title: Lopinavir plasma concentrations and virological outcome with lopinavir-ritonavir monotherapy in HIV-1-infected patients.
abstract: There is significant intra- and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI(95)], 75.3 to 89.3%). Virological efficacy was independent of LPV plasma concentrations even when LPVr was given once daily. An adherence of <90% (HR, 4.4 [CI(95), 1.78 to 10.8; P = 0.001]) and the presence of blips in the preceding 12 months (HR, 3.06 [CI(95), 1.17 to 8.01; P = 0.022]) were the only variables independently associated with time to VF. These findings suggest that the LPV concentrations achieved with the standard doses of LPVr are sufficient to maintain virological control during monotherapy and that measurement of LPV concentrations is not useful for predicting virological outcome. Tight control of viral replication in the previous months and strict adherence throughout the mtLPVr regimen could improve the virological efficacy of this maintenance regimen.
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain. lflopez@us.es
authors.forename: Luis F
authors.initials: LF
authors.lastname: Lopez-Cortes
authors.forename: Rosa
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez-Rivas
authors.forename: Amparo
authors.initials: A
authors.lastname: Lluch
authors.forename: Alicia
authors.initials: A
authors.lastname: Gutierrez-Valencia
authors.forename: Almudena
authors.initials: A
authors.lastname: Torres-Cornejo
authors.forename: Omar J
authors.initials: OJ
authors.lastname: Benmarzouk-Hidalgo
authors.forename: Pompeyo
authors.initials: P
authors.lastname: Viciana
mesh_terms: D000328:Adult; D000368:Aged; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir