title: [Resistance profile of rilpivirine].
abstract: Rilpivirine (RPV) is a new second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) approved for use in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) as initial therapy in treatment-naïve HIV-1-infected patients with a baseline viral load ≤100,000 copies/mL. RPV is a diarylpyrimidine derivative with potent in vitro activity against multiple HIV-1 variants with resistance mutations to first-generation NNRTI such as K103N. In vitro studies and phase III clinical trials have allowed the identification of 16 mutations associated with resistance to RPV K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L. The risk of virologic failure in patients receiving RPV plus 2 NRTI with plasma viral load ≤ 100,000 copies/mL is low, but a high percentage of patients failing RPV develop resistance mutations to both RPV and NRTI. The most common resistance mutation that emerges in this setting is E138K. This mutation is usually associated with M184I due to a double compensatory effect of this combination, which confers resistance to RPV, as well as to lamivudine and emtricitabine. The emergence of RPV resistance confers cross-resistance to all NNRTI and, importantly, high percentages of cross-resistance to etravirine.
authors.affiliation: Unidad de VIH, Servicio de Enfermedades Infecciosas, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, España. Electronic address: aimaz@bellvitgehospital.cat.
authors.forename: Arkaitz
authors.initials: A
authors.lastname: Imaz
authors.forename: Federico
authors.initials: F
authors.lastname: García
authors.forename: Silvana
authors.initials: S
authors.lastname: di Yacovo
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D002478:Cells, Cultured; D017326:Clinical Trials, Phase III as Topic; D004353:Drug Evaluation, Preclinical; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D015337:Multicenter Studies as Topic; D009154:Mutation; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010641:Phenotype; D017354:Point Mutation; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000068696:Rilpivirine; D013601:T-Lymphocytes / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine
keywords: HIV-1; HIV-1 resistance; HIV-1-resistance mutations; Mutaciones de resistencia a VIH-1; Resistencia a antirretrovirales; Rilpivirina; Rilpivirine; VIH-1