[Darunavir in patients with advanced HIV and multiresistance. The POWER, DUET and BENCHMRK studies].
Darunavir is a new protease inhibitor. This drug is highly active against wild-type and multiresistant HIV strains, binds strongly to the HIV-1 protease, has extremely high affinity for the protease and, when enhanced by subtherapeutic doses of ritonavir, has a favorable resistance profile differing from that of current protease inhibitors (PIs). After determining the optimal dose, phase IIb clinical trials (POWER studies 1 and 2) observed much higher virological and immunological efficacy with darunavir than with the comparator PIs. The results of a phase III clinical trial (POWER 3) provide further support for the safety and efficacy of darunavir, and the three POWER studies demonstrate the high genetic barrier of this drug against mutations conferring resistance to other PIs, although the baseline sensitivity of darunavir and the specific mutations to this PI influence the virological response. Better therapeutic responses have been obtained when there are two or more antiretroviral drugs active against multiresistant HIV strains. The phase III trials (DUET 1 and 2), in which darunavir was administered with the new nonnucleoside reverse transcriptase inhibitor, etravirine, found that if these two drugs were administered in highly treatment-experienced patients, a large percentage showed suppression of plasma viremia and immunological recovery. These data have been supported by the results of the BENCHMARK studies, in which darunavir was included in an optimized regimen in a substantial number of patients. In these trials, when darunavir was administered with the integrase inhibitor, raltegravir, undetectable viral loads both in the raltegravir arm and in the control group were substantially improved with respect to the overall results obtained in the control group.
Arazo Garcés
Piedad
P
Servicio de Medicina Interna. Unidad de Enfermedades Infecciosas. Hospital Universitario Miguel Servet. Zaragoza. España. parazo@salud.argon.es
Omiste Sanvicente
Teresa
T
D000328:Adult; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data*; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D000069454:Darunavir; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data*; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage / Q000627:therapeutic use; D011743:Pyrimidines; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy
D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C451734:etravirine; D000068898:Raltegravir Potassium; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; D019438:Ritonavir; D000069454:Darunavir