6533b7dbfe1ef96bd126fffa

RESEARCH PRODUCT

Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL

G MadedduS RusconiA Cozzi LepriS Di GiambenedettoS BonoraA CarboneA De LucaN GianottiA Di BiagioA AntinoriA D’arminio MonforteM AndreoniG AngaranoA AntinoriF CastelliR CaudaG Di PerriM GalliR IardinoG IppolitoA LazzarinC PernoF Von SchloesserP VialeA CastagnaF Ceccherini SilbersteinA Cozzi LepriE GirardiS Lo CaputoC MussiniM PuotiA AmmassariC BalottaA BanderaP BonfantiM BorderiA CalcagnoL CalzaM CapobianchiA CingolaniP CinqueA LichtnerG MadedduF MaggioloG MarchettiS MarcotullioL MonnoS NozzaE Quiros RoldanR RossottiS RusconiM SantoroA SaracinoM ZaccarelliI FantiL GalliP LorenziniA RodanoM ShanyindeA TavelliF CarlettiS CarraraA Di CaroS GrazianoF PetroneG ProtaS QuartuS TruffaA GiacomettiA CostantiniC ValerianiC SantoroC SuardiV DonatiG VerucchiC MinardiT QuirinoC AbeliP ManconiP PianoB CacopardoB CelesiaJ VecchietK FalascaL SighinolfiD SegalaF MazzottaF VichiG CassolaC ViscoliA AlessandriniN BobbioG MazzarelloC MastroianniV BelvisiI CarammaA ChioderaA CastelliG RizzardiniA RidolfoR PioliniS SalpietroL CarenziM MoioliC TincatiC PuzzolanteA GoriG GuaraldiG LapadulaN AbresciaA ChirianniG BorgiaF Di MartinoL MaddaloniI GentileR OrlandoAntonio CascioClaudia ColombaF BaldelliD FrancisciG ParrutiT UrsiniG MagnaniM UrsittiV VulloA CristaudoG BaldinS CicaliniL GalloE NicastriR AcinapuraM CapozziR LibertoneS SavinelliA LatiniG IaianiL Fontanelli SulekovaM CecchettoF VivianiM MuraA De LucaB RossettiP CaramelloG OrofinoS BonoraM SciandraM BassettiA LonderoG PellizzerV. Manfrin

subject

0301 basic medicineMaleHIV InfectionsAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability; Microbiology (medical); Infectious DiseasesAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability; Adult; Anti-HIV Agents; Cohort Studies; Darunavir; Drug Therapy Combination; Female; HIV Infections; HIV-1; Humans; Italy; Male; Middle Aged; RNA Viral; Raltegravir Potassium; Ritonavir; Viral LoadGastroenterologyCohort StudiesAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability0302 clinical medicineMedicineNRTI-sparing regimen030212 general & internal medicineViralDarunavireducation.field_of_studyLamivudineGeneral MedicineMiddle AgedViral LoadTolerabilityAntiretroviral therapyInfectious DiseasesTolerabilityItalyCombinationRNA ViralDrug Therapy CombinationFemaleViral loadmedicine.drugAdultMicrobiology (medical)medicine.medical_specialtyEfficacyAnti-HIV Agents030106 microbiologyPopulationDarunavir/ritonavir; Raltegravir; Efficacy; Tolerability; Antiretroviral therapy; NRTI-sparing regimenSettore MED/17 - MALATTIE INFETTIVELower riskNO03 medical and health sciencesDrug TherapyInternal medicineRaltegravir PotassiumHumanseducationDarunavirRitonavirbusiness.industryDarunavir/ritonavirRaltegravirRaltegravirHIV-1RNARitonavirbusinessAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability;

description

Background: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. Objectives: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Study design: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan–Meier curves and Cox regression models were performed to estimate time to event probability. Results: We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9–31) months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL >50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1–13%] by 12 and 9% (95% CI 2–16%) by 24 months. When considering TF, we found a probability of stop/intensification/single VL > 200 copies/mL of 13% (95% CI 1–17%) and 22% (95% CI 11–33%) by 12 and 24 months. Female gender (adjusted relative hazard, ARH = 0.10; 95% CI 0.01–0.74; p = 0.024) and older age (AHR = 0.50 per 10 years older; 95% CI 0.25–0.99; p = 0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR = 52.6, 95% CI 3.6–779; p = 0.004). Conclusions: DRV/r + RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relatively low risk of VF and good tolerability after 2 years since start in an ART-experienced population. However, previous PI-failure should be a limiting factor for this strategy.

yearjournalcountryeditionlanguage
2017-01-01
10.1007/s15010-017-1018-zhttp://hdl.handle.net/10447/243751