bluuebunny/crossref_metadata_2025_split huggingface dataset:
Week 48 results of a Phase IV trial of etravirine with antiretrovirals other than darunavir/ritonavir in HIV‐1‐infected treatment‐experienced adults
Authors: Arathoon Eduardo , Bhorat Asad , Silaghi Rodica , Crauwels Herta , Lavreys Ludo , Tambuyzer Lotke , Vanveggel Simon , Opsomer Magda 
Published: November 2014

IntroductionIn DUET, etravirine (ETR) 200 mg bid had durable efficacy and a favourable safety profile versus placebo, both arms with an optimised background regimen (BR) including darunavir/ritonavir (DRV/r). TMC125IFD3002 (VIOLIN; NCT01422330) investigated ETR plus ARVs other than DRV/r.Materials and MethodsThis was a 48 week, Phase IV, open‐label, single‐arm, multicentre study. HIV‐1‐infected treatment‐experienced adult patients on=8 weeks ARV therapy prior to screening, switching either for virologic failure (VF) (viral load [VL] =500 c/mL) or regimen simplification/AEs (RS/AE) (VL<50 c/mL), received active ETR 200 mg bid with an investigator‐selected BR of =1 active ARVs, but excluding DRV/r or NRTIs only. The primary objective was to evaluate safety, tolerability and pharmacokinetics (PK).ResultsOf 211 treated patients, 55% were female, 61% black/African American. 155 patients (73%) had baseline (BL) VL=50 c/mL versus 56 (27%) with BL VL<50 c/mL. Between these two latter subgroups, median BL VL was 4.42 versus 1.28 log10 c/mL and CD4+ count 238 versus 410.5 cells/mm3. Overall, 96% previously used <2 NNRTIs and 99% used=5 PIs; median number of BL NNRTI RAMs was 2, PI RAMs 5 and NRTI RAMs 1. Overall, most common BR ARVs were PIs (83%), mostly lopinavir/r (62%) and mostly used alone (20%) or with 1 or 2 NRTIs (61%). Raltegravir was used in 9% of patients. Most frequent AEs (any cause/grade) were diarrhoea (17%) and URTI (8%). Incidence of grade 3–4 AEs was 13%, serious AEs 5% (no rashes; none ETR related), AEs leading to discontinuation 4%, AEs possibly related to ETR 23% and AEs of interest: rash (any type) 4%, hepatic 6% and neuropsychiatric 3%. At week 48, VF and RS/AE virologic responses (% patients with VL<50 c/mL; FDA Snapshot) were: 48% (74/155) and 75% (42/56), respectively. VF rates were 42% and 13%; 10% and 13% had no VL data in the week 48 window. The percentage of patients adherent to treatment (assessed based on PK sampling plus ETR pill count) was 47% (69/148) and 57% (30/53), in VF and RS/AE, respectively. Median CD4+ count (NC=F) increases were 0.0 and 24.0 cells/mm3. In 29/49 of VFs with genotypic data at failure, ETR RAMs emerging in =5 patients were Y181C, E138A and M230L. The geometric mean ETR AUC12h was 4877 ng.h/mL and C0h 293 ng/mL (N=199).ConclusionsResults of this study were consistent with those for ETR in other similar populations and support the use of ETR 200 mg bid with a non‐DRV/r based BR.
Antiretroviral therapy (ART) management of Low‐Level Viremia in Taiwan (ALLEVIATE)
Authors: Cheng Chien‐Yu , Luo Yu‐Zhen , Wu Pei‐Ying , Liu Wen‐Chun , Yang Shan‐Ping , Zhang Jun‐Yu , Cheng Shu‐Hsing , Hung Chien‐Ching 
Published: November 2014

IntroductionThis retrospective study aimed to investigate that if switch of combination antiretroviral therapy (cART) would result in viral suppression (<40 copies/mL) at 48 weeks for patients with persistent low‐level viremia after having received cART for six months or more at two hospitals designated for HIV care in Taiwan.Materials and MethodsBetween January 2001 and January 2013, patients were enrolled if plasma HIV RNA load (PVL) were >20 to <1000 copies/mL detected for six months or more [1, 2]. Using a standardized data collection form, we recorded data of PVL and CD4 count before cART and at the detection of low‐level viremia, serologies for hepatitis B and C virus, risk factors, duration of cART exposure, years of HIV diagnosed and ever experiencing treatment failure. The strategy of switch is based on the clinical guidelines of BHIVA, which suggest change of cART from non‐nucleoside reverse‐transcriptase inhibitors (nNRTIs) or unboosted protease inhibitor (PI) to boosted PI, newer boosted PI or ARV of different mechanism [3].ResultsIn this study, 165 patients were enrolled, 119 patients (72.1%) did not switch (Group 1), and 46 patients (27.9%) switched previous regimens to ARV of different mechanism (Group 2). The two groups differed significantly in the proportion of injecting drug users (IDU) (Group 1 vs Group 2, 10.9 vs 26.1%) and median PVL (67 vs 159 copies/mL), and the proportion of PVL<200 copies/mL (84.0% vs 58.7%) when low‐level viremia was first detected. In Group 1, 39 (32.8%) continued two nucleoside reverse‐transcriptase inhibitors (NRTIs) plus nNRTI; 29 (24.4%) 2 NRTIs plus PI, 47 (39.5%) 2 NRTIs plus boosted PI, and 4 (3.3%) 2 NRTIs plus integrase inhibitor (II). In Group 2, two (4.3%) switched to 2 NRTIs plus PI, 38 (82.6%) 2 NRTIs plus boosted PI, three (6.5%) 2 NRTIs plus II and three (6.5%) boosted PI plus II. In multivariate analysis, IDUs (adjusted odds ratio [AOR], 6.757; 95% CI 2.427–18.868) and PVL of 200–999 copies/mL at enrollment (AOR, 4.902; 95% CI 1.992–12.048) were more likely to be switched. At 48 weeks, patients in Group 2 were more likely to achieve PVL<40 copies/mL than Group 1 (82.6% vs 63.0%, p=0.016), while no difference was observed in achieving PVL <200 copies/mL between the two groups (95.7% vs 92.4%, p=0.729).ConclusionsAccording to the clinical guidelines of BHIVA, patients with low‐level viremia who switched to cART consisting of 2 NRTIs plus boosted PI or newer mechanisms were more likely to re‐establish viral suppression to <40 copies/mL at week 48.
Effectiveness and durability of darunavir/ritonavir (DRV/r) in DRV/r‐experienced HIV‐1‐infected patients in routine clinical practice
Authors: Antinori Andrea , Galli Massimo , Gianotti Nicola , Mussini Cristina , Quirino Tiziana , Sterrantino Katia , Mancusi Daniela , Termini Roberta 
Published: November 2014

IntroductionThis was a descriptive non‐interventional study in HIV‐1‐infected patients treated with DRV/r conducted in the clinical setting, with a single‐arm prospective design. The primary objective was to collect data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in the marketing authorization. Efficacy (measured as viral load [VL] <50 copies/mL and CD4+ cell count) was evaluated for DRV/r in combination with other antiretroviral (ARV) agents in routine clinical practice in Italy.Materials and MethodsHere we describe an analysis of effectiveness and durability data from two cohorts of DRV/r‐experienced patients with HIV‐1 infection, already receiving DRV/r according to usual clinical practice, collected prospectively from June 2009 to December 2012: Cohort 1, data from patients from the DRV/r Early Access Program (TMC114‐C226 study; N=235 patients) and Cohort 2, a separate cohort of ARV‐DRV/r‐experienced patients (N=407 patients), treated with DRV/r in the market. Patient characteristics are shown in Table 1.ResultsThe median length of DRV/r exposure during the study was 925 days (interquartile range [IQR] 692–1006) in Cohort 1, and 581 (IQR 508–734) days in Cohort 2. Of those patients that completed the study, 94% and 87% of patients were virologically suppressed in Cohort 1 and 2, respectively, at last study visit (LSV). As expected, the virological suppression rate was higher in patients with baseline VL <50 copies/mL (Table 2). Mean CD4+ cell counts improved from baseline to LSV in both cohorts (Cohort 1: +54 cells/µL [95% CI 31, 77] and Cohort 2: +59 cells/µL [95% CI 44, 73]). High persistence rates were seen in both cohorts, with 75.3% of patients in Cohort 1 and 82.6% in Cohort 2 remaining on treatment at LSV; very few patients discontinued due to virologic failure (Table 1). Other reasons for study discontinuation are shown in Table 1. Very few patients changed DRV/r dosing during the study, 15 from 1200 to 800 mg o.d.ConclusionsIn patients already treated with DRV/r, DRV/r‐based ARV treatment provided effective viral suppression with long‐lasting durability, low virological response failure, low discontinuation rates and good tolerability. These data confirm DRV/r to be an effective treatment choice in previously treated patients.
Switch to raltegravir‐based regimens and HIV DNA decrease in patients with suppressed HIV RNA
Authors: Bianco Claudia , Meini Genny , Rossetti Barbara , Lamonica Silvia , Mondi Annalisa , Belmonti Simone , Fanti Luri , Ciccarelli Nicoletta , Di Giambenedetto Simona , Zazzi Maurizio , De Luca Andrea 
Published: November 2014

IntroductionRaltegravir intensification is associated with an increase in 2‐LTR episomal HIV DNA= circles, indicating a persistent low‐level replication, in some individuals in ART with suppressed HIV RNA. We aimed at monitoring residual plasma HIV RNA and cellular HIV DNA in virologically suppressed patients switching to a raltegravir‐based regimen.Materials and MethodsForty‐six HIV‐infected subjects on PI or NNRTI based‐regimens, with plasma HIV RNA level <40 copies/mL for ≥6 months and CD4 >200 cells/µL for ≥12 months were enrolled. Thirty‐four patients switched to raltegravir‐based regimen (RASTA study group) and 12 continued a PI or NNRTI based‐regimen (control group). Ultrasensitive HIV residual viremia and total PBMC HIV DNA were assessed at baseline (W0), 24 (W24) and 48 (W48) weeks. HIV RNA levels were determined by an ultrasensitive test derived from a commercial real time PCR (limit of detection 5 copies/ml). A real time PCR was used to quantify HIV DNA copy numbers in PBMCs.ResultsAt W0, HIV DNA was detected in all patients while at W48 it was detectable in 82.3% of RASTA group vs 100% of controls (p=0.01). The difference between the average values of HIV DNA log10 copies/10°6 CD4 at W0 (median 3.11, IQR 2.70–3.45) and W48 (median 2.87, IQR 2.24–3.38) was statistically significant for RASTA group (p=0.035). Male gender (mean difference −0.37 log10 copies/10°6 PBMC, p=0.023) and previous PI based‐ART (mean difference +0.39 log10 copies/10°6 PBMC, p=0.036) were predictive of HIV DNA level at W0. After adjusting for previous PI based‐ART, male gender was the only variable independently associated with HIV DNA size at W0 (mean difference −0.326 log10 copies/10°6 PBMC, 95% CI −0.641, −0.011 p=0.043). Ultrasensitive HIV‐1 RNA was detectable at W0 in 50% of RASTA group versus 66.7% of controls and at W48 in 32.4% versus 45.5%, respectively. No differences were found between HIV RNA levels at W0 and W48 within and between the two groups.ConclusionsSwitching to raltegravir‐based regimens may be associated with a decrease of HIV reservoir, as measured by total PBMC HIV DNA. A larger sample size is required to confirm this finding.
Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line regimen in an urban clinic in Kampala
Authors: Laker Eva , Mambule Ivan , Nalwanga Damalie , Musaazi Joseph , Kiragga Agnes , Parkes‐Ratanshi Rosalind 
Published: November 2014

IntroductionIn 2011 Uganda recommended boosted atazanavir (ATV/r) as the preferred PI for second line due to once daily dosing, replacing aluvia (LPV/r) [1, 2]. The evidence was based on the BMS O45 trial, of LPV/r vs ATV/r was performed in a high‐income setting, on patients with prior PI use and resistance testing [2, 3]. There are no RCTs or observational studies comparing use of ATV/r with LPV/r in patients failing NNRTI first line antiretroviral therapy in sub‐Saharan Africa [3, 4]. The Infectious Diseases Institute (IDI) has a large second line cohort (>1838). This aims to compare clinical, immunologic and virologic response of LPV/r versus ATV/r at IDI.MethodsRetrospective cohort analysis on routinely collected data of patients switched to second line with NRTI backbones TDF/3TC or FTC, AZT/3TC, ABC/3TC from January 2009 to December 2013. Students T‐tests and Chi‐square tests were used in this analysis.ResultsA total of 1286 (73.5% female) patients were switched to LPV/r 991 (77%) and ATV/r 295 (23%) (p<0.001). NRTI backbones were 760 on TDF/3TC (66.8% LPV/r vs 33.2% on ATV/r), 504 on AZT/3TC (93.3% vs 6.7%), and 22 on ABC/3TC (59% vs 41%). Median (IQR) time on first line for LPV/r was 21 (1–44) months and for ATV/r was 41 months (22–68). Median CD4 (IQR) at switch to LPV/r was 181 cells/uL (66–424) and to ATV/r was 122 (57–238) (p≤0.001). A total of 366 patients had CD4 done at six months after switch and the mean (IQR) CD4 increase was 153 (54–241) for LPV/r versus 116 (52–171) for ATV/r (p=0.232). Additionally, 304 had a CD4 at 12 months and the means were 172 (45–272) for LPV/r vs 179 (60–271) for ATV/r (p=0.426). There was no significant difference in the mean increment by NRTI backbone or by stratifying to viral load (VL) at time of switch to VL <100,000 and ≥100,000. Median (IQR) VL at switch was 61,000 (13,000–2,030,000) LPV/r and 51,000 (14,000_151,000) ATV/r. 269 had a VL done in the first 12 months and 178/250 (71.2%) on LPV/r versus 16/19 (84.2%) on ATV/r were undetectable (p=0.228). 259 (26%) LPV/r versus 33(11%) ATV/r had ≥1 opportunistic infections on second line (p<0.001).ConclusionsThis is an observational study based on our experience at IDI. Like elsewhere in Africa, there is no routine viral load testing, making it difficult to get sensitive analysis of data on ART efficacy within routine clinical practice. Nevertheless, this observational study is reassuring in terms of efficacy of both ATV/r and LPV/r for patients failing first line therapy in our setting.
Switching to nevirapine‐based regimens after undetectable viral load is not associated with increased risk of discontinuation due to toxicity
Authors: Patterson Patricia , Socías Eugenia , Pryluka Daniel , Lapadula Pablo , Pérez Héctor , Cahn Pedro 
Published: November 2014

IntroductionDue to its good tolerability, favourable cardiovascular risk‐profile, low‐pill burden and cost, nevirapine‐based regimens are an attractive simplification strategy for patients with suppressed viral load (VL). However, current guidelines recommend caution if nevirapine (NVP) is prescribed in males and females with CD4 counts above 400 or 250 cells/µL, respectively. The aim of this study is to determine the prevalence and risk factors associated with development of toxicity or treatment discontinuation in patients switching to NVP‐based regimens.Materials and MethodsRetrospective chart review of HIV‐infected patients with suppressed VL who switched from a PI‐based regimen to a NVP‐based regimen in four HIV clinics in Argentina, between 1997 and 2013. Bivariate and multivariate analyses were performed to explore factors associated with treatment discontinuation. High CD4 count was defined as CD4‐cell count ≥400 or 250 cells/µL in males and females, respectively.ResultsOf 218 patients included, 165 (75.7%) were male; 21 (9.6%) were co‐infected with HCV and/or HBV. Median baseline (BSL) CD4 count: 138 cells/µL (IQR: 64–276). At switch, patients had a median age of 38 years (IQR: 33.4–43.8) and had been suppressed for a median of 1.4 years (IQR: 0.6–2.2); 138 patients (63.3%) had high CD4‐cell counts: among females, median CD4 count at switch was 462 (IQR: 330–709) cells/µL; among males, 433 (IQR: 305–595) cells/µL. Thirty‐six patients (13.5%) presented NVP‐related toxicity (30 skin toxicity, 6 hepatic toxicity), 29 (13.3%) discontinued NVP. Median time to development to toxicity: 32 days (IQR: 15–75). In bivariate analysis, chronic hepatitis was the only variable associated with development of toxicity (OR: 2.90, 95% CI 1.08–7.78). In multivariate analysis, no statistical significant associations were observed between either development of toxicity or treatment discontinuation and gender, chronic hepatitis, age or CD4‐cell count at BSL or at switch (all p>0.05).ConclusionsIn our study, switching to a NVP‐based regimen in patients with undetectable VL was associated with a low incidence of skin or liver toxicity, and treatment discontinuation. Moreover, these were unrelated to the CD4‐cell count. Our findings suggest that, in contrast with ART‐naïve patients, switching to NVP‐based regimens could be a safe strategy for patients with suppressed viremia regardless of the CD4‐cell count.
Lipid changes in HIV‐patients switching to the coformulated single tablet FTC/RPV/TDF (Eviplera®). Efficacy and safety analysis. GeSida Study 8114
Authors: Pérez‐Hernández Isabel A , Palacios Rosario , Mayorga Marisa , González‐Doménech Carmen M , Castaño Manuel , Rivero Antonio , del Arco Alfonso , Lozano Fernando , Santos Jesús 
Published: November 2014

IntroductionRilpivirine (RPV) has a better lipid profile than efavirenz (EFV) in naïve patients [1]. Switching to RPV may be convenient for many patients, while maintaining a good immunovirological control [2]. The aim of this study was to analyze lipid changes in HIV‐patients at 24 weeks after switching to Eviplera® (emtricitabine/RPV/tenofovir disoproxil fumarate [FTC/RPV/TDF]).Materials and MethodsRetrospective, multicentre study of a cohort of asymptomatic HIV‐patients who switched from a regimen based on 2 nucleoside reverse transcriptase inhibitors (NRTI)+protease inhibitor (PI)/non nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir boosted PI monotherapy to Eviplera® during February‐December, 2013; all had undetectable HIV viral load for ≥3 months prior to switching. Patients with previous failures on antiretroviral therapy (ART) including TDF and/or FTC/3TC, with genotype tests showing resistance to components of Eviplera®, or who had changed the third drug of the ART during the study period were excluded. Changes in lipid profile and cardiovascular risk (CVR), and efficacy and safety at 24 weeks were analyzed.ResultsAmong 305 patients included in the study, 298 were analyzed (7 cases were excluded due to lack of data). Men 81.2%, mean age 44.5 years, 75.8% of HIV sexually transmitted. 233 (78.2%) patients switched from a regimen based on 2 NRTI+NNRTI (90.5% EFV/FTC/TDF). The most frequent reasons for switching were central nervous system (CNS) adverse events (31.0%), convenience (27.6%) and metabolic disorders (23.2%). At this time, 293 patients have reached 24 weeks: 281 (95.9%) have continued Eviplera®, 6 stopped it (3 adverse events, 2 virologic failures, 1 discontinuation) and 6 have been lost to follow up. Lipid profiles of 283 cases were available at 24 weeks and mean (mg/dL) baseline vs 24 weeks are: total cholesterol (193 vs 169; p=0.0001), HDL‐c (49 vs 45; p=0.0001), LDL‐c (114 vs 103; p=0.001), tryglycerides (158 vs 115; p=0.0001), total cholesterol to HDL‐c ratio (4.2 vs 4.1; p=0.3). CVR decreased (8.7 vs 7.5%; p= 0.0001). CD4 counts were similar to baseline (653 vs 674 cells/µL; p=0.08), and 274 (96.8%) patients maintained viral suppression.ConclusionsAt 24 weeks after switching to Eviplera®, lipid profile and CVR improved while maintaining a good immunovirological control. Most subjects switched to Eviplera® from a regimen based on NNRTI, mainly EFV/FTC/TDF. CNS adverse events, convenience and metabolic disorders were the most frequent reasons for switching.
Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter analysis
Authors: Zaccarelli Mauro , Fabbiani Massimiliano , Pinnetti Carmela , Borghi Vanni , Giannetti Alberto , Sterrantino Gaetana , Lorenzini Patrizia , Latini Alessandra , Loiacono Laura , Colafigli Manuela , Ammassari Adriana , D'Ettorre Gabriella , Plazzi Maddalena , Di Giambenedetto Simona , Antinori Andrea 
Published: November 2014

BackgroundTo assess the role of drugs used in dual therapy (DT), as cART simplification, over the risk of treatment failure.Materials and MethodsPatients starting DT regimen composed by a boosted protease inhibitor (PI/r): darunavir (DRV/r), lopinavir (LPVr) or atazanavir (ATV/r) plus a second drug: raltegravir (RAL), maraviroc (MRV) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF), this one generally used in HBV co‐infected patients, were included. The effect of each drug as well as other clinical and virological cofactors over treatment failure was assessed using survival analysis.ResultsOverall, 480 patients from six reference Italian centres were included: all switched to DT with HIV‐RNA <500 cp/µL, 376 of them at <50 cp/µL. Patients who switched at <50 cp/µL showed a significant lower risk of treatment failure (13.3% versus 23.3% at 1 year and 28.0% versus 44.6% at 3 years, p=0.005), thus the analysis was focused on this subgroup. Among the patients who switched at <50 cp/µL, the proportion of drug used in DT was: DRV/r 63.0%, RAL 53.7%, ETR 19.4%, ATV/r 18.4%, MRV 17.3%, LPV/r 12.8%, TDF 6.4% and 3TC 5.9%; DRV/r‐RAL was the most widely used combination: 32.5%. Treatment failure was observed in 78 patients, of whom 38 virological and 35 for toxicity/intolerance, one patient died during follow‐up and four patients interrupted for personal decision with undetectable HIV‐RNA. At Cox Model, adjusted by gender, age, non‐Italian origin, AIDS diagnosis, time on cART, number of regimens, CD4 nadir, baseline CD4, all the drugs had a positive effect on probability of failure (Figure), however the effect was significant for DRV/r (HR:0.21, 95% CI 0.07–0.59, p=0.03), ATV/r (0.30, 0.09–0.97, p=0.044) and RAL (0.37, 0.15–0.93, p=0.034); higher CD4 count at baseline was also associated with lower risk of failure while number of previous regimens with a higher risk. Moreover, ATV/r was found significant associated with significant higher risk of failure by toxicity (as well as LPV/r) but lower risk of virological failure, while both 3TC and RAL with significant lower risk of toxicity.ConclusionsOur analysis suggest that using PI/r‐based DL is highly effective if switching from HIV‐RNA <50 cp/µL; DL should be used with caution in patients with low CD4 count and longer history of treatment; DRV/r is the best compromise among PI/r, ATV/r is effective but is associate with frequent interruption by toxicity; RAL showed high tolerability so that its use is related to the lowest risk of failure as second drug.