[Role of the new molecules in antiretroviral therapy. Position of raltegravir].
Antiretroviral rescue therapy has been revolutionized by the development of new drugs in the last few years: enfuvirtide (a fusion inhibitor), tipranavir/ritonavir (a high genetic barrier protease inhibitor), darunavir/ritonavir (a high genetic barrier protease inhibitor), etravirine (a non-nucleoside reverse transcriptase inhibitor active against nevirapine- and efavirenz- resistant HIV), maraviroc (a CCR5 coreceptor inhibitor) and raltegravir (an integrase inhibitor). The use of these drugs in rescue regimens has allowed the goal of antiretroviral rescue therapy to be the same as that in treatment naive-patients: to achieve a viral load lower than 50 copies of RNA of HIV/ml. Raltegravir is the first integrase inhibitor available for clinical use in Spain. This drug is primarily metabolized through UGT1A1-mediated glucuronidation and consequently has a low potential for interactions with drugs metabolized by the cytochrome P450 pathway. Raltegravir has been demonstrated to have high efficacy in two large clinical trials of rescue therapy, especially when combined with darunavir/ritonavir and enfuvirtide. Preliminary data suggest that raltegravir could also be an effective drug in treatment-naive patients and as substitution therapy in patients with toxicity due to boosted protease inhibitor therapy. The drug's unusual mechanism of action has reopened the possibility of a positive effect on latent HIV reservoirs.
Arribas
José R
JR
Consulta de Medicina Interna II (Unidad VIH), Hospital La Paz, Madrid, España. jrarribas.hulp@salud.madrid.org
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000008:administration & dosage / Q000627:therapeutic use; D000069454:Darunavir; D024921:Drug Resistance, Multiple, Viral; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005544:Forecasting; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000077592:Maraviroc; D009570:Nitriles; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D011724:Pyridazines / Q000008:administration & dosage / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D011743:Pyrimidines; D011753:Pyrones / Q000008:administration & dosage / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000494:pharmacology / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D019428:HIV Integrase Inhibitors; D009570:Nitriles; D010446:Peptide Fragments; D011724:Pyridazines; D011725:Pyridines; D011743:Pyrimidines; D011753:Pyrones; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D014230:Triazoles; C451734:etravirine; D000077560:Enfuvirtide; D000068898:Raltegravir Potassium; D000077592:Maraviroc; D000069454:Darunavir; C107201:tipranavir