bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly Active Antiretroviral Therapy: Physician Experience and Enhanced Adherence to Prescription Refill
Authors: Delgado Juan , Heath Katherine V , Yip Benita , Marion Stephen , Alfonso Victoria , Montaner Julio SG , O'Shaughnessy Michael V , Hogg Robert S 
Published: April 2022

Objective To identify patient and physician characteristics that may act as determinants of adherence to prescription refill of triple combination antiretroviral therapy. Methods A population-based analysis of antiretroviral therapy-naive HIV-positive men and women in British Columbia, Canada, who initiated triple combination therapy between August 1 1996 and October 31 1998. Study participants were considered adherent if they were actually dispensed antiretrovirals ≥95% over the first year of therapy. Log-binomial regression was used to identify patient and physician characteristics associated with adherence to prescription refill. Results Of the 886 individuals eligible for analysis, 495 (56%) were ≥95% adherent to prescription refill. In multivariate analysis, adherence was positively associated with increased age [adjusted relative rate (ARR) 1.19; 95% CI: 1.07–1.32], having a diagnosis of AIDS (ARR 1.66; 95% CI: 1.29–2.15), being male (ARR 1.79; 95% CI: 1.27–2.53), and with greater experience of the treating physician (ARR 1.27; 95% CI: 1.13–1.42). History of injection drug use was negatively associated with adherence to prescription refill (ARR 0.65; 95% CI: 0.51–0.83), as was increased pill burden (per pill daily) (ARR 0.95; 95% CI: 0.92–0.99). A sub-analysis of 316 patients who provided additional data regarding psychosocial characteristics indicated that adherence was positively associated with physician experience (ARR: 1.28; 95% CI: 1.09–1.51) and being employed (ARR: 1.55; 95% CI: 1.14–2.21), and negatively associated with a history of injection drug use (ARR: 0.61; 95% CI: 0.43–0.85). Conclusion While patient disease stage and personal characteristics may play an important role in patient adherence to prescription refill of complex therapeutic regimens, our findings indicate that HIV-experienced physicians may have greater success in maintaining patients on prescribed therapy.
Effects of Metformin Or Gemfibrozil on the Lipodystrophy of HIV-Infected Patients Receiving Protease Inhibitors
Authors: Martínez Esteban , Domingo Pere , Ribera Esteban , Milinkovic Ana , Arroyo Juan A , Conget Ignacio , Pérez-Cuevas José B , Casamitjana Roser , de Lazzari Elisa , Bianchi Luis , Montserrat Enric , Roca Merce , Burgos Rosa , Arnaiz Juan A , Gatell José M 
Published: April 2022

Background Hypertriglyceridaemia and insulin resistance are common in HIV-infected patients treated with protease inhibitors, particularly in those with lipodystrophy. Whether a therapeutic approach addressed to those metabolic abnormalities may have any impact on body fat is not clear. Methods Patients on stable antiretroviral therapy containing protease inhibitors, with abdominal obesity defined by increased waist-to-hip ratio, and plasma triglycerides >200 mg/dl, were randomized to receive blind medication consisting of metformin 850 mg, gemfibrozil 600 mg or placebo every 12 h for 1 year. Weight, height, waist and hip were measured, and fasting blood analyses, including at least CD4 cell count, plasma HIV-1 RNA, lactate, glucose, insulin, triglycerides, total, HDL and LDL cholesterol were performed at baseline and every 3 months. An oral glucose tolerance test, and assessments of total and regional fat by bioimpedance analysis and sonography, respectively, were also done at baseline, 6 and 12 months. Results One-hundred-and-eight patients were randomized to placebo ( n=36), gemfibrozil ( n=37) or metformin ( n=35). There was absolute loss of total and regional fat in the three arms without significant changes in the waist-to-hip ratio. However, the loss of fat in patients on gemfibrozil was significantly lower than in patients on placebo. No patient discontinued study drugs due to adverse effects. Conclusion In this population of HIV-infected patients, there was a loss of fat along time. The finding of relative preservation of fat associated with gemfibrozil therapy deserves further investigation in the search of potential effective therapies for lipodystrophy in HIV-infected subjects.
Impact of Genotypic Resistance Testing on Selection of Salvage Regimen in Clinical Practice
Authors: Haupts Stefan , Ledergerber Bruno , Böni Jürg , Schüpbach Jörg , Kronenberg Andreas , Opravil Milos , Flepp Markus , Speck Roberto F , Grube Christina , Rentsch Katharina , Weber Rainer , Günthard Huldrych F ,   the Swiss HIV Cohort Study, Bachmann S , Battegay M , Bernasconi E , Bucher H , Bürgisser Ph , Egger M , Erb P , Fierz W , Fischer M , Flepp M , Francioli P , Furrer HJ , Gorgievski M , Günthard H , Grob P , Hirschel B , Kaiser L , Kind C , Klimkait Th , Ledergerber B , Lauper U , Opravil M , Paccaud F , Pantaleo G , Perrin L , Piffaretti J-C , Rickenbach M , Rudin C , Schupbach J , Speck R , Telenti A , Trkola A , Vernazza P , Weber R , Yerly S 
Published: April 2022

Objective To determine whether genotypic resistance testing leads to selection of more potent drug regimens when compared to regimens based on treatment history only. Design Prospective, tertiary care centre-based study. Patients: One-hundred-and-forty-five HIV-infected adults on stable antiretroviral therapy (ART) for >6 months experiencing virological failure. Methods The physicians’ decision-making process when choosing a salvage regimen was prospectively documented: at time of virological failure, on ‘failing ART’, genotyping was performed and a hypothetical ‘clinical expert ART’ based upon patient's drug history was documented. Subsequently, data on resistance mutations, rating by a decision support software and drug history were used to define ‘genotyping ART’. After discussion with the patient, final treatment, ‘new personalized ART’ was chosen and prescribed. To compare the relative potency of the four ART regimens in a standardized manner, a resistance score ranging from 1 (best) to 8 (worst) based on drug ranking by decision support software was attributed to each ART regimen. Virological and immunological outcomes were analysed based on the magnitude of the resistance score. Results Median follow-up was 1.5 years. In all 145 patients, median resistance scores for the stepwise selected ART regimens were: ‘failing ART’: 4.5, ‘clinical expert ART’: 1.8, ‘genotyping ART’: 1.5 and ‘new personalized ART’: 2. The latter was 1.5 in patients who effectively switched to ‘new personalized ART’ ( n=89). Lower resistance scores translated into significantly improved virological response after initiation of ‘new personalized ART’. In multivariable analysis, lower resistance scores, lower baseline HIV RNA levels and use of novel antiretroviral drugs were associated with the probability of reducing plasma viraemia to <50 copies/ml. Conclusions: This study suggests that treatment choices including genotype and decision support software were virologically superior to those based on drug history only.
Sustained Response to Interferon–Ribavirin Combination Therapy Predicted by a Model of Hepatitis C Virus Dynamics Using Both Hcv Rna and Alanine Aminotransferase
Authors: Colombatto Piero , Civitano Luigi , Oliveri Filippo , Coco Barbara , Ciccorossi Pietro , Flichman Diego , Campa Mario , Bonino Ferruccio , Brunetto Maurizia Rossana 
Published: April 2022

Background and aims Standard models simulate the dynamics of hepatitis C virus (HCV) infection using HCV RNA kinetics and show a correlation between the clearance of infected hepatocytes and response to interferon. However, they are unable to predict whether the response will be maintained. The aim of our work was to identify criteria by which sustained responses may be predicted and defined. Methods In our model the clearance rate of infected cells is a function of their number and the baseline rate is computed by the alanine aminotransferase (ALT) kinetics during the first month of therapy. We simulated the variations of viral and infected cell loads in 31 consecutive patients treated with IFN-α2b 3–5 MU every other day, with or without ribavirin, for 6 or 12 months depending on HCV genotype. Results At baseline the computed (in 28 of 31 cases) percentage of infected cells was lower in seven sustained responders (mean: 11.7%, range: 1–24.6%) than in 14 transient responders (mean: 28.2%, range: 7.4–75.5%) and in seven non-responders (mean: 41%, range: 8.8–86%) ( P=0.036). At the end of therapy the computed infected cell number was <100 cells/ml of extracellular fluid in all sustained responders (mean: 18.4, range: 1.7–48), in three transient responders (mean: 3500, range: 1.52–17500) and in none non-responders (mean: 28500, range: 1200–96000) ( P=0.003). Overall of 10 patients with less than 100 infected cells/ml at the end of therapy seven (six had combination therapy) showed sustained response. All three relapsers received interferon monotherapy. Conclusion The analysis of infected cells dynamics using the new model might be useful to tailor treatment duration in patients with combination therapy.
Phenotype or Virtual Phenotype for Choosing Antiretroviral Therapy after Failure: A Prospective, Randomized Study
Authors: Perez-Elias María Jesús , Garcia-Arata Isabel , Muñoz Vicente , Santos Ignacio , Sanz José , Abraira Víctor , Arribas José R , González Juan , Moreno Ana , Dronda Fernando , Antela Antonio , Pumares María , Martí-Belda Paloma , Casado Jose L , Geijo Paloma , Moreno Santiago ,   the Realvirfen study group
Published: April 2022

Background Resistance testing is useful in the management of virological failure patients, although the best method to be used in clinical practice has not been determined. Methods A prospective, randomized, double-blind, multicentre, controlled clinical trial was performed to compare the usefulness of drug resistance testing with a recombinant viral phenotype method or with a virtual phenotype, a genotyping interpretation system. Planned 300 HIV-infected adults failing their current antiretroviral therapy (HIV RNA >1000 copies/ml) were centrally randomized 1:1 to resistance testing with a recombinant viral phenotype method or with a virtual phenotype, after stratifying according to previous drug exposure (one or two versus three drug classes). Percent of patients with HIV RNA suppression (% <400 copies/ml) after 24 weeks was the primary outcome variable. Median HIV RNA concentration and change from baseline in HIV RNA concentration were also used to compare effectiveness. An extended analysis was performed at week 48. Results Of the 300 patients enrolled, a total of 276 patients could be analysed; 139 patients were randomized to the phenotype group and 137 patients were randomized to the virtual phenotype group. After 24 weeks of follow-up, 46.8 and 56.2% of patients had HIV RNA <400 copies/ml ( P=0.1) in the phenotype and virtual phenotype, respectively. Mean decrease from baseline in viral load was 1.0 and 1.3 log copies/ml in the phenotype and virtual phenotype groups, respectively ( P=0.017). In a multivariate linear regression analysis, after adjusting for baseline HIV RNA and adherence to treatment, the virtual phenotype was associated with a greater mean decrease in plasma HIV RNA ( P=0.0063). The results observed at week 48 were similar. Conclusions Virtual phenotype is at least as effective as phenotype when used to select an optimized treatment for patients who have failed one or more antiretroviral regimens.
Efficacy and Safety of Ritonavir/Indinavir 100/400 Mg Twice Daily in Combination with Two Nucleoside Analogues in Antiretroviral Treatment-Naive HIV-Infected Individuals
Authors: Duvivier Claudine , Astriti Myrto , Marcelin Anne-Geneviève , Ghosn Jade , Ait-Mohand Hocine , Schneider Luminita , Agher Rachid , Bricaire François , Costagliola Dominique , Calvez Vincent , Peytavin Gilles , Katlama Christine 
Published: April 2022

Objective To evaluate the efficacy and tolerability of indinavir/ritonavir (IDV/RTV) 400/100 mg twice daily in combination with two nucleoside reverse transcriptase inhibitors in antiretroviral-naive patients. Design and methods Antiviral therapy-naive patients with plasma HIV-1 RNA >5000 copies/ml were enrolled in this pilot, single-arm study. CD4 cell count and viral load were evaluated at weeks (W) 4, 12, 24 and every 3 months until W48. The primary end-point was the percentage (%) of patients with viral load <400 copies/ml at W48. Intent-to-treat (ITT) (missing values or change in treatment equalled failure) and on-treatment (OT) analyses were performed. Results Forty patients were enrolled. Baseline median viral load was 5.36 log10 copies/ml, median CD4 count was 84 cells/mm3. At W48 by ITT analysis, the % patients with viral load <400 copies/ml was 65% (95% CI: 48–79) and 50% (95% CI: 35–65) with viral load <50 copies/ml, and 96% (26/27) (95% CI: 89–100) and 74% (95% CI: 57–91], respectively, by OT analysis. The median decrease in viral load at W48 was –3.83 log10 copies/ml (–0.1; –5.19) and the median increase in CD4 was +167 cells/mm3 (6–474 cell/mm3). At W4 (34/40), the median IDV Cmin was 500 ng/ml (range 5–8100) with 91% of patients with an adequate IDV Cmin >150 ng/ml. Ten patients discontinued the study treatment before W48: adverse events (eight), patient's will (one) and simplification of therapy (one). Three patients were lost to follow-up. Only one virological failure occurred and was associated with poor compliance and sub-optimal concentrations of IDV/RTV. Conclusions IDV/RTV 400/100 mg twice daily is an effective and safe first-line antiretroviral therapy. The simplicity and the low cost of IDV/RTV is of major interest particularly in countries with limited resources.
A Randomized Trial Comparing Initial Haart Regimens of Nelfinavir/Nevirapine and Ritonavir/Saquinavir in Combination with Two Nucleoside Reverse Transcriptase Inhibitors
Authors: Kirk Ole , Lundgren Jens D , Pedersen Court , Mathiesen Lars R , Nielsen Henrik , Katzenstein Terese L , Obel Niels , Gerstoft Jan 
Published: April 2022

Background A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. Methods Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n=118) or ritonavir and saquinavir (400/400 mg twice daily; n=115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ≤20 copies/ml after 48 weeks (missing value=failure). Patients remained under follow-up also in case of switch from the randomized therapy. Results At baseline, the median CD4 cell counts were 126 (range: 0–942) (nelfinavir/nevirapine) and 150 (0–642) (ritonavir/saquinavir) cells/mm3, and HIV RNA measurements 5.0 copies/ml (1.3–6.4) in both groups. A total of 102 (86%) and 101 (88%) were antiretroviral-naive. Within 48 weeks, 35 and 44% discontinued randomized therapy; P=0.13. Of these, 80 and 73% switched therapy due to adverse events; P=0.99. At week 48, 69 and 56%, respectively, had a HIV RNA ≤20 copies/ml; P=0.037. Conclusion A regimen of nelfinavir/nevirapine had a favourable virological effect and tolerability over a 48-week period compared with ritonavir/saquinavir, when administered in combination with two nucleoside reverse transcriptase inhibitors. However, more extensive follow-up is required to determine the long-term consequences of triple class HAART regimens, including the development of broad drug resistance.
The Effect of Number of Mutations and of Drug-Class Sparing on Virological Response to Salvage Genotype-Guided Antiretroviral Therapy
Authors: Ciancio Bruno Christian , Trotta Maria Paola , Lorenzini Patrizia , Forbici Federica , Visco-Comandini Ubaldo , Gori Caterina , Bonfigli Sandro , Bellocchi Maria Concetta , Sette Pietro , D'Arrigo Roberta , Tozzi Valerio , Zaccarelli Mauro , Boumis Evangelo , Narciso Pasquale , Perno Carlo Federico , Antinori Andrea 
Published: April 2022

Objective To assess on longitudinal data the impact of number of drug-associated mutations at genotype resistance testing (GRT) and history of previous exposure to antiretrovirals on the virological response to genotype-guided antiretroviral therapy. Methods Subjects that failed HAART who underwent GRT between June 1999 and March 2002 were enrolled. GRT was performed by Viroseq-2 with expert advice offered to physicians. Main outcome was reaching undetectable (<80 copies/ml) HIV-1 RNA level after GRT and maintaining undetectable viraemia for at least 6 months. The number of mutations conferring resistance to each class of antiretrovirals was categorized and their effect on virological outcome investigated. Mutations considered in the analysis were those reported by the IAS-USA in 2002. Multivariate analysis was performed by Cox proportional hazard model. Results Four-hundred-and-seventy consecutive subjects were enrolled and followed-up for a median of 14 (IQR 9–19) months after GRT. Sustained undetectable viraemia was reached by 80 of 449 subjects (18%). Using as end-point reaching and maintaining for at least 6 months <400 copies/ml after GRT, 103 out of 447 subjects (23%) reached the outcome. For each single protease inhibitor (PI)-, nucleoside reverse transcriptase inhibitor (NRTI)-and non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutation, there was a reduction of, respectively, 11% ( P=0.008), 12% ( P=0.001) and 39% ( P=0.005) in the likelihood of reaching virological outcome. Subjects carrying ≥6 mutations to NRTIs, ≥7 mutations to PIs and ≥2 mutations to NNRTIs were less likely to reach the virological success compared with those carrying 0–1 (NRTI and PI) or 0 (NNRTI) mutations [HR=0.25 (95% CI: 0.10–0.65); HR=0.33 (95% CI: 0.16–0.67); HR=0.33 (95% CI: 0.14–0.77)], respectively. However, at multivariate analysis the probability of reaching a favourable virological outcome in patients with ≥7 mutations to PIs, if naive for NNRTIs [HR=1.74 (0.69–4.36)], and in subjects with ≥2 mutations for NNRTIs if naive for PIs [HR=1.23 (0.22–6.80)], was comparable to those observed in patients with none or one mutation. Conclusions Our data showed a non-linear association between resistance-conferring mutations and virological outcome. GRT-guided therapy still provided remarkable chances of durable virological success even in subjects with ≥7 mutations to PIs and in subjects with ≥2 mutations to NNRTIs, when the subjects did not have a three-class exposure or if GRT showed no evidence of mutations for a drug class. GRT and as-long-as-possible sparing of a drug class could be a convenient strategy for long-term management of drug-failing patients.
Comparison of Antiviral Effect of Lamivudine with Interferon-α2A versus -α2B in Children with Chronic Hepatitis B Infection
Authors: Ozgenc Funda , Dikici Bunyamin , Targan Seref , Doganci Tumay , Akman Sezin , Aydogdu Sema , Yagci Rasit Vural 
Published: April 2022

Aim To compare additive efficacy of combination therapy including interferon (IFN)-α2a+lamivudine (3TC) to IFN-α2b+3TC in children with chronic hepatitis B virus (HBV) infection. Material and methods Chronic hepatitis B infection was determined by presence of HBsAg, HBeAg and HBV DNA in serum screened at 3 months intervals for at least 1 year, serum alanine transaminase (ALT) levels more than 1.5-times the upper normal limit and chronic hepatitis with histological activity index (HAI) more than 6 by liver biopsy. Sixty-three children with chronic hepatitis B infection were treated randomly with thrice-weekly subcutaneous injections of 5 MU/m2 recombinant IFN-α2a ( n=29) or recombinant IFN-α2b ( n=34) with the same dose, intervals for 6 months. Patients also received 3TC (4 mg/kg/day, max 100 mg/day) orally daily combined with IFN and continued for 12 months. End of therapy response was defined as ALT normalization, HBV DNA clearance and HBe/anti-HBe seroconversion. Breakthrough infection was determined as re-emergence of HBV DNA in serum after its clearance. Response rate, incidence of side effects and breakthrough infection were compared between IFN-α2a+3TC- and IFN-α2b+3TC-treated patients. Results Response rate was 44.8% ( n=13) with IFN-α2a+3TC and 47.1% ( n=16) with IFN-α2b+3TC ( P=1.0). No significant difference was found in respect to the DNA clearance ( P=0.32), anti-HBe ( P=1.0), anti-HBs ( P=0.09) seroconversion and response rates ( P=1.0) between the groups. Breakthrough infection was detected in 1 (3.4%) case on IFN-α2a and none of the cases on IFN-α2b ( P=0.46). All of the patients experienced flu-like symptoms, malaise and fatigue; however, side effect interfering with therapy was not encountered. Conclusion No significant difference was found in response rates achieved by combination therapies based on IFN-α2a and IFN-α2b. Clinical efficacy of 3TC and two different IFN subtypes was found similar.
Cost Effectiveness Analysis of Routine Use of Genotypic Antiretroviral Resistance Testing after Failure of Antiretroviral Treatment for HIV
Authors: Corzillius Michael , Mühlberger Nikolai , Sroczynski Gaby , Jaeger Hans , Wasem Jürgen , Siebert Uwe 
Published: April 2022

Objectives Single use of genotypic antiretroviral resistance testing (GART) after first failure of highly active antiretroviral therapy (HAART) was reported to be cost effective; its use prior HAART initiation is unknown. Guidelines recommend GART after each treatment failure. We assessed the cost effectiveness of GART used routinely after first and subsequent treatment failures. Furthermore, we determined the minimum effectiveness required for GART prior to the first HAART to be as cost effective as after treatment failure. Design and methods We developed a decision-analytic Markov model to estimate lifetime clinical and economic outcomes in a cohort of HIV patients starting HAART. Rates of treatment failure, estimates of GART effectiveness and data on disease progression were derived from published trials and observational studies. A cost effectiveness analysis was performed from the perspective of the healthcare system using cost data from a Central European healthcare setting. Deterministic and probabilistic sensitivity analyses using Monte Carlo technique were performed. Results GART after treatment failures increased life expectancy by 9 months and undiscounted life-time costs per case by €16406. The discounted incremental cost effectiveness ratio was €22510 per life-year gained (€/LY). Best- and worst-case scenarios yielded 16 512 €/LY and 42900 €/LY, respectively. GART prior to the initiation of HAART would be equally cost effective if it could reduce the probability of first HAART failure by at least 36%. Conclusion Routine use of GART after treatment failures is cost effective. GART prior to the first HAART would be equally cost effective if it could lower the probability of first HAART failure by approximately a third.