravir during these trials; (4) In previously untreated patients, a double-blind controlled trial showed no statistically significant difference in viral load at 48 weeks between raltegravir/tenofovir/lamivudine and efavirenz/tenofovir/lamivudine, but there were only about 40 patients in each group; (5) The adverse effects of raltegravir are poorly documented. In vitro findings, along with the limited clinical data available, point to a potential risk of autoimmune and lymphoproliferative disorders in the long term. (6) Raltegravir is not metabolised by the cytochrome P450 enzyme system, meaning that it should have fewer pharmacokinetic interactions than darunavir. But raltegravir is sensitive to enzyme inducers, which activate its metabolism; (7) Raltegravir is taken orally, twice a day, either during or between meals; (8) In practice, raltegravir is an option for HIV-infected patients with multiple antiretroviral drug failure and few remaining treatment options. It represents an alternative to the darunavir/enfuvirtide combination, and has the advantage of being more convenient to use. Assessment must continue, however, especially in order to identify long-term adverse effects.
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D002986:Clinical Trials as Topic; D017277:Drug Approval; D018432:Drug Resistance, Multiple; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005060:Europe; D006678:HIV / Q000187:drug effects; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019429:Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D019429:Integrase Inhibitors; D010446:Peptide Fragments; D011760:Pyrrolidinones; D013449:Sulfonamides