title: [Data on rilpivirine in treatment-naïve patients. Lessons from ECHO, THRIVE and STaR].
abstract: Rilpivirine (RPV) is a new, second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) that has been recently approved for use in the initial antiretroviral therapy (ART) of treatment-naïve HIV-infected patients, combined with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). The approved dose is 25mg once daily with food. RPV has been assessed in a phase IIb study (TMC278-C204) and in three phase III trials (ECHO, THRIVE and STaR). In all of them, RPV was compared with the gold standard, efavirenz (EFV); these studies enrolled a large number of patients (n=1,349 on RPV). RPV was non-inferior to EFV at 48 and 96 weeks. In all the studies and study arms, the tolerability of RPV was better than that of EFV, especially for neuropsychiatric adverse effects, rash, and lipid profile. An analysis of the combined data from the ECHO and THRIVE trials showed marked differences, depending on baseline viral load. The therapeutic efficacy of RPV was superior to that of EFV in patients with a baseline viral load ≤ 100,000 copies/mL, due to a similar virological efficacy and a better tolerability profile. However, in patients with a baseline viral load ≥ 100,000 copies/mL, virological failure was more frequent in the RPV arm, especially in patients with a viral load ≥ 500,000 copies/mL. Emerging resistance mutations to RPV were commonly detected in patients with virological failure, especially in those with a higher baseline viral load. In view of these results, the European Medications Agency and the US Food and Drug Administration have approved the use of RPV in treatment-naïve patients with a baseline viral load ≤ 100,000 copies/mL. Some treatment guidelines have already included RPV among their recommendations. The guidelines of the US Department of Health and Human Services (DHSS) and the International Antiviral Society-USA ((IAS-USA), while awaiting additional data, consider RPV-based regimens as an alternative regimen. The Gesida guidelines consider RPV to be among the preferred regimens in patients with a viral load ≤ 100,000 copies/mL. Recent data from the STaR trial, which used fixed drug combinations, have shown the non-inferiority of RPV with respect to EFV, less virological failure and less emergence of resistance mutations with RPV use, irrespective of baseline viral load. In summary, efficacy and safety data suggest that RPV plus 2 NRTI is an effective and safe initial antiretroviral regime.
authors.affiliation: Unitat de Malalties Infeccioses, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España.
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Esteban
authors.initials: E
authors.lastname: Ribera
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data*; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D055118:Medication Adherence; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data*; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068696:Rilpivirine; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D000068696:Rilpivirine; C098320:efavirenz
keywords: Adverse effects; Efavirenz; Efficacy; Eficacia; Inhibidores de la transcriptasa inversa no; NNRTI; NRTI; Naïve; Resistance mutations; Resistencias; Rilpivirina; Rilpivirine; Safety; Seguridad; Tratamiento antirretroviral de inicio; Virological failure; análogos de nucleósidos