bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplification to Stribild vs continuation of RTV‐boosted DRV with FTC and TDF in virologically suppressed HIV adults: a STRATEGY‐PI subgroup analysis
Authors: Arribas Jose , Rizzardini Giuliano , Arasteh Keikawus , Zurawski Christine , Dietz Craig , Pontani Dennis , Garner Will , Nguyen Thai 
Published: November 2014

IntroductionSimplification to Stribild (STB) was statistically superior to continuation of a ritonavir‐boosted protease inhibitor (PI+RTV) with emtricitabine and tenofovir DF (FTC/TDF) at week (W) 48 in virologically suppressed HIV adults (1). We report the W48 efficacy and safety of STB versus RTV‐boosted darunavir (DRV) with FTC/TDF in suppressed subjects.Material and MethodsVirologically suppressed subjects on PI+RTV with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB vs continue their PI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV‐1 RNA <50 copies(c)/mL at W48 by FDA snapshot algorithm (12% non‐inferiority margin). Subgroup analysis by PI use (DRV [173], atazanavir [174], lopinavir [72], Other PI [13]) at screening was pre‐specified.ResultsFour hundred twenty‐nine subjects were randomized and treated (mITT set). In the DRV subgroup, 113 switched to STB; 60 continued a RTV‐boosted DRV with FTC/TDF. At W48, 95% STB versus 92% DRV maintained HIV‐1 RNA <50 c/mL. No emergent resistance was detected in either group. Median increases from baseline in CD4 count at week 48 (cells/µL): 28 STB versus 29 DRV (p=0.81). Discontinuations due to adverse events were 3% STB versus 2% DRV; one case of isolated decrease in eGFR in the DRV group and no cases of proximal renal tubulopathy in either group. There were statistically significant decreases in the frequency of diarrhoea reported on the HIV Symptom Index at week 4 to week 48 compared to baseline after switching to STB. There was a greater but non‐progressive decrease from baseline in eGFR in the STB vs DRV group; median changes (mL/min) at week 48: −8.5 vs −0.6, consistent with the known cobicistat inhibition of renal creatinine secretion. Switch to STB was associated with a higher treatment ease (convenience, flexibility, demand, lifestyle, understanding) score (range: −15 to 15) at week 4 (median: 12 vs 9; p=0.006) and week 24 (median: 13 vs 8; p=0.001).ConclusionsIn this small group of virologically suppressed subjects, simplification to STB versus continuation of a RTV‐boosted DRV with FTC/TDF was safe, well‐tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use.
Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV‐infected patients: 24‐weeks interim analysis from ATLAS‐M trial
Authors: Fabbiani Massimiliano , Di Giambenedetto Simona , Quiros‐Roldan Eugenia , Latini Alessandra , Vullo Vincenzo , Antinori Andrea , Castagna Antonella , Orofino Giancarlo , Francisci Daniela , Grilli Elisabetta , Madeddu Giordanu , Grima Pierfrancesco , Rusconi Stefano , Del Pin Barbara , Mondi Annalisa , Borghetti Alberto , Focà Emanuele , Colafigli Manuela , De Luca Andrea , Cauda Roberto 
Published: November 2014

IntroductionWe report interim 24‐weeks efficacy data of ATLAS‐M trial, a phase IV, multicentre, open‐label, randomized study designed to show 48‐weeks, non‐inferior efficacy (margin of −12%) of treatment simplification to atazanavir/ritonavir (ATV/r)+lamivudine (3TC) versus maintaining 3‐drugs ATV/r‐based cART.MethodsSubjects on ATV/r+2 NRTIs, without previous treatment failure (TF), with HIV‐RNA <50copies/mL for >3 months and CD4>200 cells/mm3 for >6 months were eligible. At baseline, patients were randomized to switch to ATV/r+3TC (arm one) or to maintain the original 3‐drug regimen (arm two). Primary endpoint: proportion of patients free of TF at week 48. TF was defined as treatment modification for any reason, including virological failure (VF=two consecutive HIV‐RNA>50 copies/mL or a single value >1000 copies/mL). Enrollment of 266 patients was planned.ResultsA total of 266 patients (78% males, median age 44 years, median CD4 603 cells/µL, 79% treated with a tenofovir‐containing backbone) were enrolled. At the time of analysis, 24 weeks data were available for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 24 weeks, at the intention to treat analysis the proportion of patients free of TF was 91.7% (95% CI 85.8–97.6) and 85.1% (95% CI 77.6–92.6) in arm one and two, respectively (difference +6.6%, 95% CI −2.9/+16.1). VF was observed in two patients randomized to arm one (one at baseline, before treatment simplification) and one to arm two without resistance mutations. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 24, patients in arm one showed a greater increase in CD4 (mean change +90 vs +10 cells/µL, p=0.007). A greater increase in total cholesterol (+18 vs −2 mg/dL, p<0.001), HDL (+4 vs +0 mg/dL, p=0.001) and LDL (+12 vs +0 mg/dL, p=0.001) was also observed in arm one without differences in other lipid parameters. Renal function showed a significant improvement in arm one (mean change in eGFR +5 vs −2 mL/min/1.73m2 in arm two, p=0.001). No significant differences in bilirubin levels or other laboratory parameters were observed between the two arms.ConclusionsThis interim analysis suggests a 24‐weeks non‐inferior efficacy of treatment simplification to ATV/rit+3TC as compared to continuation of ATV/rit +2 NRTI in virologically suppressed patients. Follow‐up until 48‐weeks is scheduled to confirm these data.
Monotherapy with darunavir/ritonavir is effective and safe in clinical practice
Authors: Pasquau Juan , López‐Cortés Luis , Isabel Mayorga Maria , Viciana Pompeyo , del Mar Arenas María , José Ríos Maria , Hernández‐Quero José , Castaño Manuel , Dolores Merino María , Márquez Manuel , Vergara Antonio , Terrón Alberto , Téllez Francisco , Hidalgo‐Tenorio Carmen 
Published: November 2014

IntroductionMonotherapy against HIV has undoubted theoretical advantages and has good scientific fundaments. However, it is still controversial and here we will analyze the efficacy and safety of MT with darunavir with ritonavir (DRV/r) on patients who have received this treatment in our hospitals.Materials and MethodsObservational retrospective study that includes patients from 10 Andalusian hospitals that have received DRV/r in MT and that have been followed over a minimum of 12 months. We carried out a statistical descriptive analysis based on the profile of patients who had been prescribed MT and the efficacy and safety that were observed, paying special attention to treatment failure and virological evolution.ResultsDRV/r was prescribed to 604 patients, of which 41.1% had a CD4 nadir <200/mmc. 33.1% had chronic hepatitis caused by HCV, had received an average of five lines of previous treatment and had a history of treatment failure to analogues in 33%, to non‐analogues 22 and protease inhibitors (PI) in 19.5%. 76.6% proceeded from a previous treatment with PI. The simplification was the main criteria for the instauration of MT in the 81.5% and the adverse effects in the 18.5%. We managed to maintain MT in 84% of cases, with only 4.8% of virological failure (VF) with viral load (VL) >200 c/mL and 3.6% additional losses due to VF with VL between 50 and 200 copies/mL. Thirty three genotypes were performed after failure without findings of resistance mutations to DRV/r or other IPs. Only 23.7% of patients presented some blips during the period of exposition to MT. Eighty seven percent of all determinations of VL had <50 copies/mL, and only 4.99% had >200 copies/mL. Although up to 14.9% registered at some point an AE, only 2.6% abandoned MT because of AE and 1.2% because of voluntary decision. Although the average of total and LDL cholesterol increases 10 mg/dL after 2 years of follow‐up, so did HDL cholesterol in 3mg/dL and the values of triglycerides (−14 mg/dL) and GPT (−6 UI/mL) decreased. The average count of CD4 lymphocytes increased from 642 to 714/mm3 at 24 weeks.ConclusionsIn a very broad series of patients obtained from clinical practice, data from clinical trials was confirmed: MT with DRV as a de‐escalation strategy is very safe, it's associated to a negligible rate of adverse effects and maintains a good suppression of HIV replication. VF (with >50 or >200 copies/mL) is always under 10% and in any case without consequences.
ACTG‐HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO‐STR study
Authors: Podzamczer Daniel , Rozas Nerea , Domingo Pere , Ocampo Antonio , Van den Eynde Eva , Deig Elisabeth , Vergara Antonio , Knobel Hernando , Pasquau Juan , Antela Antonio , Crespo Manuel , Clotet Bonaventure , Muñoz Jessica , Fernandez Pedro , Geijo Paloma , Rodríguez de Castro Eduardo , Diz Julio , Casado Araceli , Torres Covadonga 
Published: November 2014

IntroductionTolerability and convenience are crucial aspects for the long‐term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients’ well‐being, assessed by several validated measures.MethodsProspective, multicenter study. Adult HIV‐infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG‐HIV Symptom Index), quality of life (EQ‐5D, EUROQoL & MOS‐HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed.ResultsInterim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co‐infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG‐HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well‐being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001.ConclusionsSwitching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV‐infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.
Switching to lamivudine plus darunavir/r dual therapy in a cohort of treatment‐experienced HIV‐positive patients: the experience of an Italian centre
Authors: Borghetti Alberto , Mondi Annalisa , Piccoli Benedetta , Gagliardini Roberta , Lamonica Silvia , Ciccarelli Nicoletta , D'Avino Alessandro , Pallavicini Federico , Cauda Roberto , De Luca Andrea , Fabbiani Massimiliano , Di Giambenedetto Simona 
Published: November 2014

IntroductionAccording to recent evidence about boosted protease inhibitors (PIs/r)‐simplified regimens, the combination of 3TC and DRV/r 800/100 mg could represent a feasible option for optimizing antiretroviral therapy (ART) in treatment‐experienced HIV+ patients.Patients and MethodsWe retrospectively evaluated patients switching to 3TC+DRV/r, with at least six months of viral suppression, no resistance mutation to DRV or 3TC and not HBV‐coinfected: incidence of ART discontinuation and of virological failure (VF: 2 consecutive HIV‐RNA determinations>49 cps/mL or a single one≥1000 cps/mL) and the probability of remaining discontinuation‐free during one‐year follow‐up (FU), as well as changes in laboratory parameters at 1, 3, 6 and 12 months were estimated.ResultsWe included 94 patients: 74 males, mostly MSM (39.4%), with 49 years old, 9 years of HIV disease, 8 years of ART (median values). Median nadir CD4 count and zenith viral load (log10) were 194 cells/µL and 4.90, respectively. Ten patients were HCV‐coinfected and 38 had at least a previous VF. Seventy‐four patients were on an NRTIs‐based triple regimen (mainly TDF/FTC or 3TC/ABC) whereas 14 on another PI‐based dual therapy (mainly LPV/r). Incidence of treatment discontinuation was 12.4 per 100 patients‐year follow‐up (PYFU), but only 2 patients experienced a VF (3.5 per 100 PYFU). Mean time free from discontinuation was 5 years (95% CI 4–6), with a cumulative one‐year estimated probability of staying on 3TC+DRV/r of 85.9%. At three months, a trend of increased CD4 cells count (+42 cells/µL, p 0.059) was observed, but not confirmed at later time point; an increase of total cholesterol (TC, +17mg/dL, p 0.008) and LDL (+19 mg/dL, p 0.002), and a decreased level of AST and ALT (−2 UI/L, p 0.045; −5 UI/L, p 0.009, respectively) were also detected. Total bilirubin was reduced (−0.71 mg/dL, p 0.038). At 6 and 12 months, alteration of lipid profile was similar, with also an increased TC/HDL ratio (+0.48, p=0.030, at six months) and HDL/LDL ratio (−0.04, p=0.035, at 12 months). A significant decrease in ALT levels (−6 UI/L, 0.013) and a diminishing trend for AST and total bilirubin, as well as a significant increase in renal function (GFR +4mL/min, p 0.048) were observed at 12 months.ConclusionsThese observations on 3TC+DRV/r‐based dual therapy simplification in virologically suppressed patients show a good profile of efficacy and safety. An extended FU time is needed in order to establish the real impact of this promising therapeutic choice.
Safety and therapeutic efficacy of the switch to maraviroc+darunavir/ritonavir in HIV/HCV coinfected patients: initial results from GUSTA study
Authors: Gagliardini Roberta , Rossetti Barbara , Bianco Claudia , Rusconi Stefano , Colafigli Manuela , Prinapori Roberta , Francisci Daniela , Fantauzzi Alessandra , Orofino Giancarlo , Vignale Francesca , Di Giambenedetto Simona , De Luca Andrea 
Published: November 2014

IntroductionHIV/HCV coinfection is a risk factor for hepatic injury in patients receiving HAART and previous studies support a favourable effect of antiretroviral regimens including maraviroc (MVC) on the course of coinfection compared with other antiretroviral drugs. There are few observations about MVC use in simplified treatment of coinfected patients.Objective: To evaluate the efficacy and the safety of simplification to darunavir (DRV)/ritonavir (r)/maraviroc (MVC) in virologically HIV‐suppressed patients and to explore the effect of simplified treatment on coinfected patients.Material and MethodsGUSTA study is a randomized two arms trial that compares the switch to DRV/r/MVC with standard HAART with three drugs. The study enrols patients with HIV‐1 RNA<50cp/mL>6 months, R5 tropism, CD4>200 cells/mm. Survival analysis was used to analyze factors associated to time‐to a single viral load (VL) over 50cp/mL and FIB‐4>1.45.ResultsWe included 62 patients with at least the 24 week follow‐up for FIB‐4 analysis: males 75.8%, heterosexuals 48.4%, HCV+12.9% median age 48.3 years (IQR41.1;53.5), time from HIV diagnosis 11.0 years (IQR7.3;16.7), CD4 cells 659/mm (IQR478;882), nadir CD4 203/mm (IQR115;286), FPR 46 (IQR30;70), baseline (BL) FIB‐4 1.11 (IQR0.75;1.35). At BL no differences were observed in the two arms, except for platelets (−34.96 109/L, in the study arm, p=0.028) and CD4 at nadir (−70cell/µL, p0.051). After 24 weeks a significant reduction in total bilirubin (TB) (−0.55 mg/dL, p=0.025) and alkaline phosphatase(AP) (−12.96 UI/L, p=0.002) was observed in the study group. A statistically significant difference in mean change of TB (0.61 mg/dL, p=0.016) and AP (13.23 UI/L, p=0.04) at 24 week between control and study group was observed. No grade 3/4 transaminase elevation was observed for any patient even if HIV/HCV coinfected and receiving MVC. A single HCV negative patient in the control arm had grade 3 bilirubin increase. Including all patients with at least one follow‐up HCV status was not associated with an increased risk of detectable VL (n=114, 4072 person‐week‐follow‐up [IQR12;51.6]), nor with FIB‐4>1.45 (n=98, 3513 person‐week‐follow‐up [IQR11.4;50.9]).ConclusionsThe initial results from GUSTA study show that ART‐regimen including MVC did not increase the incidence of adverse events or severe laboratory liver abnormalities in HIV‐1‐infected patients with or without HCV coinfection. Coinfected patients did not show an increased risk of failure on simplification treatment with MVC/DRV/r.
DRV concentrations and viral load in CSF in patients on DRV/r 600/100 or 800/100mg once daily plus two NRTI
Authors: Di Yacovo Silvana , Molto Jose , Ferrer Elena , Curran Adrian , Jayne Else Laura , Clotet Bonaventura , Tiraboschi Juan , Niubo Jordi , Vila Antonia , Podzamczer Daniel 
Published: November 2014

IntroductionDarunavir/r (DRV/r) is currently used at a dose of 800/100 mg once daily (OD) in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF) might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV‐1 viral load (VL) in CSF patients receiving DRV 600/100 mg OD.MethodsDRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800) vs 600/100 mg (DRV600) OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011‐006272‐39). Here we present the results of a CSF sub‐study. A lumbar puncture (LP) was performed in participating patients after at least six months of inclusion in the study, 20–28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL) was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS) and in plasma using high‐performance liquid chromatography (HPLC).ResultsSixteen patients were included (eight in each arm). All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range) age was 48 (17–71) years, CD4 cell count 532 cells/mL (190–1,394). Median total time on DRV/r was 30 (11–57) months, and since the beginning of the study 8 (6–12) months in DRV800 and 10 (7–12) months in DRV600 patients. LP was performed a median of 26 (24–28) hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326–3,742) ng/mL, CSF levels 17.08 (5.79–30.19) ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028–0.0388), while in the DRV800 arm, median DRV plasma levels were 1,707 (958–3,910) ng/mL, CSF levels 13.23 (3.47–32.98) ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018–0.0262). All patients had VL<40 copies/mL in plasma and 14 patients VL<40 copies/mL in CSF. Two patients (1 in each arm, and taking TDF/FTC) had detectable VL in CSF (280 and 159 c/mL). These patients had the lowest CSF DRV concentrations (5.47 and 3.47 ng/mL), with plasma DRV concentrations of 802 and 958 ng/mL respectively.ConclusionsCSF DRV concentrations and CSF VL were similar between patients receiving DRV/r 800/100 mg or 600/100 mg OD. Low CSF DRV concentrations might be associated with viral escape in CNS. This may be taken into account in patients receiving OD DRV/r. Larger studies should confirm these findings.
Low level HIV viremia is more frequent under protease‐inhibitor containing firstline therapy than under NNRTI‐regimens
Authors: Wiesmann Frank , Braun Patrick , Knickmann Mechthild , Knechten Heribert 
Published: November 2014

IntroductionAn association of persistent low level viremia (LLV) below 500 copies/mL and a higher risk of therapy failure is still point of controversial discussion. Furthermore, it seems that LLV occurs more frequently in patients with protease‐inhibitor regimens than in NNRTI‐ / or integrase‐inhibitor containing therapies. The focus of this work was to assess the prevalence of LLV (50–200 copies/mL) and weak viremia (201–500 copies/mL) in firstline‐treated patients according to their therapy regimen.MethodsA total of 832 and 944 patients from 23 German centres were under firstline therapy in 2012 and 2013, respectively. All patients received their therapy for more than 24 weeks. VL data was related to clinical data retrospectively including ART‐composition, subdivided into NNRTIs (Efavirenz, Nevirapine), PIs (Atazanavir, Darunavir, Lopinavir) and INIs (Raltegravir). Low viremic patients were classified into two arms of 50–200 copies/mL (group A) and 201–500 copies/mL (group B).ResultsSuccess of therapy was defined as <50 copies/mL and was observed in 90.0% and 91.1% (2012/2013), respectively. An additional 2.0% and 2.3% had LLV. The amount of viremic patients with VLs <500 copies/mL differed significantly between NNRTI‐based firstline regimens 1.7% and 2.5% and PI‐based regimens 4.8% and 5.7% (2012/2013), respectively. LLV was clearly less often observed in EFV‐based‐ (1.6% and 1.1% [group A] / 0.4% and 0.4% [group B]) or NVP‐based firstline therapies (1.0% and 3.6% [group A] + 0% and 0% [group B]) than in ATV‐based‐ (7.5% and 3.8% [group A] + 1.5% and 2.5% [group B]), DRV‐based‐ (2.9% and 3.0% [group A] + 2.2% and 0% [group B]) or LPV‐based firstline therapies (1.6% and 3.3% [group A] + 0.8% and 2.5% [group B]) and also in parts for RAL‐based regimens (0% and 3.7% [group A] + 0% and 1.9% [group B]).ConclusionsLLV is more often observed under PI‐based firstline than under NNRTI‐regimens. Only one NNRTI‐patient of group B remained on therapy. A possible explanation for this discrepancy might be the fact that physicians seem to tolerate LLV more often in PI‐regimens than in NNRTI‐regimens due to a higher genetic barrier against resistance and it remains a point of discussion if constant LLV does affect immune recovery and risk of therapy failure.