bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial Effects of a 24-Week Course of Pegylated-Interferon plus Ribavirin in Asymptomatic HCV/HIV Co-Infected Patients on Long-Term Treatment with Didanosine, Stavudine or Both
Authors: Ballesteros Àngel Luis , Miró Òscar , López Sònia , Fuster Daniel , Videla Sebastiá , Martínez Eva , Garrabou Glòria , Salas Anna , Côté Hélène , Tor Jordi , Rey-Joly Celestino , Planas Ramon , Clotet Bonaventura , Tural Cristina 
Published: April 2022

Background It has been suggested that the addition of ribavirin (RBV) as a part of the treatment for chronic hepatitis C virus (HCV) in HIV co-infected patients on didanosine (ddI) or stavudine (d4T) might increase the nucleoside-induced impairment of mitochondrial function. Design: Comparative study to investigate the impact on mitochondrial function of adding RBV to a long-term treatment with ddI, d4T or both in HCV/HIV non-cirrhotic, asymptomatic patients. We included 26 patients: 16 continued with their current antiretroviral therapy (control group) and 10 patients received a concomitant 24-week course of RBV plus pegylated interferon (PEG-IFN) α-2b therapy (HCV-treated group). Methods We assessed peripheral blood mononuclear cells mitochondrial DNA (mtDNA) content and mitochondrial respiratory chain (MRC) function at baseline and at 24 weeks of follow-up. In the HCV-treated group we performed additional determinations at 12 weeks during anti-HCV therapy and 24 weeks after finishing anti-HCV therapy. Results Times on ddI or d4T exposure were 194 ±54.9 and 131 ±66.5 weeks in the HCV-treated and control groups, respectively. There were no differences either in mtDNA content, the enzyme activity of MRC complexes or clinical parameters at baseline. Throughout the study, mitochondrial measurements remained stable within groups and without differences when we compared HCV-treated and control groups. Conclusions In our study, the addition of RBV and PEG-IFN during a 24-week period in HCV/HIV non-cirrhotic, asymptomatic patients on long-term ddI, d4T or both had no impact on mitochondrial function. These findings could suggest that additional triggers are required to achieve a critical threshold in the degree of mitochondrial damage needed for symptoms to develop.
Health-Related Quality of Life in HIV Patients Switching to Twice-Daily Indinavir/Ritonavir Regimen or Continuing with Three-Times-Daily Indinavir-Based Therapy
Authors:   the BestQol study group, Badía Xavier , Podzamczer Daniel , Moral Irene , Roset Montse , Arnaiz Joan A , Loncà Montse , Casiró Arnaldo , Rosón Beatriz , Gatell Jose M , Grinberg N , Puentes T , Furst MJ López , Julio Méndez Sanatorio , Lupo S , Suárez C , Agostini M , Cassetti I , Bologna R , Salud Helios , Cahn P , Patterson P , Krolewiecki A , David DO , Luna N , Cruceta A , Pich J , Varea S , Carné X , Mallolas J , Clotet B , Romeu J , Cruz L , Arrizabalaga J , Iribarren JA , Rodríguez F , Von Wichmann MA , Jimeno B , Pulido F , Rubio R , Flores J , González-Lahoz J , Rodríguez-Rosado R , Núñez M 
Published: April 2022

Objective To evaluate health-related quality of life (HRQoL) changes in patients treated with indinavir three-times daily after switching to a twice-daily indinavir/ritonavir regimen or continuing with the same regimen. Methods Patients on HAART including indinavir three-times-daily with undetectable viral load were randomly assigned to continue with this therapy or to change to a twice-daily indinavir/ritonavir (800/100 mg) regimen. The Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire was used as the HRQoL measure. Results A total of 118 patients participated in the study, of which 59 (50%) were randomly assigned to continue with the three-times-daily regimen. Patients had a mean age of 39 years and 80% of them were male. At baseline, subjects included in the three-times-daily group presented a significantly greater number of symptoms than subjects in the twice-daily group, but no statistically significant differences were observed in MOS-HIV scores between the groups. In the intention-to-treat (ITT) analysis, a reduction in HRQoL scores was observed in both groups, which was greater in the twice-daily group. In the per protocol analysis, reduction of HRQoL was minimal. Conclusions A HRQoL deterioration, greater in the twice-daily group, was observed in this study in the ITT analysis, while HRQoL remained stable in both groups in patients who continued with and tolerated the allocated regimen.
Body Fat Changes among Antiretroviral-Naive Patients on Pi- and Nnrti-Based Haart in the Swiss HIV Cohort Study
Authors:   the Swiss HIV Cohort Study, Young Jim , Rickenbach Martin , Weber Rainer , Furrer Hansjakob , Bernasconi Enos , Hirschel Bernard , Tarr Philip E , Vernazza Pietro , Battegay Manuel , Bucher Heiner C , Battegay M , Bernasconi E , Böni J , Bucher H , Bürgisser Ph , Cattacin S , Dubs R , Egger M , Elzi L , Erb P , Fantelli K , Fischer M , Flepp M , Fontana A , Furrer H , Gorgievski M , Günthard H , 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 , Schmid P , Schüpbach J , Speck R , Tarr P , Telenti A , Trkola A , Vernazza P , Weber R , Yerly S 
Published: April 2022

Background Body fat changes are common in patients with HIV. For patients on protease inhibitor (PI)-based highly active antiretroviral therapy (HAART), these changes have been associated with increasing exposure to therapy in general and to stavudine in particular. Our objective is to show whether such associations are more or less likely for patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. Methods We included all antiretroviral-naive patients in the Swiss HIV Cohort Study starting HAART after April 2000 who had had body weight, CD4 cell count and plasma HIV RNA measured between 6 months before and 3 months after starting HAART, and at least one assessment of body fat changes after starting HAART. At visits scheduled every 6 months, fat loss or fat gain is reported by agreement between patient and physician. We estimate the association between reported body fat changes and both time on therapy and time on stavudine, using conditional logistical regression. Results Body fat changes were reported for 85 (9%) out of 925 patients at their first assessment; a further 165 had only one assessment. Of the remaining 675 patients, body fat changes were reported for 156 patients at a rate of 13.2 changes per 100 patient-years. Body fat changes are more likely with increasing age [odds ratio (OR) 1.18 (1.00–1.38) per 10 years], with increasing BMI [OR 1.06 (1.01–1.11)] and in those with a lower baseline CD4 cell count [OR 0.91 (0.83–1.01) per 100 cells/μl]. There is only weak evidence that body fat changes are more likely with increasing time on HAART [OR 1.16 (0.93–1.46)]. After adjusting for time on HAART, fat loss is more likely with increasing stavudine use [OR 1.70 (1.34–2.15)]. There is no evidence of an association between reported fat changes and time on NNRTI therapy relative to PI therapy in those patients who used either one therapy or the other [OR 0.98 (0.56–1.63)]. Conclusion Fat loss is more likely to be reported with increasing exposure to stavudine. We find no evidence of major differences between PI and NNRTI therapy in the risk of reported body fat changes.
Viral Interaction and Responses in Chronic Hepatitis C and B Coinfected Patients with Interferon-Alpha plus Ribavirin Combination Therapy
Authors: Chuang Wan-Long , Dai Chia-Yen , Chang Wen-Yu , Lee Li-Po , Lin Zu-Yau , Chen Shinn-Cherng , Hsieh Ming-Yuh , Wang Liang-Yen , Yu Ming-Lung 
Published: April 2022

Background/aims We conducted a case-control study to investigate the efficacy of interferon-alpha (IFN-α) and ribavirin combination therapy for patients with chronic hepatitis C and B virus (HCV/HBV) coinfection and to elucidate the interaction of these two viruses. Methods Forty-two chronic HCV/HBV-coinfected patients (29 IFN-naive, 13 IFN-relapsed) and 84 HCV-monoinfected controls, matched for age, sex and previous history of IFN-α therapy, were enrolled. All patients were treated with IFN-α-2b 6 MU three-times weekly plus ribavirin 1000–1200 mg daily for 24 weeks. Serum HCV RNA and HBV DNA were determined every 24 weeks for 72 weeks. Results The rate of HCV sustained virological response (SVR) was comparable among IFN-naive and IFN-relapsed HCV/HBV-coinfected patients and IFN-naive and IFN-relapsed HCV-monoinfected patients (69.0%, 69.2%, 67.2% and 57.7%, respectively; intention-to-treat analysis). HCV genotype 1b, high pretreatment HCV RNA levels and liver fibrosis were significantly associated with a lower HCV SVR. Of 16 baseline HBV viraemic patients, five (31.3%) achieved HBV SVR, which correlated negatively to HCV genotype non-1b and HCV SVR. Only one (6.3%) had simultaneous seroclearance of HCV and HBV. Antibodies to HBV surface antigen seroconversion developed in five (11.9%) patients during long-term follow-up. HCV responders had significantly higher rates of HBV DNA resurgence than HCV non-responders during and after treatment. Reciprocal viral interference was noted between HCV and HBV after IFN-α/ribavirin therapy. Conclusions IFN-α/ribavirin combination therapy is effective for HCV/HBV-coinfected patients in eradicating HCV infection and might promote HBV seroclearance, and there is a mutual viral response and reciprocal viral interaction between HBV and HCV.
Changes in Mitochondrial Rna Production in Cells Treated with Nucleoside Analogues
Authors: Galluzzi Lorenzo , Pinti Marcello , Troiano Leonarda , Prada Nicole , Nasi Milena , Ferraresi Roberta , Salomoni Paolo , Mussini Cristina , Cossarizza Andrea 
Published: April 2022

Background To investigate mitochondrial (mt) toxicity of antiretroviral drugs further, we developed a novel realtime PCR-based assay for the quantification of mtRNA. We analysed the effects of stavudine (d4T), didanosine (ddI) and zidovudine (AZT) on the production of mtRNAs in different human cell lines and compared the production with the amount of mtDNA present in the same cells. Materials and methods: HUT78, CEM and U937 cells were exposed to different nucleoside reverse transcriptase inhibitors (NRTIs) for 7 days. Thereafter, nucleic acids were isolated and Taqman-based real-time PCR was used to quantify mtDNA and three different mtRNAs (ND1, CYTB and ND6 gene products). Results Different amounts of mtRNAs exist in different cell lines. When mtRNA was measured in cells exposed to an NRTI, a marked decrease was observed in cells treated with d4T, but not with ddI or AZT. Changes in mtRNA production did not always correspond to modifications in mtDNA content: 1 μM d4T significantly changed mtRNA but not mtDNA content. Conclusions d4T, but not ddI or AZT, significantly alters mtRNA quantity and quality. The method we have developed can reveal changes that are not observed by measuring mtDNA content only, and can be used for ex vivo studies on drug toxicity.
Early Virological Failure with a Combination of Tenofovir, Didanosine and Efavirenz
Authors: Podzamczer Daniel , Ferrer Elena , Gatell Josep Maria , Niubo Jordi , Dalmau David , Leon Agathe , Knobel Hernando , Polo Carolina , Iniguez Daniel , Ruiz Isaac 
Published: April 2022

Objective To describe the occurrence of a high early virological failure (VF) rate and development of resistance mutations in antiretroviral-naive patients receiving tenofovir, didanosine and efavirenz. Methods HIV-infected antiretroviral-naive patients with viral load ≥30 000 copies/ml were enrolled in a pilot randomized trial of tenofovir/didanosine (250 mg)/ efavirenz with (arm A) or without (arm B) lopinavir/r for the first 12 weeks. As six cases of early VF (a drop of <2 log at month 3, or a rebound of >1 log from the nadir) were detected (five in arm B and one in arm A who had previously stopped lopinavir/r) an unplanned interim analysis was performed. Results A total of 29 out of 36 enrolled patients completed at least 3 months of follow-up and were included in the interim analysis. An intent-to-treat analysis showed treatment failure in 7/15 (46.7%) patients in arm B (five VF, one lost, one switched) versus 2/14 (14.3%) in arm A (one lost, one switched) ( P=0.109). The patient in arm A who interrupted lopinavir/r at day 3 and continued with tenofovir/didanosine/efavirenz later developed VF. At baseline, 6/6 VF patients had VL >100 000 copies/ml and an advanced stage of disease (CD4 <200 plus CDC stage C or B3) versus 0/8 non-VF patients taking the triple drug regimen ( P<0.001). At failure, G190S/E alone or associated with K103N and K101R mutations was detected in five patients, and K103N/L100I/V108I in the sixth patient. Additionally, L74V/I and K65R were detected in four and two patients, respectively. Conclusions A high early virological failure rate and the occurrence of resistance mutations were detected in a group of antiretroviral-naive patients treated with tenofovir/didanosine/efavirenz. Presented in part at the 13th International HIV Drug Resistance Workshop. 8–12 June 2004, Tenerife. Abstract 156.
Altered Adipokine Response in Murine 3T3-F442A Adipocytes Treated with Protease Inhibitors and Nucleoside Reverse Transcriptase Inhibitors
Authors: Jones Simon P , Janneh Omar , Back David J , Pirmohamed Munir 
Published: April 2022

Background Abnormal levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and adiponectin have been observed in HIV patients with lipodystrophy. However, because these patients have long drug and disease histories, it is unclear which drugs are responsible for these abnormalities. We have therefore investigated the effects of individual antiretrovirals on adipokine expression and adipogenesis using a murine cell line in vitro. Methods Differentiating murine 3T3-F442A adipocytes were incubated with 20 μM nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine or stavudine, or protease inhibitors (PIs) indinavir, ritonavir, saquinavir or nelfinavir, in the presence and absence of rosiglitazone (10 μM). Adipogenesis was assessed using glycerol-3-phosphate dehydrogenase activity, while expression of TNF-α, IL-6 and adiponectin at protein and mRNA levels was assessed by ELISA and quantitative real-time PCR, respectively. Results Nelfinavir, ritonavir and saquinavir inhibited adipogenesis and up-regulated the expression of TNF-α and IL-6, but this effect was not seen with indinavir, zidovudine and stavudine. Adiponectin expression was significantly reduced in both NRTI- and PI-treated cells, although the most profound reductions were found with ritonavir and saquinavir. Co-incubation with rosiglitazone led to a partial attenuation of the change in TNF-α, IL-6 and adiponectin secretion. Conclusions Our data suggest that the PIs nelfinavir, ritonavir and saquinavir have potent effects in inhibiting adipocyte differentiation whilst up-regulating TNF-α and IL-6 mRNA levels and decreasing adiponectin levels. These changes were partially attenuated by rosiglitazone. Taken together, the data show that antiretrovirals have complex effects on adipocyte function, which may be mediated by an altered adipokine response.
Field Assessment of Generic Antiretroviral Drugs: A Prospective Cohort Study in Cameroon
Authors: Bourgeois Anke , Laurent Christian , Mougnutou Rose , Nkoué Nathalie , Lactuock Bernadette , Ciaffi Laura , Liégeois Florian , Andrieux-Meyer Isabelle , Zekeng Léopold , Calmy Alexandra , Mpoudi-Ngolé Eitel , Delaporte Eric 
Published: April 2022

Objective To assess the effectiveness of generic anti-retroviral drugs in terms of survival and virological and immunological responses, as well as their tolerability and the emergence of viral resistance. Methods A total of 109 HIV-1-infected patients were enrolled in a prospective cohort study in Yaoundé, Cameroon. Available generic drugs were a fixed-dose combination (FDC) of zidovudine (ZDV) and lamivudine (3TC), an FDC of 3TC, stavudine (d4T) and nevirapine (NVP), and individual formulations of ZDV, 3TC and NVP. Results At baseline, the median CD4 cell count was 150/mm3 [interquartile range (IQR) 61–223] and median viral load was 5.4 log10 copies/ml (IQR 4.8–5.6); 78% of patients received ZDV/3TC/NVP and 22% received 3TC/d4T/NVP. Median follow-up was 16 months (IQR 11–23). The survival probability was high (0.92 at 12 months); plasma viral load declined by a median of 3.3 log10 copies/ml and 86.9% of the intention-to-treat population had viral load <400 copies/ml at 12 months; CD4 count had increased by a median of 106 cells/mm3 at 12 months; drug resistance rarely emerged (incidence rate 3.2 per 100 person-years); and the treatments were reasonably well-tolerated (incidence rate of severe adverse effects 7.8 per 100 person-years). Conclusion Together with previous pharmacological and clinical studies, this prospective study suggests that these generic antiretroviral drugs can be used in developing countries.
Lamivudine Treatment in Hbeag-Negative Chronic Hepatitis B Patients with Low Level Viraemia
Authors: Bozkaya Hakan , Yurdaydin Cihan , Idilman Ramazan , Tüzün Ali , Cinar Kubilay , Erkan Özlem , Bozdayi A Mithat , Erden Esra , Uzun Yusuf , Cetinkaya Hülya , Uzunalimoglu Özden 
Published: April 2022

Background Our aim was to determine the short-term natural course of viraemia and the response to lamivudine treatment in HBeAg-negative chronic hepatitis B patients with a persistently low hepatitis B virus (HBV)-DNA level. Methods A total of 55 patients were included. Group 1 consisted of 37 patients with low-level viraemia and high serum alanine aminotransferase (ALT) levels and further randomized to two groups: group 1a ( n=19) patients received 1 year of lamivudine therapy and group 1b ( n=18) patients were untreated controls. Group 2 consisted of 18 inactive carriers who were followed as controls of untreated low viraemic chronic hepatitis B patients. HBV DNA was longitudinally determined by real-time polymerase chain reaction assay. Results A female predominance in group 2 was observed while males were predominant in group 1. Mean age and baseline HBV-DNA levels did not differ between group 1 and 2 patients while group 1 patients had a higher histological score ( P<0.01). Of group 1a patients, 44% had complete ALT normalization at end of treatment, whereas 21% untreated group 1b patients had normal ALT at the end of the follow-up. No change in histological activity was observed in group 1a patients at the end of treatment. HBV-DNA levels did not significantly change from baseline to end-of-treatment/observation period in patient groups. The viraemia course was not different across the groups. Conclusions Low viraemic HBeAg-negative patients with high ALT present with minimal/mild histological activity. Inactive carriers cannot be differentiated from low viraemic patients with high ALT based on HBV DNA determination. Although lamivudine treatment can be effective in some cases, observation rather than a prompt treatment attempt seems to be more logical because of mild histological changes and low response rate to treatment in these patients.
Open, Randomized, Multicentre Italian Trial on Peg-Ifn plus Ribavirin versus Peg-Ifn Monotherapy for Chronic Hepatitis C in HIV-Coinfected Patients on Haart
Authors:   the Italian Co-infection Study (ICOS) Group, Cargnel Antonietta , Angeli Elena , Mainini Annalisa , Gubertini Guido , Giorgi Riccardo , Schiavini Monica , Duca Piergiorgio , Scalise G , Cesare S Di , Chiodo F , Verucchi G , Farci P , Serra G , Sagnelli E , Nacca C , Ferraro T , Scerbo A , Santoro D , Pusterla L , Viganò P , Magnani C , Ghinelli F , Sighinolfi L , Vigevani G , Pastecchia C , Moroni M , Milazzo L , Esposito R , Borghi V , Piccinino F , Filippini P , Cadrobbi P , Sattin A , Ferrari C , Antoni A Degli , Stagni G , Francisci D , Petrelli E , Alberici F , Sacchini D , Zauli T , Donà D De , Arlotti M , Mori F , Marranconi F , Caramello P , Lipani F , Soranzo ML , Macor A , Vaglia A , Rossi MC , Grossi P , Tambini R , De Lalla F , Tositti G 
Published: April 2022

Background Chronic hepatitis C is common and aggressive in HIV-positive patients, so the development of a well-tolerated HCV therapy is a priority. We evaluated the efficacy and safety of pegylated interferon α2b (PEG-IFN) plus ribavirin (RBV) versus PEG-IFN monotherapy in HIV/HCV-coinfected patients undergoing highly active antiretroviral therapy (HAART), and analysed the predictive factors of response. Methods An Italian, multicentre, open-label trial including 135 coinfected patients, randomized to PEG-IFN 1.5 μg/kg/week plus RBV 400 mg twice daily ( n=69, arm A) or PEG-IFN 1.5 μg/kg/week ( n=66, arm B) for 48 weeks. We assessed the predictive values of early virological response (EVR) at week 8 (HCV-RNA drop >2 log10 compared with baseline or undetectable levels) on sustained virological response (SVR). Results Fifty-five patients (28 from arm A and 27 from arm B) completed 48 weeks of therapy. At the end of treatment, 20/28 patients in arm A and 11/27 in arm B had HCV-RNA <50 IU/ml. In a per-protocol analysis, SVR was reached by 54% of patients in arm A (genotype 2–3, 11/16; genotype 1–4, 4/12) and 22% in arm B (genotype 2–3, 3/15; genotype 1–4, 3/12). In an intention-to-treat analysis, the SVR was 22% in arm A (genotype 2–3, 11/32; genotype 1–4, 4/37) versus 9% in arm B (genotype 2–3, 3/32; genotype 1–4, 3/34). The best predictors of SVR were the use of combination therapy, infection with HCV genotype 3 versus genotype 1, and EVR at week 8. Thirty patients (15 from arm A and 15 from arm B) dropped out of the trial prematurely due to side effects. The positive predictive value of EVR at week 8 was 65%, the negative predictive value was 86%. Conclusions PEG-IFN plus RBV can be considered a solid option for the treatment of HIV/HCV-coinfected patients. The key to successfully improving efficacy is strong compliance through strict overall patient monitoring, in order to best manage drug toxicity. EVR assessment at week 8 may become a useful stategy in the management of therapy.
HBV-DNA Suppression and Disease Course in HBV Cirrhosis Patients on Long-Term Lamivudine Therapy
Authors: Di Marco Vito , Stefano Rosa Di , Ferraro Donatella , Almasio Piero Luigi , Bonura Celestino , Giglio Maria , Parisi Pietro , Cappello Maria , Alaimo Giuseppe , Craxì Antonio 
Published: April 2022

In hepatitis B virus (HBV) cirrhosis patients on long-term lamivudine (LAM), the relationships between HBV suppression, development of viral resistance and disease outcome are unclear. We analysed the dynamic of serum HBV-DNA and its relationship with the clinical course of 59 patients (52 males, mean age 51.4 ±8.4 years, 12 HBeAg positive and 47 HBeAg negative, and 57 genotype D and two genotype A) with cirrhosis (45 in Child-Turcotte-Pugh class A) and high levels of serum HBV-DNA (median 14.7x107 genomes/ml) treated with LAM [median (range): 44 (15–78) months]. A total of 50 patients (84.7%) achieved a virological response (serum HBV-DNA negative by PCR) during the first 6 months of therapy, and nine (13.3%) achieved a reduction in viral load of >3 log10. Mutations in the YMDD motif of HBV polymerase were documented in 26 patients [median (range) 18: (7–42) months]. At the time of the emergence of mutants, 22 patients had HBV-DNA <105 genomes/ml and normal alanine aminotransferase (ALT) levels. The appearance of virological resistance was followed by an increase of HBV-DNA to ≥105 genomes/ml and of ALT values in 19 out of 26 patients [median (range): 8 (3–19) months]. Event-free survival was significantly longer ( P=0.001) in patients who maintained virological suppression than in those who did not have a complete virological response or suffered a breakthrough. Patients with advanced cirrhosis were more likely to develop liver failure after the emergence of YMDD mutants. The risk of development of hepatocellular carcinoma in patients with compensated cirrhosis and YMDD mutations was maintained, regardless of HBV-DNA serum levels. Profound and maintained HBV-DNA suppression correlates with a better outcome. Early identification of LAM resistance mutations allows switching to other antivirals before liver decompensation or hepatocellular carcinoma development.