6533b81ffe1ef96bd1277af0
RESEARCH PRODUCT
Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort
L. TaramassoP. LorenziniA. Di BiagioM. LichtnerG. MarchettiR. RossottiG. LapadulaA. Cozzi-lepriF. VichiA. AntinoriS. BonoraA. D'arminio MonforteA D'arminio Monforte Icona Foundation Study Group:A AntinoriM AndreoniA CastagnaF CastelliR Cauda G Di PerriM GalliR IardinoG IppolitoA LazzarinG C MarchettiG Rezza F Von SchloesserP Viale A D'arminio MonforteA AntinoriA CastagnaF Ceccherini-silbersteinA Cozzi-lepriE Girardi S Lo CaputoC MussiniM PuotiC F PernoA AntinoriF BaiC BalottaA BanderaS BonoraM BorderiA CalcagnoA CapettiM R CapobianchiA CastagnaF Ceccherini-silbersteinS CicaliniA CingolaniP CinqueA Cozzi-lepri A D'arminio Monforte A De Luca A Di BiagioE GirardiN GianottiA GoriG GuaraldiG LapadulaM Lichtner S Lo CaputoG MadedduF MaggioloG MarchettiL MonnoC MussiniS NozzaC F PernoC PinnettiM PuotiMaria Eugenia Quiros RoldanR RossottiS RusconiM M SantoroA SaracinoL SarmatiA Cozzi-lepriI FantiL GalliP LorenziniA Rodano'M MacchiaA TavelliF CarlettiS Carrara A Di CaroS GrazianoF PetroniG ProtaS TruffaA GiacomettiA CostantiniV BarocciG AngaranoL MonnoE MilanoF MaggioloC SuardiP VialeV DonatiG VerucchiF CastelnuovoC MinardiMaria Eugenia Quiros RoldanB MenzaghiC AbeliB CacopardoB CelesiaJ VecchietK FalascaA PanS LorenzottiL SighinolfiD SegalaP BlancF VichiG CassolaC ViscoliA AlessandriniN BobbioG MazzarelloM LichtnerS VitaP BonfantiC MolteniA ChioderaP MiliniG NunnariG Pellicanò A D'arminio MonforteM GalliA LazzarinG RizzardiniM PuotiA CastagnaE S CannizzoM C MoioliR PioliniD BernacchiaS SalpietroC TincatiC MussiniC PuzzolanteC MigliorinoG LapadulaV SangiovanniG BorgiaV Esposito F Di MartinoI GentileV RizzoA M CattelanS MarinelloA CascioM TrizzinoF BaldelliE SchiaroliG ParrutiF SozioG MagnaniM A UrsittiM AndreoniA AntinoriR CaudaA CristaudoV VulloR AcinapuraD MoscheseM CapozziA MondiA Cingolani M Rivano CapparucciaG IaianiA LatiniR GagliardiniM M PlazziS SavinelliA VergoriM CecchettoF VivianiG Madeddu A De VitoB RossettiF MontagnaniA Franco R Fontana Del VecchioD Francisci C Di GiuliP Caramello G Di PerriS BonoraG C OrofinoM SciandraM BassettiA LonderoG PellizzerV ManfrinG StarniniA Ialungosubject
0301 basic medicineMaleIntegrase inhibitorHepatitis B Surface AntigenHIV Infections0302 clinical medicineRisk Factorshivh epatitis c rna surface antigens follow-up homosexuality integrase inhibitors hepatitis b virus hepatitis b virus measurement hiv infections hepatotoxicity hepatitis c virus coinfection nucleoside reverse transcriptase inhibitors non-nucleoside reverse transcriptase inhibitors cox proportional hazards models baseline value liver enzyme raltegravirPharmacology (medical)HIV Infection030212 general & internal medicineProspective StudiesProspective cohort studyCoinfectionIncidence (epidemiology)Liver DiseaseIncidenceLiver Diseasesvirus diseasesHepatitis CMiddle AgedHepatitis CReverse Transcriptase InhibitorInfectious DiseasesCohortCoinfectionPopulation studyRegression AnalysisReverse Transcriptase InhibitorsFemalemedicine.drugHumanMicrobiology (medical)Adultmedicine.medical_specialtyAnti-HIV AgentsRegression AnalysiNO03 medical and health sciencesInternal medicinemedicineHumansHIV Integrase InhibitorsHIV Protease InhibitorPharmacologyHepatitis B Surface Antigensbusiness.industryAnti-HIV AgentHIV ARTHIV Protease Inhibitorsmedicine.diseaseRaltegravir030112 virologyHIV Integrase InhibitorProspective StudieHIV-1businessAdult Anti-HIV Agents Coinfection Female Hepatitis B Surface Antigens Hepatitis C HIV Infections HIV Integrase Inhibitors HIV Protease Inhibitors HIV-1 Humans Incidence Liver Diseases Male Middle Aged Prospective Studies Regression Analysis Reverse Transcriptase Inhibitors Risk Factorsdescription
AbstractObjectivesTo evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017.Patients and methodsIn total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases of ≥2.5× upper limit of normal (ULN) for patients with normal baseline values or ≥2.5× baseline for patients with higher baseline values.ResultsOne hundred and eighty-three LEE occurred over 20722 patient-years of follow-up. After adjusting for the main confounders, the risk of LEE halved with INSTIs compared with NNRTIs (HR 0.46, 95% CI 0.25–0.86), with a significant reduction in the raltegravir group (HR 0.11, 95% CI 0.02–0.84 using the NNRTI class as reference). HRs for LEE were significantly higher in subjects with HBV or HCV coinfection, in patients with poorly controlled HIV infection and in those who acquired HIV through homosexual transmission.ConclusionsIn our study, INSTI use almost halved the risk of LEE compared with other regimens. This finding could be particularly important for choosing ART in patients with risk factors for liver toxicity such as HCV and HBV coinfections.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-01-01 |