bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of a dual therapy based on darunavir/ritonavir and etravirine in ART‐experienced patients
Authors: Ignacio Bernardino Jose , Xavier Zamora Francisco , Valencia Eulalia , Moreno Victoria , Vergas Jorge , Jesus Tellez Maria , Estrada Vicente , Gonzalez‐Garcia Juan 
Published: November 2014

IntroductionNucleoside reverse transcriptase inhibitors (NRTI)‐sparing regimens have been studied in antiretroviral therapy (ART)‐naïve patients but data with ART‐experienced are scarce. NRTI‐sparing regimens may be an option in patients with toxicities and for simplification reasons.MethodsRetrospective multicentre analysis including ART‐experienced patients starting treatment with darunavir/ritonavir and etravirine (DRV/r 800 mg/100 mg QD or 600 mg/100 mg BID and ETV 400 mg QD or 200 mg BID) with at least six months of follow‐up. Primary endpoint was proportion of patients with VL<50 copies/mL at 48 weeks with an ITT analysis (missing or switch equals failure). Secondary endpoints were safety, CD4 count and lipid changes over 48 weeks.ResultsSeventy‐five patients were included of whom 44 (58.6%) had HIV RNA<50 copies/mL. Baseline characteristics: median age 50 years (IQR 34–65), 72% males, 93% Caucasians, 38.6% hepatitis C, and 45.4% with CDC C stage. Median HIV duration and time on ART were 20 (IQR 7–28) and 14 years (IQR 5–21) respectively. Reasons for switching were virologic failure in 27 (36%), simplification in 25 (33.3%), toxicity in 20 (26.6%) and other 3 (4.1%). Most of them received DRV/r and ETV QD. Thirty‐nine patients had NNRTI resistance mutations [28 K103N (37.3%), 6 Y181I/C (8%), 3 G190A (4%)] and 29 patients had ≥1 primary PI mutations. Main analysis (ITT) showed that 67 (89.3%) had a VL undetectable at 24 weeks (95% CI 83.1–95.5) and 57 (76%) at 48 weeks (95% CI 68.4–83.6). On treatment analysis showed that 94.3% and 89% had a viral load<50 copies at 24 and 48 weeks, respectively. 11 (14.6%) patients discontinued the regimen (three virologic failures, three switching to darunavir/ritonavir monotherapy, two to salvage regimen and three due to toxicity). No significant changes in CD4+ count and lipid changes were observed at 48 weeks.ConclusionsDual therapy with Darunavir/ritonavir and etravirine is an efficacious and safety option in ART‐experienced HIV patients even in patients on virologic failure.
The efficacy, pharmacokinetics, safety and cardiovascular risks of switching nevirapine to rilpivirine in HIV‐1 patients: the RPV switch study
Authors: Rokx Casper , Blonk Maren , Verbon Annelies , Burger David , JA Rijnders Bart 
Published: November 2014

IntroductionNevirapine (NVP) induces cytochrome P450 3A4 by which rilpivirine (RPV) is metabolized. Switching NVP to RPV could result in decreased RPV exposure with subsequent virological failure and dyslipidemia because NVP is regarded as the least dyslipidemic, non‐nucleoside, reverse transcriptase inhibitor. This trial evaluated the efficacy, pharmacokinetics, safety and cardiovascular risks of switching NVP to RPV.Materials and MethodsProspective open label controlled trial. HIV‐1 patients with HIV‐1 RNA <50 copies/mL on once daily NVP, emtricitabine/tenofovir (FTC/TDF) switched to single tablet RPV/FTC/TDF. Eligible patients on NVP, FTC/TDF were controls. Primary endpoint was week 12 HIV‐1 RNA <50 copies/mL by intention to treat analysis. Secondary endpoints were week 24 HIV‐1 RNA <50 copies/mL, NVP and RPV pharmacokinetics, safety and fasting lipids, Framingham risk scores (FRS) and Adult Treatment Panel III (ATP‐III) lipid goals.ResultsOf 189 eligible patients, we included 50 RPV switchers and 139 NVP controls. Week 12 HIV‐RNA was <50 copies/mL in 46/50 switchers (92.0%) which was not different from the hypothesized 90% week 12 suppression rate (p=.431). Forty‐four of 50 switchers had week 24 HIV‐1 RNA <50 copies/mL compared to 126/139 controls (difference: 2.6%, 95% CI −7.6% to 12.8%, p=.593). NVP plasma concentrations were below detection level in all at week 3. Mean week 1 RPV trough concentration was 0.083 mg/L and comparable to phase III trial data (p=0.747). Adverse events occurred in 36 switchers, the majority (82.0%) were grade one. Two switchers discontinued RPV for side effects. Significant changes over 24 weeks (p<0.001) were observed in switchers on total cholesterol (TC, −0.67 mmol/L, 95% CI −0.50 to 0.83), low density lipoprotein (LDL)‐C (−0.36, 95% CI −0.21 to −0.51) and high density lipoprotein (HDL)‐C (−0.28, 95% CI −0.20 to −0.35). The TC/HDL‐C ratio increased 0.20 (95% CI 0.02 to 0.37; p=.029) and systolic blood pressure decreased 6.0 mmHg (95% CI −1.7 to −10.3; p=.007). The median FRS did not change over 24 weeks (8.4% vs. 7.7%; p=.119). More patients achieved LDL‐C (+15%; p=.016) and TC (+25%; p<0.001) ATP‐III treatment goals at week 24 on RPV.ConclusionsA NVP to RPV switch does not influence RPV exposure and results in adequate ongoing HIV‐1 suppression. RPV could be an option for patients at risk for cardiovascular diseases.
Switch to Stribild versus continuation of NVP or RPV with FTC and TDF in virologically suppressed HIV adults: a STRATEGY‐NNRTI subgroup analysis
Authors: Stellbrink Hans‐Juergen , Antinori Andrea , Pozniak Anton , Flamm Jason , Bredeek Fritz , Patel Kiran , Garner Will , Piontkowsky David 
Published: November 2014

IntroductionSwitch to Stribild (STB) was non‐inferior to continuation of a non‐nucleoside reverse transcriptase inhibitor (NNRTI) with emtricitabine and tenofovir DF (FTC/TDF) at week 48 in virologically suppressed HIV adults [1]. We report the Week 48 efficacy and safety of STB versus nevirapine (NVP) or rilpivirine (RPV) with FTC/TDF in suppressed subjects.Materials and MethodsVirologically suppressed subjects on an NNRTI with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB versus continue their NNRTI 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 Week 48 by FDA snapshot algorithm (12% non‐inferiority margin). Subgroup analysis by non‐EFV NNRTI use (NVP [74]; RPV [19]; etravirine [3]) at screening was pre‐specified.ResultsThe mITT population included 433 subjects who were randomized and treated. In the non‐EFV NNRTI subgroup, 59 switched to STB; 37 continued a non‐EFV NNRTI (27 NVP, 10 RPV) with FTC/TDF. At week 48, 97% STB versus 95% non‐EFV NNRTI maintained HIV‐1 RNA <50 c/mL. No emergent resistance was detected in either group. No difference in median increases from baseline in CD4 count at week 48 (cells/µL): 25 STB versus 55 non‐EFV NNRTI (p=0.78). No discontinuation due to adverse events; no cases of proximal renal tubulopathy. As expected, there were no significant changes in the frequency of neuropsychiatric symptoms (i.e. anxiety, insomnia, dizziness, vivid dreams, weird/intense dreams, and nightmares) reported on the HIV Symptom Index at week 48 compared to baseline after switching to STB. There was a greater but non‐progressive decrease from baseline in eGFR in the STB versus non‐EFV NNRTI group; median changes (mL/min) at week 48: −9.1 versus −1.4. Switch to STB was associated with a higher treatment ease (convenience, flexibility, demand, lifestyle, understanding) score (range: −15 to 15) at week 4 (median: 14 vs 11; p=0.047) and week 24 (median: 14 vs 12.5; p=0.038).ConclusionsIn this small group of virologically suppressed subjects, switch to STB vs continuation of NVP or RPV 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.
Use of maraviroc in patients with undetectable viral load: efficacy, tolerance and predictors of viral response in MARAVIROC‐cohort study
Authors: Jesús Pérez Elías María , Arroyo David , Diaz Alberto , Herrero Cristina , Martinez‐Dueñas Loreto , Moreno Ana , Hernández‐Quero Jose , Podzamcer Daniel , Gomez‐Ayerbe Cristina , Luis Casado Jose , Zamora Javier , Rivero Antonio , Moreno Santiago , María Llibre Josep 
Published: November 2014

IntroductionNo controlled clinical trials had studied the role of maraviroc (MRV) in fully suppressed patients [1].Materials and MethodsMRV‐cohort is an observational, retrospective, multicentric (27 sites) large cohort study of patients starting MRV in clinical practice under different circumstances, with at least 48 weeks of follow‐up. For the present analysis we selected all those patients starting with an HIV‐RNA<50 copies/mL. Demographics, baseline CD4 cell count, past history of antiretroviral treatment (ART), tropism, reasons for MRV use, MRV based therapy and change/end of MRV use were assessed. Paired analysis of lipid, hepatic and kidney profile changes and univariate and multivariate analyses of HIV‐RNA<50 copies/mL at 48 weeks were explored.ResultsWe included 247 out of 667 subjects from the entire cohort. At study entry, their median age was 47 years, 23% were women, 31% MSM, 49% had CDC category C, median CD4+ counts were 468 cells/mm3, 46% were HCV+ and 4.5% AgHBs+. Tropism information was available in 197 (94% R5). Median length of prior ARTV was 10.7 years, with exposure to a median of three drug families. Main reasons for prescribing MRV were: toxicity 38%, inmunodiscordance 23%, simplification 19% and admission in a clinical trial 10.4%. MRV based therapies used were MRV+2NRTIs 9%, MRV+PI 46%, MRV+PI+other 40% and MRV+other 5%. At 48 weeks, 23% of patients had changed or finished MRV therapy due to toxicity 2.4%, virological failure 2%, immunological failure 1.2%, simplification 3,2%, trial requirement 9.7%, medical decision 2.8%, treatment suspension 1.2% and unknown 0.4%. At 48 weeks, no significant changes were observed in lipid, hepatic or kidney profiles, and 85% of patients remained with HIV‐RNA<50 copies/mL. Focusing on viral response univariate and multivariate models did not show any significant baseline variable explaining viral failure.ConclusionsIn clinical practice MRV was used, mostly in R5 positive patients, with adequate efficacy and tolerance, but important number of patients changed due to non‐clinical reasons. In this scenario neither reason for use of MRV nor MRV‐based therapy explained viral failure.
Dual therapy with darunavir/r plus etravirine is safe and effective as switching therapy in antiretroviral experienced HIV‐patients. The BITER Study
Authors: Portilla Joaquín , Arazo Piedad , Crusells Josefa , Pérez‐Martínez Laura , Martínez‐Madrid Onofre , Boix Vicente , Moreno Javier , Navarro Vicente , Rubio Teresa , Reus Sergio , Galera Carlos , Bernal Enrique , Jover Francisco , Amador Concepcion , Baño David , Merino Esperanza , Saiz‐de‐la‐Hoya Pablo 
Published: November 2014

IntroductionSwitching therapy studies are usually designed as second‐line antiretroviral treatment (ART) in patients without previous virologic failures. Combined ART (cART) with DRV/r and ETR has a good pharmacokinetic profile, high genetic barrier and has been proved as rescue therapy. The aim of our study was to analyze efficacy and safety of therapy with DRV/r plus ETR in treatment experienced HIV‐patients with previous therapeutic failures that need to switch ART. We present results at first 24 weeks.MethodsMulticentre retrospective observational study. Inclusion criteria: adult HIV‐patients on ART with HIV‐VL <1000 cop/mL who started their ART with DRV/r (600/100 bid or 800/100 qd)+ETR by adverse events, non‐adherence, tolerability or prevention of future complications. Patients with acute AIDS events, HBV, pregnancy, drug addiction or previous selected mutations to DRV or ETR were excluded.ResultsNinety‐nine patients were included, mean age: 47 years (r: 22–79); 70% men, 40.4% previous AIDS event and 39.3% HCV. Ninety‐one patients had received ≥3 cART regimens and 45≥5, 75 patients had HIV‐VL <50 cop/mL and 24 low‐level viremia (LLV): 297.5±261.4 cop/mL, CD4+ 568±279 cells/µL. ART before switching: NRTI+PI/r (33%), NNRTI (17%), PI/r+NNRTI (23%), PI/r+INI (13%), other (14%). Main reason to switching was: toxicity/intolerance 50 patients (renal 32%, gastrointestinal: 14%, hyperlipidaemia 10%; osteopenia/osteoporosis: 6%); improving adherence 26 patients; prevention of complications 19 patients. Nine subjects withdrew ART during follow‐up because: intolerance or new toxicity three; non‐adherence two; simplification to DRV/r monotherapy two; persistence of previous toxicity one; virologic failure one. At week 24, among patients who continued with DRV/r+ETR (n=90): 81 (89%) had VL<50 cop/mL, in those with with HIV‐VL<50 at baseline (67/90), 94% persisted with <50 cop., and in those with LLV (24/90), 61% (n=14) achieved a VL<50 cop. We didn't observe any significant difference in lab parameters between baseline and week 24. Estimated glomerular filtrate rate increased from 83.4±24.7 to 88.5±56.8 mL/min, p=NS. Regarding reason to switching, it improved in 42 cases, no changes: 20 cases; worsened: 4 cases, and non‐applicable or unknown: 24 cases.ConclusionsSwitching to dual therapy with DRV/r+ETR is an effective strategy in selected heavily experienced ART patients, even in those with LLV (<1000 cop/mL). This cART is safe and well tolerated, can reduce number of pills and improve adherence.
Randomized trial of DRV/r or LPV/r QD monotherapy vs maintaining a PI/r‐based antiretroviral regimen in persons with suppressed HIV replication
Authors: Pinnetti Carmela , Lorenzini Patrizia , Cozzi‐Lepri Alessandro , Sandrine Ottou , Tommasi Chiara , Zaccarelli Mauro , Federico Perno Carlo , Rosaria Capobianchi Maria , Girardi Enrico , Antinori Andrea , Ammassari Adriana 
Published: November 2014

IntroductionPI/r monotherapy has been suggested as an attainable maintenance strategy in patients achieving stable HIV suppression in plasma. The objective of trial was to compare the virological outcome of two different PI/r QD monotherapy strategies (LPV/r or DRV/r) with maintaining a triple PI/r‐based ARV regimen.Material and MethodsPhase III, open‐label, non‐inferiority (−12% margin), randomized trial of HIV adults with HIV‐RNA <50 cp/mL for at least 48 weeks while on PI/r‐based cART, CD4 nadir >100 cell/mm3, without previous PIs virological failure. Eligible patients were randomized to continue PI/r+2NRTIs (Arm A), to switch to LPV/r 800/200 mg QD monotherapy (Arm B), or to switch to DRV/r 800/100 mg QD monotherapy (Arm C). Primary endpoint was proportion of patients with plasma HIV‐1 RNA <50 cp/mL (TLOVR) at 48w by intent to treat (ITT) analysis (missing/re‐induction=failure). FDA snapshot and ITT switch‐included analysis (ITT‐SI) were also used. In ITT‐SI, patients who had <50 copies/mL at 96w were counted as successes even if they had confirmed HIV‐RNA elevations and had subsequently successfully intensified by NRTI.ResultsDue to slow recruitment, only 103 patients were included. No differences were observed between the three arms with respect to gender, age, HIV transmission, CD4 nadir and at screening. At randomization, 61 patients were receiving TDF/FTC (60%), 19 ZDV/3TC (18%), 8 ABV/3TC (8%), 75 LPV/r (73%), 13 ATV/r (13%), 4 DRV/r (4%). Differences in proportion of virological success by groups using Arm A as comparator according to FDA TLOVR were reported in Figure 1. Similar results were obtained by Snapshot analysis. Of 14 patients with virological failure, 8 patients restarted triple therapy with 2NRTI and 7/8 regained a VL <50 cp/mL over time. According to ITT‐SI analysis, 96 week differences [95% CI] were −5.7 [−29.6; +18.2] in Arm B, and +19.6 [−1.6; +40.8] in Arm C. A GRT was performed in 6/14 patients (one not amplifiable; four without mutations; one showed E138A).ConclusionsCompared to maintaining a PI/r‐based triple ARV regimen, LPV/r QD monotherapy tended to have higher rate of virological failure and of discontinuation due to adverse event. In contrast, the response rate at week 96 during DRV/r QD mono‐therapy was non‐inferior to that of triple PI/r‐based ARV therapy. A re‐induction with 2NRTI was adequate to obtain an undetectable viremia in most of patients with virological failure.
Unboosted atazanavir with lamivudine/emtricitabine for patients with long‐lasting virological suppression
Authors: Carbone Alessia , Galli Laura , Bigoloni Alba , Bossolasco Simona , Guffanti Monica , Maillard Miriam , Carini Elisabetta , Salpietro Stefania , Spagnuolo Vincenzo , Gianotti Nicola , Lazzarin Adriano , Castagna Antonella 
Published: November 2014

IntroductionUnboosted atazanavir (ATV) including regimens have been investigated as a ritonavir‐sparing simplification strategy. No data are available on removal of one NRTI in subjects effectively treated with unboosted atazanavir+2NRTIs. We present the 48‐week virological efficacy and safety of unboosted atazanavir plus lamivudine (3TC) or emtricitabine (FTC) (lamivudine/emtricitabine/Reyataz©, LAREY Study).Materials and MethodsSingle arm, prospective, pilot study on HIV‐treated patients, HBsAg negative, with HIV‐RNA<50 cps/mL since at least 2 years, who switched from ATV+2NRTIs to ATV 400 mg QD +3TC or FTC. Virological failure was defined as 2 consecutive values of HIV‐RNA>50 cps/ml; viral blip was defined as a single HIV‐RNA value>50 cps/ml not subsequently confirmed. Results as median (IQR). Changes between baseline (BL) and week 48 assessed by the Wilcoxon signed rank test.ResultsForty patients enrolled: 75% males, 51 (47–54) years, 14% HCV co‐infected, infected with HIV since 16 (9–21) years, on antiretroviral therapy since 13 (5–16) years, with a nadir CD4+ of 254 (157–307) cells/mm3, virologically suppressed since 4.2 (2.2–5.4) years; 53 patients switched from a tenofovir (TDF)‐based regimens; ATV was associated with 3TC in 83% patients. No virological failures or discontinuations were observed; three patients had a single viral blip in the range 50–250 copies/mL; CD4+ increased from 610 (518–829) cells/mm3 at BL to 697 (579–858) cells/mm3 at week 48 [48‐week change: 39 (−63/+160) cells/mm3 p=0.081]. Three clinical events were observed (one herpes zoster, one pneumonia, one syphilis) in absence of renal lithiasis, AIDS‐defining or drug‐related events or death. Overall, significant 48‐week amelioration of ALP [BL: 83 (71–107) mg/dL; 48‐week change: −15 (−27/−8) mg/dL p<0.0001] and CKD‐EPI [BL: 100 (86–108) ml/min/1.73 m2; 48‐week change: 1.5 (−3/+8) ml/min/1.73 m2, p=0.042] were observed. Patients switching from TDF (Table 1) significantly improved CD4+, lymphocytes, hepatic profile, renal profile and ALP; these patients had also a modest but significant decrease in haemoglobin.ConclusionsSwitch from an unboosted atazanavir‐based regimen to ATV+3TC or FTC regimen was effective and safe in this small sample, supporting the hypothesis of a potential two‐steps de‐intensification (removal of ritonavir and removal of one NRTI) in patients on long‐lasting virological suppression.
Simplification to co‐formulated rilpivirine/emtricitabine/tenofovir in virologically suppressed patients: Data from a multicenter cohort
Authors: Pinnetti Carmela , Di Giambenedetto Simona , Maggiolo Franco , Lorenzini Patrizia , Fabbiani Massimiliano , Tommasi Chiara , Latini Alessandra , Ammassari Adriana , Loiacono Laura , Sterrantino Gaetana , Bellagamba Rita , Boumis Evangelo , Antinori Andrea , Zaccarelli Mauro 
Published: November 2014

BackgroundTo assess efficacy and safety of treatment simplification to co‐formulated Rilpivirine/Emtricitabine/Tenofovir (RPV/FTC/TDF) in virologically suppressed patients.Materials and MethodsEndpoints of the analysis were: (a) treatment discontinuation of RPV/FTC/TDF for any reasons and (b) occurrence of virological failure (VF) defined as confirmed HIV‐RNA >50 cp/mL).ResultsOverall, 508 patients from five Italian reference centres were included: male gender 71.9%; median age 47 years (IQR 40–52); IVDU as HIV risk 17.7%; HCV‐AB positive 23.4%; CDC‐C stage 17.5%; median CD4 cells/µL at switch 655 (IQR: 487–843); median number of previous regimens three (IQR 2–7). In a median follow‐up of 196 days (IQR: 84–287), 31 patients discontinued RPV/FTC/TDF (virological failure n=5, hypersensitivity reaction n=2, GI‐toxicity n=6, liver toxicity n=1, CNS‐toxicity n=4, kidney toxicity n=5, patient's decision/lost in follow‐up n=10). Moreover, VF occurred in eight patients (five discontinued regimen, while three remained on RPV/FTC/TDF). At survival analysis, the probabilities of treatment discontinuation or VF were 5.5% and 1.2% at 6 months, 13.2% and 2.8% at 12 months, respectively (Figure 1). At adjusted Cox model, factors associated with discontinuation were: <200 CD4 cells/µL at switch (HR 5.3, 95% CI 1.1–25.9, p=0.038), number of pre‐switch regimens (for each extra regimen: HR 1.05, 95% CI 1.01–1.10, p=0.024), male gender (HR 0.4, 95% CI 0.2–0.9, p=0.032). Only the number of pre‐switch regimens was associated with VF (HR 1.13, 95% CI 1.06–1.21, p=0.001). Type of pre‐switch regimen was not associated with discontinuation or failure, but no VF was observed if switching from co‐formulated Efavirenz/FTC/TDF or from Raltegravir containing regimens. Switching to RPV/FTC/TDF led to significant improvement in fasting lipids levels: the decrease in cholesterol, LDL and triglycerides was observed switching from any regimen, but was more marked from boosted PI. In contrast, a moderate increase in transaminase (switching from all regimens except NNRTI‐containing) and creatinine (except from TDF‐containing regimens) were observed.ConclusionsOur data suggest that switching to RPV/FTC/TDF in virologically suppressed patients could be a good strategy with low risk of virological failure or treatment discontinuation; the switch is also associated with significant improvement in lipid profile.