bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1-Resistant Strains during 8-Week on 8-Week off Intermittent Therapy and their Effect on CD4+ T-cell Counts and Antiviral Response
Authors: Izopet Jacques , Marchou Bruno , Charreau Isabelle , Sauné Karine , Tangre Philippe , Molina Jean-Michel , Jean-Pierre Aboulker ,   for the Window (ANRS 106) Study Team
Published: April 2022

Background We aimed here to study drug-associated HIV resistance mutations in peripheral blood mononuclear cells (PBMC) and plasma during intermittent therapy. Methods A substudy of 86 patients randomized to the intermittent treatment arm (8-week on/8-week off) of the ANRS 106 Window trial. HIV reverse transcriptase and protease genes were sequenced and resistance mutations identified according to the International AIDS Society list. Results Resistance mutations were detected in PBMC of 27/86 (31%) patients at baseline and 25/72 (35%) patients at week 96. Resistance mutations were detected in plasma of 28/86 (33%), 24/83 (29%) and 33/80 (41%) patients at weeks 8, 40 and 88, respectively. The detection of nucleoside reverse transcriptase inhibitor and protease inhibitor associated resistance mutations in plasma remained stable over time, but there was an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated resistance mutations in patients on an NNRTI-based regimen: 1/33 (3%) versus 7/26 patients (27%) at weeks 8 and 88, respectively ( P=0.02). The proportions of patients with plasma HIV RNA levels ≤400 copies/ml after 8 weeks of treatment at weeks 16, 48 and 96 in patients with drug-resistant and wild-type viruses were 93% versus 74% ( P=0.04), 96% versus 88% ( P=0.43) and 70% versus 84% ( P=0.13), respectively. Patients with drug-resistant virus had a lower CD4+ T-cell decrease from baseline at weeks 40 and 88 as compared to patients with wild-type virus ( P=0.05 and 0.002, respectively). Conclusions NNRTI-associated resistance mutations increased over time in plasma of patients who were given NNRTIs. Drug-associated HIV resistance mutations did not seem to impair short-term antiviral response and might be associated with reduced CD4+ T-cell loss during interruptions.
Pegylated Interferon-α2b plus Ribavirin: An Efficacious and well-Tolerated Treatment Regimen for Patients with Hepatitis C virus Related Histologically Proven Cirrhosis
Authors: Roff Luigi , Colloredo Guido , Pioltelli Pietro , Bellati Giorgio , Pozzi Massimo , Parravicini Pierpaolo , Bellia Valentina , Del Poggio Paolo , Fornaciari Giovanni , Ceriani Roberto , Ramella Giuliano , Corradi Chiara , Rossini Angelo , Bruno Savino 
Published: April 2022

Background Little is known about the efficacy, safety and tolerability of pegylated interferon plus ribavirin treatment in patients with chronic hepatitis C virus (HCV) infection and histologically proven fully established cirrhosis. We aimed here to evaluate the safety of this regimen in such patients and to identify baseline and on-treatment predictors of a sustained virological response (SVR). Methods Patients with histologically proven, HCV-induced cirrhosis were randomized to receive pegylated interferon-α2b (PEG-IFN-α2b; 1.0 μg/kg/week, n=56; group A) or recombinant interferon-α2b (IFN-α2b; 3 million IU three times/week, n=36; group B), each in combination with a weight-based dose of ribavirin (800–1,200 mg/day) for up to 48 weeks. The primary endpoint of the study was the assessment of SVR, defined as undetectable HCV RNA 24 weeks after treatment cessation. Results Overall, 40% (37/93) of patients attained SVR: 44% (25/57) in group A and 33% (12/36) in group B ( P=0.31). SVR rates were significantly higher in genotype 2/3 patients than in genotype 1 patients (69% versus 25%; P<0.0001). Platelet count at baseline, rapid virological response, and early virological response were predictors of SVR. Twelve patients discontinued treatment because of an adverse event and 20 patients required ribavirin dose reduction for the management of anaemia. Conclusions PEG-IFN-α2b plus ribavirin for 48 weeks is an efficacious and well-tolerated treatment regimen for patients with HCV-induced cirrhosis. Although SVR rates were more satisfactory in genotype 2/3 than in genotype 1 patients, our study identified additional predictors of response that could allow physicians to better manage treatment in this ‘difficult-to-cure’ subset of patients.
Incidence of abacavir hypersensitivity reactions in EuroSIDA
Authors: Bannister Wendy P , Friis-Møller Nina , Mocroft Amanda , Viard Jean-Paul , van Lunzen Jan , Kirk Ole , Gargalianos Panagiotis , Bánhegyi Dénes , Chiesi Antonio , Lundgren Jens D ,   the EuroSIDA study group
Published: April 2022

Background The aim of the study was to investigate the incidence of abacavir-related hypersensitivity reaction (HSR) and associated deaths in EuroSIDA HIV-1-infected patients. Methods Poisson regression models were developed to compare incidence of abacavir discontinuation according to the line of therapy within which abacavir was received, geographical regions, calendar time and drug formulation (abacavir/lamivudine combination tablet versus abacavir as a single drug or abacavir/zidovudine/ lamivudine combination). Results Of 3,278 patients that started abacavir, 2,101 (64.1%) discontinued. Of these, 167 (5.1%) discontinued abacavir within 3 months due to HSR with an incidence of 22.1 (95% confidence interval [CI] 18.7–25.4) per 100 person-years of follow-up. After adjustment for gender, prior AIDS, hepatitis C serostatus, baseline CD4+ T-cell count, region and calendar time, HSR incidence was significantly higher in those starting abacavir in a first-line regimen compared with second-line (incidence rate ratio [IRR] 2.04 [95% CI 1.24–3.38]; P=0.005). There was no significant difference between regions. HSR incidence from 2005 onwards was significantly lower compared with 1999–2000 (IRR 0.54 [95% CI 0.32–0.92]; P=0.024). There was a lower observed incidence in patients starting abacavir/lamivudine compared with other formulations (IRR 0.33 [95% CI 0.13 –0.88]; P=0.027), however, available data were limited. Conclusions Incidence of abacavir-related HSR is higher in patients starting abacavir in first-line therapy, which could indicate increased over-diagnosis. HSR incidence has decreased in recent years, which might reflect the wider availability of genetic screening and improved awareness of symptoms. There were no reported deaths due to abacavir HSR.
Comparison of the antiviral activity of adefovir and tenofovir on hepatitis B virus in HIV–HBV-coinfected patients
Authors: Lacombe Karine , Gozlan Joël , Boyd Anders , Boelle Pierre-Yves , Bonnard Philippe , Molina Jean-Michel , Miailhes Patrick , Lascoux-Combe Caroline , Serfaty Lawrence , Zoulim Fabien , Girard Pierre-Marie 
Published: April 2022

Background Characteristics and factors influencing viral decay under tenofovir (TDF) and adefovir (ADV) need to be determined in HIV–HBV-coinfected patients. Methods This open-label study compared the HBV dynamics in 85 HIV–HBV-coinfected patients initiating an antiretroviral regimen, either including TDF or associated with ADV. The first 6-month change in viral load was analysed using mixed linear models. The adjusted hazards ratio, comparing the rates of undetectable HBV DNA between treatments, was calculated using a Cox proportional hazard model. Results The HBV DNA decay, adjusted for baseline HBV viral load was more pronounced in patients treated with TDF than with ADV at 12 months (66% versus 53%, P=0.0001). Patients in the TDF group presented a steeper slope of decline at 1.1 (95% confidence interval [CI] 0.9–1.3), compared with 0.8 (95% CI 0.6–1.0) in the ADV group ( P=0.036). The mean time to HBV DNA undetectability was 19.3 months (95% CI 16.7–22.0) with TDF and 25.9 months (95% CI 21.1–30.7) with ADV. When adjusted for hepatitis B virus e antigen, HBV DNA and alanine aminotransferase levels at baseline, the influence of treatment on time to HBV DNA undetectability remained in favour of TDF versus ADV (hazard ratio=2.79, 95% CI 1.05–7.40, P=0.039) Conclusions TDF influenced more strongly the early-phase HBV DNA kinetics than ADV. This is associated with a sustained antiviral activity in the TDF group, in which patients reached the threshold of HBV undetectability at a faster rate and in a larger proportion than those taking ADV.
Variability in the Plasma Concentration of Efavirenz and Nevirapine is Associated with Genotypic Resistance after Treatment Interruption
Authors: Darwich Laila , Esteve Anna , Ruiz Lidia , Bellido Rocio , Clotet Bonaventura , Martinez-Picado Javier 
Published: April 2022

Background Selection and persistence of non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutations during treatment interruptions (TIs) has been attributed to the long plasma half-life of these drugs. However, little is known about the contribution of variable NNRTI plasma levels before a TI. We evaluated the selection of NNRTI-related mutations and the coefficient of variation of NNRTI plasma concentrations during different TI periods. Methods The selection of NNRTI-related mutations was examined in 50 HIV type-1 (HIV-1)-infected patients on a virologically suppressive regimen who underwent TI guided by CD4+ T-cell counts and plasma viraemia. Population and clone-based sequencing of the reverse transcriptase coding region was performed using plasma HIV-1 RNA samples during TI and proviral DNA from peripheral blood mononuclear cells before TI. NNRTI plasma concentrations were determined by HPLC. Results In 7/50 treated patients, de novo and transient NNRTI-related mutations appeared when treatment was interrupted. Emergence of resistant variants (including K103N, Y181C or G190S) after interruption was associated with a higher coefficient of variation in NNRTI plasma concentrations during the treatment period. Moreover, minority HIV-1 variants containing different resistance patterns (V106I/A, K103R/E or Y188C/D/H) were detected regardless of NNRTI concentrations. Conclusions The emergence of NNRTI-associated mutations during TI appears to be associated with the variation of NNRTI plasma concentrations during the preceding treatment period. The selection of minority HIV-1 variants with different patterns of NNRTI resistance in the absence of drug pressure should be considered for the efficacy of future NNRTI-containing antiretroviral regimens.
HIV Coinfection and Antiretroviral Therapy Enhances Liver Steatosis in Patients with Hepatitis C, but Only in those Infected by HCV Genotype other than 3
Authors: Borghi Vanni , Puoti Massimo , Mussini Cristina , Bellelli Stefania , Angeletti Claudio , Sabbatini Francesca , Prati Francesca , Cossarizza Andrea , Esposito Roberto 
Published: April 2022

Background Liver steatosis is a common finding in hepatitis C virus (HCV) infection and is associated with an increased progression of the disease. However, HCV genotype 3 steatosis presents a peculiar and virus-induced pathogenesis. We analysed the effect of HIV coinfection and antiretroviral therapy on hepatic steatosis and the effect of the steatosis on fibrosis in patients with or without HCV genotype 3 infection. Methods All consecutive HIV-infected and uninfected patients who had undergone a liver biopsy for evaluation of HCV infection at the Infectious Diseases Clinic (Modena, Italy) were included in this study. Primary outcomes were the presence or absence of steatosis or the presence of moderate or advanced fibrosis. Results A total of 284 patients were enrolled: 187 infected by HCV and 97 coinfected with HIV and HCV. In HCV genotype 3 patients, only HCV-related variables, such as plasma HCV RNA levels (odds ratio [OR] per log10 1.68, P<0.001) and estimated duration of HCV infection (OR per year 1.17, P=0.004) were associated with steatosis. In patients infected with other HCV genotypes, steatosis was associated with older age (OR per 5 years 1.47, P<0.001), with exposure to d-drugs in HIV–HCV-coinfected patients (OR 2.60, P=0.04) and specifically exposure to stavudine (OR 2.76 HIV–HCV-coinfected versus not HIV-infected patients, P=0.04). Steatosis was independently associated with bridging fibrosis only in patients infected by HCV genotype other than 3 (OR 4.03, P=0.01). Conclusions Hepatic steatosis, in both HCV-monoinfected and in HIV–HCV-coinfected patients, is strongly correlated with HCV genotype 3, probably through interactions between HCV virus and liver cells. HIV-related increase of steatosis in patients with HCV is probably related to anti-retroviral drugs, especially stavudine, in patients infected by HCV genotype other than 3.
Prognostic Importance of Anaemia in HIV Type-1-Infected Patients Starting Antiretroviral Therapy: Collaborative Analysis of Prospective Cohort Studies
Authors:   The Antiretroviral Therapy Cohort Collaboration, Harris Ross J , Sterne Jonathan AC , Abgrall Sophie , Dabis François , Reiss Peter , Saag Michael , Phillips Andrew N , Chêne Geneviève , Gill John M , Justice Amy C , Rockstroh Jürgen , Sabin Caroline A , Mocroft Amanda , Bucher Heiner C , Hogg Robert S , Monforte Antonella D'Arminio , May Margaret , Egger Matthias 
Published: April 2022

Background In HIV type-1-infected patients starting highly active antiretroviral therapy (HAART), the prognostic value of haemoglobin when starting HAART, and of changes in haemoglobin levels, are not well defined. Methods We combined data from 10 prospective studies of 12,100 previously untreated individuals (25% women). A total of 4,222 patients (35%) were anaemic: 131 patients (1.1%) had severe (<8.0 g/dl), 1,120 (9%) had moderate (male 8.0–<11.0 g/dl and female 8.0–<10.0 g/ dl) and 2,971 (25%) had mild (male 11.0–<13.0 g/dl and female 10.0–<12.0 g/dl) anaemia. We separately analysed progression to AIDS or death from baseline and from 6 months using Weibull models, adjusting for CD4+ T-cell count, age, sex and other variables. Results During 48,420 person-years of follow-up 1,448 patients developed at least one AIDS event and 857 patients died. Anaemia at baseline was independently associated with higher mortality: the adjusted hazard ratio (95% confidence interval) for mild anaemia was 1.42 (1.17–1.73), for moderate anaemia 2.56 (2.07–3.18) and for severe anaemia 5.26 (3.55–7.81). Corresponding figures for progression to AIDS were 1.60 (1.37–1.86), 2.00 (1.66–2.40) and 2.24 (1.46–3.42). At 6 months the prevalence of anaemia declined to 26%. Baseline anaemia continued to predict mortality (and to a lesser extent progression to AIDS) in patients with normal haemoglobin or mild anaemia at 6 months. Conclusions Anaemia at the start of HAART is an important factor for short- and long-term prognosis, including in patients whose haemoglobin levels improved or normalized during the first 6 months of HAART.
Low-dose Cidofovir for the Treatment of Polyomavirus-Associated Nephropathy: Two Case Reports and Review of the Literature
Authors: Lamoth Frédéric , Pascual Manuel , Erard Véronique , Venetz Jean-Pierre , Nseir Ghaleb , Meylan Pascal 
Published: April 2022

Background Polyomavirus-associated nephropathy (PVAN) is a serious complication and cause of graft loss in kidney transplant recipients. In the absence of specific antiviral drugs, early detection of the disease and reduction of immunosuppressive regimen is the cornerstone of therapy. Cidofovir, a nucleoside analogue, has been found to inhibit BK virus (BKV) replication in vitro and has been proposed as treatment of refractory PVAN at low doses; however, its efficacy has never been demonstrated in randomized controlled trials. Methods Cidofovir therapy (0.5 mg/kg at a 2-week interval for eight consecutive doses) was initiated in two patients with biopsy-proven PVAN and persistent BKV DNA viraemia (≥10,000 copies/ml despite sustained reduction of the immunosuppressive regimen). In addition to these two case reports, we performed a critical review of the literature on the use of cidofovir in PVAN. Results No significant decrease of BKV viral load in blood was observed during cidofovir therapy and in follow-up of the two patients treated with cidofovir. Our literature review identified 21 publications reporting the use of cidofovir for the treatment of PVAN. All were case reports or small series. The efficacy of cidofovir therapy could not be assessed in 17 of these publications because of lack of data or concomitant reduction of immunosuppressive regimen. The four remaining publications were case reports. Conclusions In vitro and clinical data to support the efficacy of cidofovir in the treatment of PVAN are currently lacking. More promising compounds should be identified for further clinical studies.
Pharmacokinetics, Safety and Efficacy of Saquinavir/ Ritonavir 1,000/100 Mg Twice Daily as HIV Type-1 Therapy and Transmission Prophylaxis in Pregnancy
Authors: von Hentig Nils , Nisius Gabi , Lennemann Tessa , Khaykin Pavel , Stephan Christoph , Babacan Errol , Staszewski Schlomo , Kurowski Michael , Harder Sebastian , Haberl Annette 
Published: April 2022

Background A saquinavir/ritonavir-containing regimen is one option for the prevention of mother-to-child transmission of HIV during pregnancy. We evaluated the pharmaco-kinetics, efficacy and safety of saquinavir/ritonavir 1,000/100 mg twice daily plus nucleos(t)ide reverse transcriptase inhibitors in 13 women during late pregnancy and compared the results to those of 15 non-pregnant women. Methods Protease inhibitor plasma concentration profiles were assessed at 12 h using a standardized therapeutic drug monitoring procedure and measured by LC-MS/MS. Minimum and maximum concentrations (Cmin and Cmax), area under the plasma concentration–time curve (AUC0–12 h), and total clearance (CL total) were compared between the groups and correlated to demographic, physiological and clinical cofactors. Antiviral and immunological efficacy and safety were investigated. Results The geometric means (90% confidence interval [CI]) for saquinavir Cmin, Cmax and AUC0–12 h of pregnant versus non-pregnant women were 572 (437–717) versus 765 (485–1,052, P=0.064) ng/ml, 2,168 (1,594–2,807) versus 3,344 (2,429–4,350; P=0.045) ng/ml and 15,512 (11,657–19,943) versus 24,027 (17,454–31,548, P=0.029) ng•h/ml. The geometric means (90% CI) for ritonavir Cmin, Cmax and AUC0–12 h were 190 (148–234) versus 310 (240–381, P=0.011) ng/ml, 781 (580–999) versus 1,552 (1,127–2,007, P=0.004) ng/ml and 5,576 (4,303–7,006) versus 10,528 (8,131–13,177, P=0.003) ng•h/ml. Age, weight, saquinavir dose per weight and body mass index differed significantly; saquinavir Cmin and AUC0–12 h were correlated with ritonavir Cmin and saquinavir dose per weight. After a mean of 11 weeks treatment, 12 of 13 pregnant women had a viral load <400 copies/ml, which was similar to the results of non-pregnant women. Conclusions Although saquinavir plasma concentrations were significantly lower in pregnant women compared with non-pregnant women, all pregnant women displayed a saquinavir AUC0–12 h>10,000 ng•h/ml, 92.3% had a viral load <400 copies/ml at birth. Saquinavir was well tolerated by the mothers and all newborn children were HIV type-1 negative at 18 months of age.
Early warning indicators for HIV drug resistance in Malawi
Authors: Hedt Bethany L , Wadonda-Kabondo Nellie , Makombe Simon , Harries Anthony D , Schouten Erik J , Limbambala Eddie , Hochgesang Mindy , Aberle-Grasse John , Kamoto Kelita 
Published: April 2022

Background Malawi started rapid scale-up of antiretroviral therapy (ART) in 2004 and by December 2006 had initiated over 85,000 patients on treatment. Early warning indicator (EWI) reports can help to minimize the risk of emerging drug resistance. Methods Data collected during the routine quarterly supervision of 103 public sector sites was used to compile the first EWI report for HIV drug resistance (HIVDR) in Malawi, reflecting outcomes for October to December 2006. Results All sites reach the World Health Organization (WHO) targets for prescribing practices and drug supply continuity. The target for adherence was achieved by 85% of sites and 84% achieved the target for minimizing treatment defaults; however, less than half of all sites reach the WHO target for patient retention. Conclusions These results emphasize the importance of defaulter tracing and initiating treatment earlier in the course of HIV infection. As part of a comprehensive HIVDR monitoring programme, the Ministry of Health plans for on-going tracking of these indicators, as well as special data collection from the private sector. Plans are also underway to gather information on other recommended indicators that are not collected during routine supervision.
Prognostic factors for virological response in antiretroviral therapy-naive patients in the MONARK Trial randomized to ritonavir-boosted lopinavir alone
Authors: Flandre Philippe , Delaugerre Constance , Ghosn Jade , Chaix Marie Laure , Horban Andrzej , Girard Pierre-Marie , Gladysz Andrzej , Cohen-Codar Isabelle , Van Philippe Ngo , Taburet Anne-Marie , Rouzioux Christine , Delfraissy Jean-François 
Published: April 2022

Background MONARK is a pilot randomized trial comparing the safety and efficacy of lopinavir/ritonavir (LPV/r) monotherapy to a standard triple-drug regimen as initial therapy. The primary endpoint was virological response (VR) defined as viral load (VL)<400 copies/ml at week 24 and VL<50 copies/ml at week 48. The objective of this study was to determine prognostic factors of VR in patients receiving LPV/r monotherapy. Methods Baseline characteristics, including demographics, HIV type-1 (HIV-1) subtype (B versus non-B), early VR up to week 4, LPV trough concentrations and compliance were investigated as prognostic factors for VR in patients receiving LPV/r monotherapy. Logistic regression was used to search for variables significantly associated with the occurrence of VR. Results VR was achieved in 53 out of 83 patients randomized to the LPV/r arm. The on-treatment analysis, using a multivariate model, indicated that having VL<400 copies/ml at week 4 and harbouring HIV-1 subtype B were independently associated with an increased probability of VR. No difference in early VL reduction was evidenced between patients harbouring B or non-B subtypes. The latter patients had more difficulty in adherence to therapy than the former patients. The intention-to-treat analysis showed similar results. Conclusions HIV-1 RNA measured at baseline or at week 4 and HIV-1 subtype (B versus non-B) were independent predictive factors of VR in patients starting therapy with LPV/r alone. Although based on a small sample size, results of this study showed that adherence to therapy is lower in patients harbouring non-B subtypes and appears to be a key factor of VR in the context of protease inhibitor monotherapy.