bluuebunny/crossref_metadata_2025_split huggingface dataset:
A clinically useful risk‐score for chronic kidney disease in HIV infection
Authors: Mocroft Amanda , Lundgren Jens , Ross Michael , Law Matthew , Reiss Peter , Kirk Ole , Smith Colette , Wentworth Debbie , Heuhaus Jacquie , Fux Christophe , Moranne Olivier , Morlat Phillipe , Johnson Margaret , Ryom Lene ,   on behalf of the Data on Adverse Events (D:A:D) study group,the Royal Free Hospital Clinic Cohort and the INSIGHT study group
Published: November 2014

IntroductionDevelopment of a simple, widely applicable risk score for chronic kidney disease (CKD) allows comparisons of risks or benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen.Materials and MethodsA total of 18,055 HIV‐positive persons from the Data on Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs) >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73 m2 after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months apart) eGFR <60. Poisson regression was used to develop a score predicting low (<0 points), medium (1–4 points) and high (>5 points) risk of developing CKD. Increased incidence of CKD associated with starting ARVs was modelled by including ARVs as time‐updated variables. The risk score was externally validated on two independent cohorts.ResultsA total of 641 persons developed CKD during 103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7–6.7). Older age, intravenous drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (Figure 1). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6–1.0), 5.6 (95% CI 4.5–6.7) and 37.4 (95% CI 34.0–40.7) (Figure 1). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90–0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.1–6.1) and 2013 persons from the control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5–5.1). External validation showed consistent CKD rates across risk groups (Figure 2).InterpretationTraditional and HIV‐related risk factors were predictive of CKD; all are routinely available, making the risk score easy to incorporate into clinical practise and of direct relevance for clinical decision making. NNTH in persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and alternative ARVs may be more appropriate.
Effectiveness of a team intervention in reducing modifiable cardiovascular disease risk in HIV‐infected subjects on antiretroviral therapy
Authors: Bloch Mark , Jayewardene Avindra , Vincent Trina , Linton Natalie , Quan Dick , Gowers Andrew 
Published: November 2014

IntroductionThe increasing age, higher modifiable and inherent cardiovascular disease (CVD) risk of HIV‐infected patients [1] necessitates improved approaches to reducing co‐morbidities. We aimed to assess the effectiveness of a team intervention in reducing modifiable CVD risk.Materials and MethodsHIV‐infected patients ≥50 years attending a large HIV caseload primary‐care practice, who were virologically suppressed on antiretroviral therapy (ART), with moderate or severe 10‐year CVD Framingham risk (≥10%) were recruited for this prospective case‐control study. Intervention participants were provided a team approach to care, which involved treatment by study doctors for lipid, hypertension and ART management, and monthly review by a team of research nurses and dieticians for smoking cessation, exercise and dietary advice over 12 months. Controls were matched on age and smoking status, and were given standard of care (SOC) by non‐study doctors. Outcomes included CVD risk factors, body composition and CVD risk assessment, including Framingham 10‐yr risk [2] and D:A:D 5‐year estimated risk of coronary heart disease (CHD) [3]. Repeated measures analysis of variance was used to examine pre‐ and post‐intervention differences, with p‐values used to assess time and main effects of approach to care (Intervention, SOC).ResultsA total of 33 patients completed the intervention, with 33 controls (58.0±6.8 and 59.1±6.9 years, respectively). Smoking cessation occurred in 25% cases versus nil controls. There was a significant change in CVD risk between intervention and control groups, in both Framingham scores (time and group×time interaction) and D:A:D scores (group×time interaction only) (Table 1). There was also a significant difference in change in total cholesterol over the study period (time and group×time interaction). Body composition was only measured in intervention patients, with a significant loss in % body fat observed in pre‐ and post‐intervention.ConclusionsTeam intervention was significantly more effective than standard of care in reducing CVD risk in HIV‐infected patients on ART. A team approach to care may be an important component of reducing CVD risk in this population.
Early changes in coagulation but not inflammatory biomarkers under intermittent ART: the randomized ANRS 106 WINDOW trial
Authors: Gallien Sébastien , Charreau Isabelle , Fonsart Julien , Mourah Samia , Kalidi Issa , Delobel Pierre , Marchou Bruno , Aboulker Jean‐Pierre , Molina Jean‐Michel 
Published: November 2014

IntroductionIn the SMART trial, baseline plasma hsCRP, IL6 and D‐dimer levels were strongly correlated to all‐cause mortality. A case‐control study has shown an increase of IL‐6 and D‐dimer levels after one month of antiretroviral therapy (ART) interruption, which was correlated to viral load. Restarting ART was associated to a decrease in D‐dimer but not IL‐6 or hsCRP levels. We assessed biomarkers levels up to 96 weeks in ART‐experienced adults with plasma HIV RNA levels <400 c/mL randomized in the ANRS 106 WINDOW trial to intermittent ART (IT: six cycles of eight weeks of ART interruption followed by eight weeks of ART) versus continuous treatment (CT).MethodsStored plasma for 160 participants (80 IT and 80 CT), matched by age, sex and CDC classification, were analyzed blinded for IL‐6, sCD‐14, hsCRP and D‐dimer levels at baseline, week 8 (IT group only), week 16 and week 96. Lower levels of detection for IL‐6, sCD14, hsCRP and D‐Dimer were 1.5 pg/mL, 250 ng/mL, 0.03 µg/mL and 0.21 µg/mL, respectively. The primary objective was to compare changes in IL‐6, hsCRP, sCD14 and D‐dimer plasma levels from baseline to week 8, 16 and 96 in the IT and CT arms. Biomarkers levels were log10 transformed prior to analysis.ResultsAt baseline, patients were mostly men (86%), with a median age of 40 years, a CD4+ T‐cell count of 768/mm3, have received a median of 4.7 years of ART and 85% had HIV RNA <50 c/mL. Proportion of patients with plasma HIV RNA levels<400 c/mL were 6% and 99%, 81% and 97%, 86% and 92% at weeks 8, 16 and 96 in the IT and CT arms, respectively. Plasma biomarkers levels are shown in the Table 1.Compared to baseline, D‐dimer levels significantly increased 8 weeks after ART interruption in the IT arm (+23% fold change, 95% CI +9% to +39%) but reverted to baseline levels at week 16 and remained unchanged at week 96. There was no significant change from baseline in the other biomarker levels in the IT arm. Similarly, no significant change from baseline in biomarker levels was seen in the CT arm up to 96 weeks.ConclusionCoagulation and inflammatory biomarkers levels remained stable over 96 weeks in well‐suppressed HIV‐infected patient on ART. Following ART interruption there was a significant increase in D‐dimer but not in inflammatory biomarkers levels. This increase was reversed upon reintroduction of ART. These data suggest that ART interruption increases coagulation rather than inflammatory biomarkers.
Changes in lipid levels after 48 weeks of dual versus triple therapy observed in the GARDEL study
Authors: Cahn Pedro , Andrade Villanueva Jaime , Arribas Jose , Gatell Jose , Lama Javier , Norton Michel , Patterson Patricia , Sierra Madero Juan , Sued Omar , Ines Figueroa Maria , Jose Rolón Maria 
Published: November 2014

IntroductionTreatment with ritonavir‐boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study.Materials and MethodsThe GARDEL study compared the efficacy and safety of a dual therapy (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT) with LPV/r 400/100 mg BID+3TC or FTC and a third investigator‐selected NRTI in fixed‐dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms.ResultsPatient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL‐C (94 mg/dL DT, 91 mg/dL TT) and HDL‐C (36 mg/dL DT, 35 mg/dL TT). Changes in total cholesterol, LDL‐C and HDL‐C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL). Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL‐C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC.ConclusionChanges in lipid parameters were observed in both arms. Albeit the increase was numerically higher for cholesterol (total and LDL‐C) in DT arm while TT arm had higher increases in TG; no difference was observed when week 48 values were compared with the NCEP ATP III goals for cardiovascular risk reduction [1]. So, the DT strategy, even missing the lipid‐lowering effect observed with tenofovir, does not seem to add significant risk to patients treated with this novel strategy.
The prevalence and predictive value of dipstick urine protein in HIV‐positive persons in Europe
Authors: Mocroft Amanda , Ryom Lene , Lapadula Giuseppe , Reiss Peter , Blaxhult Anders , Furrer Hansjakob , Kutsyna Galyna , Gatell Jose , Begovac Josep , Kirk Ole , Lundgren Jens ,   for EuroSIDA in EuroCoord
Published: November 2014

IntroductionProteinuria (PTU) is an important marker for the development and progression of renal disease, cardiovascular disease and death, but there is limited information about the prevalence and factors associated with confirmed PTU in predominantly white European HIV+ persons, especially in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2.Patients and methodsBaseline was defined as the first of two consecutive dipstick urine protein (DPU) measurements during prospective follow‐up >1/6/2011 (when systematic data collection began). PTU was defined as two consecutive DUP >1+ (>30 mg/dL) >3 months apart; persons with eGFR <60 at either DPU measurement were excluded. Logistic regression investigated factors associated with PTU.ResultsA total of 1,640 persons were included, participants were mainly white (n=1,517, 92.5%), male (n=1296, 79.0%) and men having sex with men (n=809; 49.3%). Median age at baseline was 45 (IQR 37–52 years), and CD4 was 570 (IQR 406–760/mm3). The median baseline date was 2/12 (IQR 11/11–6/12), and median eGFR was 99 (IQR 88–109 mL/min/1.73 m2). Sixty‐nine persons had PTU (4.2%, 95% CI 3.2–4.7%). Persons with diabetes had increased odds of PTU, as were those with a prior non‐AIDS [1] or AIDS event and those with prior exposure to indinavir. Among females, those with a normal eGFR (>90) and those with prior abacavir use had lower odds of PTU (Figure 1).There was no significant association between past or current use of tenofovir, lopinavir, atazanvir (boosted or unboosted) or any other boosted PI and PTU (p>0.2). During 688.2 person‐years of follow up (PYFU), three persons developed chronic kidney disease (CKD; confirmed [>3 months apart] eGFR<60); 2/685 (0.3%) without PTU and 1/38 (2.8%) with PTU (p=0.032). The crude incidence of CKD in those with baseline PTU and eGFR>60 was almost 10 times higher than in those without baseline PTU and eGFR>60 (rate ratio 9.61; 95% CI 0.87–105.9, p=0.065).ConclusionsOne in 25 persons with eGFR>60 had confirmed proteinuria at baseline. Factors associated with PTU were similar to those associated with CKD. The lack of association with antiretrovirals, particularly tenofovir, may be due to the cross‐sectional design of this study, and additional follow‐up is required to address progression to PTU in those without PTU at baseline. It may also suggest other markers are needed to capture the deteriorating renal function associated with antiretrovirals may be needed at higher eGFRs. Our findings suggest PTU is an early marker for impaired renal function.
Incremental cost per newly diagnosed HIV infection (NDHI): routine (RTS), targeted (TTS), and current clinical practice testing strategies (CPTS)
Authors: Gomez‐Ayerbe Cristina , Jesús Pérez Elías María , Muriel Alfonso , Pérez Elías Pilar , Cano Agustina , Diaz Alberto , Moreno Ana , Luis Casado Jose , Santos Cristina , Martinez‐Colubi María , Uranga Almudena , Dronda Fernando , Moreno Santiago 
Published: November 2014

IntroductionAlthough RTS as HIV Diagnosis was considered cost effectiveness [1], overall budget may be unaffordable for some countries. We explore Incremental cost per NDHI associated with different TS.Materials and MethodsFrom a health care perspective, using direct costs and Euros currency, we calculated budget and cost per NDHI of RTS (all patients were tested), TTS (Universal risk practices and clinical conditions‐RP&CC ‐ only positive were tested), and CPTS (Only patients physicians considered were tested). We considered DRIVE (Spanish acronym of HIV infection Rapid Diagnosis) study and clinical Practice outcomes. Population between 18–60 years, attending to a Hospital Emergency Room or to a Primary Care Center performed an HIV RP&CC questionnaire (Q) and an HIV rapid test (HIV RT). Unitary costs considered were: HIV RT, nurse, registry, transport and HIV confirmation when necessary, imputed to all population in RTS and CPTS and only in HIV RP&CC‐Q positive in TTS analysis, while HIV RP&CC‐Q costs were added to all population in TTS. Sensitivity analyses were performed with varying rates of NDHI and of positive HIV RP&CC‐Q population, and different RP&CC Q sensitivity (SE) to predict HIV infection.Results5,329 HIV RP&CC‐Q and HIV RT were performed to 49.64% women, median age 37 years old, 74.9% Spaniards. In DRIVE and CP, NDHI were 4.1‰, and 1.6‰, while HIV RP&CC‐Q was positive in 51.2%. HIV RP&CC‐Q SE was 100%. Overall budget employed in HIV testing was in RTS 43,503€, in TTS 24,472€ and in CPTS 5,032€. Cost per 1 NDHI was 1,977€, 1,112€ and 5,032€, respectively. A reduction in cost of 865€, favouring TTS vs. RTS, while an increased cost of 824€ in CPTS vs. RTS was obtained. Considering NDHI rate of 2.6‰ saving costs increased to 1379€ in TTS, while were reduced to 576€ if NDHI rate increases 6.2‰. Effect of RP&CC‐Q positivity rate was similar, if 25% saving costs were 1368€, while if 75% were reduced to 399€. Varying SE of RP&CC‐Q to 95%, 91% and 50% cost saving was 810€, 754€, and 208€, and number of MHI one, two and 11.ConclusionsIn DRIVE study Targeted TS with universal screening of RP&CC before an HIV rapid test is cost saving, without missing NDHI, with respect to Routine TS. Lower rates of HIV infection and RP&CC in the population, increase costs savings.
Hepatitis B virus (HBV) status of children born to HIV/HBV co‐infected women in a French hospital: a cross‐sectional study
Authors: Sellier Pierre , Schnepf Nathalie , Amarsy Rishma , Maylin Sarah , Coutellier Martin , Lopes Amanda , Mazeron Marie‐Christine , Flateau Clara , Morgand Marjolaine , Ciraru‐Vigneron Nicole , Berthe Aurore , Ricbourg Aude , Dolores‐Moreno Anne‐Marie , Simoneau Guy , Evans John , Souak Safia , Matheron Sophie , Mouly Stephane , Benifla Jean‐Louis , Simon François , Bergmann Jean‐François 
Published: November 2014

IntroductionHuman Immunodeficiency Virus (HIV) Mother‐To‐Child‐Transmission (MTCT) and prevention by combined antiretroviral therapy (cART) have been extensively studied. Hepatitis B Virus (HBV) MTCT from HIV/HBV co‐infected women and prevention by antiretroviral therapy with dual activity have been poorly studied. The aim of the study was to assess HBV MTCT from HIV/HBV co‐infected women in a developed country with a large access to cART.Materials and MethodsHIV/HBV co‐infected pregnant women attending the Obstetrics Department from 1st January 2000 to 1st January 2012 could be included in the study (NCT02044068). Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or vaccine to newborns was retrospectively recorded. We assessed HBV status of children at least as old as two years.ResultsForty nine (9.2%) from 530 HIV‐infected women followed in the hospital were HIV/HBV co‐infected. 34 (69.4%) had given birth to 57 children in the hospital. 13 of these women (22 children) were lost‐to‐follow‐up, 21 women (35 children) could be studied. Twenty six children (74.3%) had HBs Ab at a protective level, 22 of them had received immunoglobulin at birth; 24 had received a complete vaccine schedule during the first six months of life (with immunoglobulin in 21 cases). The women had been given lamivudine or tenofovir/emtricitabine during eight and nine pregnancies respectively. Eight children (22.8%) were tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%) had received immunoglobulin and a complete vaccine schedule; in two children, immunoglobulin was uncertain; in one child, the vaccine schedule was incomplete; in the last one, data about immunoglobulin and the vaccine schedule were lacking. The women had been given lamivudine or tenofovir/emtricitabine during five and two pregnancies respectively. One child had HBc Ab and HBs Ab, immunoglobulin was uncertain and the vaccine schedule was incomplete. The woman had been given lamivudine during the last trimester.ConclusionsThree quarters of the children were protected. HBs Ab were negative in more than a tenth of the children who had received immunoglobulin and a complete vaccine schedule, questioning on long‐term protection and underlining the need of control.
Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan
Authors: Su Yi‐Ching , Liu Wen‐Chun , Chang Lan‐Hsin , Wu Pei‐Ying , Luo Yu‐Zhen , Wu Cheng‐Hsin , Sun Hsin‐Yun , Chang Sui‐Yuan , Hung Chien‐Ching 
Published: November 2014

IntroductionThe incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource‐rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person‐years of follow‐up (PYFU) in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT) service at a University Hospital.MethodsBetween May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third‐generation enzyme immunoassay. A nested case‐control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013.ResultsDuring the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV‐negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76–4.94); the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05–4.51) in 2006–2009, to 3.33 per 1000 PYFU (95% CI, 0.86–5.80) in 2010–2011, to 4.94 per 1000 PYFU (95% CI, 0.99–8.99) in 2012–2013. In case‐control study, HCV seroconverters were more likely to have HIV‐infected partners, recent syphilis and a Rapid Plasma Reagin (RPR) titre of 4 or greater. In multivariate analysis, having HIV‐infected partners remained as the only independent associated factors with HCV seroconversion (AOR, 6.931; 95% CI, 1.064–45.163). Phylogenetic analysis revealed transmission pairs and clusters, with most clustered sequences derived from MSM.ConclusionsSimilar to the observation among HIV‐infected patients who are not IDUs, increasing trends of recent HCV infection also occur among the individuals who sought VCT services in Taiwan. Having HIV‐infected partners is independently associated with recent HCV seroconversion.
Analysis of transmitted drug resistance and HIV‐1 subtypes using dried serum spots of recently HIV‐infected individuals in 2013 in Germany
Authors: Andrea Hauser , Alexandra Hofmann , Claudia Santos‐Hoevener , Ruth Zimmermann , Osamah Hamouda , Norbert Bannert , Claudia Kuecherer 
Published: November 2014

IntroductionThe Robert Koch Institute (RKI) aimed to assess a molecular surveillance strategy based on filter‐dried serum spots (DSS) of all newly diagnosed HIV infections in Germany. In 2013, diagnostic laboratories sent DSS to the RKI representing 55% of the newly diagnosed HIV infections reported to the RKI (protection against infection act). DSS were first tested serologically to identify recently acquired infections (<140 days duration of infection); those classified as “recent infection” were processed for HIV‐1 genotyping. The aim of this study was to assess the level of TDR and the current HIV‐1 subtypes in the main HIV transmission group categories (TrGrpC) in 2013: men who have sex with men (MSM), women/men with heterosexual contacts (HET) and injecting drug users (IDUs).Materials and MethodsDSS were tested for recency of infection using the BED capture EIA. Viral RNA from “recent infections” was amplified by HIV‐1 group M generic pol‐RT‐PCR covering all resistance‐associated positions in the HIV‐1 protease (AS1‐99) and reverse transcriptase (AS1‐252) if viral loads were ≥6,500 copies/mL. PCR amplicons were sequenced (Sanger) to analyze genotypic resistance and the HIV‐1 subtype. Results were merged to data from the HIV report, i.e. the TrGrpC.ResultsIn 2013, 1027 DSS were classified as recent HIV infections (506 MSM, 118 HET, 31 IDUs, 6 others, 366 unknown). RNA was extracted from 703 recent cases and 389/503 samples with sufficient viral load were PCR‐positive. By June 2014, 276/389 samples were sequenced: TDR was identified in 13% (35/276) of the recent infections including single (PI, NRTI, NNRTI) and dual drug class resistant strains (NRTI/NNRTI; NNRTI/PI). 18% (51/276) of recent HIV‐1 infections were caused by non‐B subtypes (A1, C, CRF01_AE, CRF02_AG, D, F, G, URFs). TDR was observed at comparable levels in all TrGrpC. Proportions of non‐B infections were significantly higher in HET (78%; 14/18) and IDUs (60%; 3/5) compared to MSM (8%; 14/169) (p<0.01).ConclusionsThe proportion of TDR was similar but the proportion of HIV‐1 subtype non‐B infections was higher as previously described for Germany based on results from the German HIV‐1 Seroconverter Cohort [1,2]. This difference could be the result of a broadened inclusion of HET and IDUs due to the sampling method used making this study representative for molecular surveillance of HIV‐1 in Germany.