6533b86cfe1ef96bd12c8061
RESEARCH PRODUCT
Low Rate of Virological Failure and Maintenance of Susceptibility to HIV-1 Protease Inhibitors with First-Line Lopinavir/Ritonavir-Based Antiretroviral Treatment in Clinical Practice
Mc ProsperiM ZazziG PunziL MonnoG ColaoP CorsiS Di GiambenedettoG MeiniV GhisettiS BonoraM PecorariMr GismondoP BagnarelliT CarliA De Luca Arca Collaborative GroupA GiacomettiL ButiniR Del GobboS MenzoD TacconiG CorbelliS ZanussiL MonnoG PunziF MaggioloA CallegaroL CalzaMc ReP RaffaeleP TurconiA MandasS TiniA ZoncadaE PaoliniG AmadioL SighinolfiG ZuccatiM MorfiniR ManettiP CorsiL GalliM Di PietroF BartalesiG ColaoA TostiA Di BiagioM SettiB BruzzoneG PencoM TrezziA OraniR PardelliM De GennaroA ChioderaA ScalziniL PalvariniP AlmiG TodaroA MonforteP CicconiS RusconiMr GismondoMr GismondoV MicheliMl BiondiN GianottiA CapettiP MeravigliaE BoeriC MussiniM PecorariA SoriaL VecchiM SantirocchiD BrustiaP RavaniniF Dal BelloN RomanoS MancusoC CalzettiR MaseratiG FiliceF BaldantiD FrancisciG ParrutiE PolilliD SacchiniC MartinelliRita Consolinisubject
MaleLopinavir/ritonavirHIV Infectionsboosted protease inhibitorLopinavirCohort Studies0302 clinical medicineAntiretroviral Therapy Highly Activevirologic failureHIV InfectionTreatment Failure030212 general & internal medicinePyrimidinone0303 health scienceseducation.field_of_studylopinavir/ritonavirLopinavirViral LoadResistance mutationfirst-line antiretroviral therapyReverse Transcriptase Inhibitor3. Good healthTreatment OutcomeInfectious DiseasesRNA ViralReverse Transcriptase InhibitorsMedicineDrug Therapy CombinationFemaleSurvival AnalysiViral loadHumanmedicine.drugAnti-HIV AgentsPopulationPyrimidinones.Settore MED/17 - MALATTIE INFETTIVEEmtricitabinehuman immunodeficiency virus type 103 medical and health sciencesVirologyDrug Resistance Viralantiretroviral drug resistancemedicineHumansProtease inhibitor (pharmacology)educationHIV Protease InhibitorRitonavir030306 microbiologybusiness.industryAnti-HIV AgentHIV Protease InhibitorsSurvival AnalysisVirologyHIV-1RitonavirCohort Studiebusinessdescription
Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P 500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. © 2010 Wiley-Liss, Inc.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-10-27 |