bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of emphysema progression in HIV‐positive patients
Authors: Guaraldi Giovanni , Santoro Antonella , Besutti Giulia , Scaglioni Riccardo , Ligabue Guido , Zona Stefano , Man Paul , Sin Don , Leipsic Jonathon , Mussini Cristina 
Published: November 2014

IntroductionThe aim of the study was to find factors associated with emphysema progression (EP), assessed on sequential thoracic CT scans, in a large cohort of HIV‐positive patients.Materials and MethodsThis was an observational, prospective study of 448 consecutive HIV‐positive patients on antiretroviral therapy who underwent two sequential ECG‐gated coronary artery calcium scoring CT scans. Images were reviewed by three radiologists by consensus to assess lung emphysema using a visual semi‐quantitative score (0 to 4) for each of six lobes. EP was defined as an increase in emphysema score. Heavy smoking habit was defined as a self‐reported number of cigarettes per day smoked greater than 10. Immune reconstitution was defined as the change in CD4 cell count between first CT scan and CD4 nadir and it was divided into tertiles. Progressors and non‐progressors were compared using X2‐test for categorical variables and T‐test of Mann–Whitney U test for continuous variables where appropriate. Factors independently associated with EP were explored using multivariable logistic regression analyses. A p‐value <.05 was considered statistically significant.ResultsThe mean age of the included patients was 47,9±7,7 years, 24,1% of them were females and 39,3% were smokers. The median interval between the two CT scans was 2,4 years (interquartile range 0,69–5,9 years). EP was significantly associated with HIV‐infection duration (p=0,056), smoking (p=0,007) and in particular heavy smoking habit (p=0,015) and time interval between the two scans (p=0,021), while the highest tertile of immune reconstitution was borderline in significance (p=0,075). Age and sex were not significantly related to EP and were not included in further analyses. HIV infection duration (OR=1,01; p=0,013), time interval between the two scans (OR=1,51; p=0,032) and heavy smoking habit (OR=3,36; p=0,041) remained independently associated with EP in multivariate analysis.ConclusionsIn this large cohort of HIV positive patients on antiretroviral therapy, HIV infection duration, time between CT scans and continued heavy cigarette smoking were independently associated with EP.
More safer sex intervention needed for HIV‐positive MSM with higher education level for prevention of sexually transmitted hepatitis C
Authors: Wai Chi Lin Ada , Hing Wong Ka , Chan Kenny 
Published: November 2014

IntroductionThe epidemiology of hepatitis C virus (HCV) infections in Chinese HIV‐infected men who have sex with men (MSM) remains obscure. More data is required to understand the epidemic and set up preventive strategy.Materials and MethodsBaseline and annual testing of anti‐HCV was in place for all HIV‐infected MSM in the largest HIV clinic in Hong Kong. Logistic regression was used to compare those with HCV seroconversion (seroconverters) with those remained tested anti‐HCV negative (non‐seroconverters) to identify factors associated with incident HCV.ResultsFrom 1999 to 2013, 1311 patients were tested for anti‐HCV seroconversion, contributing to 6295 patient‐years of observation. Fourteen (1.1%) patients seroconverted, with genotype 3 being most commonly detected. The overall incidence rate of HCV infection was 0.22 per 100 patient‐years (PY) in the cohort. The incidence rate increased from 0.13 per 100PY before 2002 to 0.19 per 100PY in 2002–2007 and 0.47 per 100PY in 2008–2013. All the seroconverters were Chinese, with median age of anti‐HCV seroconversion at 38 years (range: 28–53 years). None of them were injecting drug users. As compared with the non‐seroconverters, seroconverters were of higher education level (85.7% vs 50.7% tertiary education or above, OR 5.28, p=0.021) and had prior history of sexually transmitted infection (92.9% vs 60.9%, OR 8.34, p=0.041). More seroconverters were found to have history of syphilis infection (57.1% vs 37.2%, p=0.134) but the difference was not statistically significant. Baseline CD4 count and HIV viral load, proportion on antiretroviral therapy and duration of antiretroviral therapy were not different between two groups.ConclusionsThe incidence of HCV has been increasing among HIV‐infected MSM non‐injecting drug users in Hong Kong. More education and intervention on safer sex is required to be targeted on those with higher education level.
Clinical and socio‐demographic predictors for virologic failure in rural Southern Africa: preliminary findings from CART‐1
Authors: Daniel Labhardt Niklaus , Bader Joëlle , Ramoeletsi Mojakisane , Kamele Mashaete , Ismael Lejone Thabo , Cheleboi Molisana , Motlatsi Mokete M. , Ehmer Jochen , Faturyiele Olatunbosun , Puga Daniel , Klimkait Thomas 
Published: November 2014

IntroductionIn 2013, the World Health Organization (WHO) recommended scaling up of routine viral load (VL) monitoring for patients on antiretroviral therapy (ART) in resource‐limited settings [1]. During the transition phase from no VL‐testing at all to routine VL‐monitoring, targeted VL for groups at particular risk of virologic failure (VF) may be an option [2]. We present socio‐demographic and clinical risk factors for VF in a cohort in rural Lesotho with no access to VL prior to the study.Materials and MethodsData derive from a cross‐sectional study providing multi‐disease screening as well as VL testing to adult patients (≥16 years old) on first‐line ART ≥6 months [3]. VF was defined as VL≥1000 copies/mL. Assessed potential predictors of VF were: (1) socio‐demographic (sex, age, wealth‐quintile, education, employment status, disclosure of HIV status to environment, travel‐time to facility); (2) treatment history (history of treatment interruption >2 days, previous drug substitution within first‐line ART, time on ART, ART‐base and ‐backbone); (3) adherence (pill count) and (4) clinical (clinical or immunological failure as defined by WHO guidelines [1], presence of papular pruritic eruption (PPE)). All variables with association to VF in univariate analysis were included in a multivariate logistic regression reporting adjusted Odds ratios (aOR).ResultsData from 1,488 patients were analyzed. Overall VF‐prevalence was 6.9% (95% CI 5.7–8.3). In univariate analysis, the following were associated with VF: age <30, lower wealth‐quintile, no primary education, history of treatment interruption, nevirapine‐base, zidovudine‐backbone, history of drug substitution, travel‐time to clinic ≥2 hours, disclosure of HIV status to <5 persons, clinical failure, presence of PPE and immunological failure. In multivariate analysis, 6 out of the above 12 variables were independent predictors: age <30 years (aOR: 2.4; 95% CI 1.1–5.3, p=0.029), history of treatment interruption (2.5; 1.3–4.7, p=0.005), PPE (6.9; 2.5–18.9, p<0.001), immunological failure (11.5; 5.7–23.2, p<0.001), history of drug substitution (1.9; 1.0–3.7, p=0.043), disclosure of HIV status to <5 persons (1.8; 1.1–3.1, p=0.03).ConclusionIn this cohort in rural Lesotho, several socio‐demographic and clinical predictors were associated with VF. Particularly age <30 years, history of treatment interruption, PPE and immunological failure were strongly associated with VF. These patients may be prioritized for targeted VL‐testing.
Longitudinal comparison of HIV‐1 plasma viral load and cellular proviral load
Authors: Schweitzer Finja , Mikkola Visa , Timmen‐Wego Monika , Jensen Björn , Fätkenheuer Gerd , Kaiser Rolf 
Published: November 2014

IntroductionThe goal of antiretroviral treatment (ART) in HIV‐1 infection is the permanent suppression of plasma viral load (pVL) below the currently existing limit of detection of 50 copies/mL (DAIG HIV‐therapy guidelines). Therefore, treatment effectiveness is based on pVL. pVL measurements however do not give any information about the viral reservoir in peripheral blood mononuclear cells (PBMCs). Therefore, the proviral DNA of HIV‐1 could be a useful marker for the investigation of viral reservoirs and monitoring ART in patients showing undetectable pVL.Materials and MethodsSeventy‐seven treatment‐experienced HIV‐1 infected patients with pVL <50 copies/mL were randomly selected. pVL and proviral DNA load were measured using the Roche COBAS TaqMan HIV‐1 v2.0 assay. Additionally, CD4+ cell count per mL and the total white blood cell (wbc) count per mL were determined for each patient. Follow‐up data were collected 24 weeks after the time point of the first measurement. Proviral DNA load per mL, CD4+ cell count per mL as well as wbc count per mL were observed over time and differences were estimated using the Mann–Whitney U test. Additionally, correlations between the clinical parameters were analyzed using the two‐sided Pearson correlation analysis.ResultsOut of the 77 patients, 38 show a significant increase in proviral load per mL over time (p=0,001), whereas 39 patients show a significant decrease (p=0,001). No differences became visible in the CD4+ cell count per mL comparing week 0 and week 24 data. Thirty five patients show a significant increase in wbc count per mL over time (p<0,001), while 42 patients show a significant decrease (p<0,001). A significant correlation of increasing proviral load per mL and wbc count per mL for data of the first (p<0.001) and the second measurement (p<0.001) can be detected, while there are no correlations found between proviral load per mL and CD4+ cell count per mL.ConclusionsOur data show that the presence of viral reservoirs in other cell types and not only CD4+ cells is most probable. HIV‐1 proviral DNA seems to be an interesting marker in patients with undetectable pVL and allows the assessment of replication under ART. Nevertheless, further longitudinal studies are needed to assess the usefulness and the clinical significance of this marker.
Accurate episomal HIV 2‐LTR circles quantification using optimized DNA isolation and droplet digital PCR
Authors: Malatinkova Eva , Kiselinova Maja , Bonczkowski Pawel , Trypsteen Wim , Messiaen Peter , Vermeire Jolien , Verhasselt Bruno , Vervisch Karen , Vandekerckhove Linos , De Spiegelaere Ward 
Published: November 2014

IntroductionIn HIV‐infected patients on combination antiretroviral therapy (cART), the detection of episomal HIV 2‐LTR circles is a potential marker for ongoing viral replication. Quantification of 2‐LTR circles is based on quantitative PCR or more recently on digital PCR assessment, but is hampered due to its low abundance. Sample pre‐PCR processing is a critical step for 2‐LTR circles quantification, which has not yet been sufficiently evaluated in patient derived samples.Materials and MethodsWe compared two sample processing procedures to more accurately quantify 2‐LTR circles using droplet digital PCR (ddPCR). Episomal HIV 2‐LTR circles were either isolated by genomic DNA isolation or by a modified plasmid DNA isolation, to separate the small episomal circular DNA from chromosomal DNA. This was performed in a dilution series of HIV‐infected cells and HIV‐1 infected patient derived samples (n=59). Samples for the plasmid DNA isolation method were spiked with an internal control plasmid.ResultsGenomic DNA isolation enables robust 2‐LTR circles quantification. However, in the lower ranges of detection, PCR inhibition caused by high genomic DNA load substantially limits the amount of sample input and this impacts sensitivity and accuracy. Moreover, total genomic DNA isolation resulted in a lower recovery of 2‐LTR templates per isolate, further reducing its sensitivity. The modified plasmid DNA isolation with a spiked reference for normalization was more accurate in these low ranges compared to genomic DNA isolation. A linear correlation of both methods was observed in the dilution series (R2=0.974) and in the patient derived samples with 2‐LTR numbers above 10 copies per million peripheral blood mononuclear cells (PBMCs), (R2=0.671). Furthermore, Bland–Altman analysis revealed an average agreement between the methods within the 27 samples in which 2‐LTR circles were detectable with both methods (bias: 0.3875±1.2657 log10).Conclusions2‐LTR circles quantification in HIV‐infected patients proved to be more accurate with a modified plasmid DNA isolation procedure compared to total genomic DNA isolation. This method enables the processing of more blood cells, thus enhancing quantification accuracy and sensitivity. An improved quantification of 2‐LTR circles will contribute to the better understanding of ongoing replication in the HIV reservoir of patients on cART.
Outcomes of initial antiretroviral treatment (ART) among recently diagnosed HIV patients in HIV‐TR cohort, 2011–2012
Authors: Korten Volkan , Gökengin Deniz , Fincanci Muzaffer , Yildirmak Taner , Uzun Kes Nuray , Taşdelen Fişgin Nuriye , Inan Dilara , Eraksoy Haluk , Akalin Halis , Kaptan Figen 
Published: November 2014

IntroductionHIV‐TR is a recently established (2012) multicentre cohort in Turkey. The aim of this study is to analyze epidemiological, immunologic and virologic data of recently diagnosed HIV patients.Materials and MethodsEpidemiologic, clinical and laboratory data of all patients diagnosed in 2011 and 2012 were recorded by a web‐based data collection system, retrospectively.ResultsA total of 693 patients (561 male, 132 female) at 24 sites were enrolled. The median age at first presentation for HIV care was 36. The proportion of patients presenting with advanced HIV disease (CD4 count<200/mm3 or presenting with an AIDS‐defining event) was 30.6%; and 52.4% of patients were late presenters (CD4 count<350/mm3 or presenting with an AIDS‐defining event). Median CD4 counts at presentation and before treatment were 344 (IQR: 175–540) and 295 (IQR: 150–430), respectively. Pretreatment CD4 count was >500 copies/mL in 18.5% of patients. Of 531 patients receiving ART, initial combinations consist of tenofovir/emtricitabine (TDF/FTC) plus efavirenz (EFV) in 48.2% and TDF/FTC plus lopinavir/ritonavir (LPV/r) in 37.5% and other combinations in 14.3% of the patients. Pre‐treatment HIV‐RNA was over 100.000 copies/mL in 52.3% of patients. At Weeks 24 and 48, HIV‐RNA were<50 copies/mL in 63,4% of 385 patients and 82% of 311 patients reported to be still on ART and had a viral load measurement, respectively. Median pretreatment CD4 count was lower for TDF/FTC+LPV/r recipients than TDF/FTC+EFV recipients (250 vs 316) (p<0.05). The median increase from baseline CD4 cell count was 230 in TDF/FTC+LPV/r group, 193 in TDF/FTC+EFV group and 216 among all treated patients. Of 531 patients receiving ART, 11 had died and 19 were lost to follow‐up.ConclusionDespite 52.4% of recently diagnosed patients were late presenters; a high rate of virologic suppression was achieved in HIV‐TR Cohort. A national HIV testing strategy targeting subpopulations with higher risk is urgently needed.
Structural‐equation‐modelling of the tropism impact on achieving viral suppression within six months in naïve HIV patients
Authors: Mengoli Carlo , Andreis Samantha , Scaggiante Renzo , Cruciani Mario , Bosco Oliviero , Ferretto Roberto , Leone D. , Maffongelli Gaetano , Basso Monica , Sarmati Loredana , Andreoni Massimo , Palù Giorgio , Giuseppe Parisi Saverio 
Published: November 2014

IntroductionAim of the study was to evaluate the relevance of baseline (BL) plasma tropism of HIV on the achievement of a viral suppression within six months of antiviral therapy (ARV) in naïve patients by a structural‐equation‐modelling.Materials and MethodsTwo‐hundred and twenty‐seven patients were enrolled; viral tropism on plasma was determined at baseline (BL) by sequencing and interpretation by genotopheno algorithm. Booster atazanavir or lopinavir, or efavirenz or nevirapine were used, in combination with either abacavir/lamivudine or tenofovir‐emtricitabine.ResultsX4‐tropism correlate negatively with CD4 cell count at BL and follow‐up (FU), and CD4 correlate negatively with BL‐plasma viremia (PLV). BL‐PLV correlate positively with FU‐PLV. We have developed the hypothesis that the variables BL‐CD4 and BL‐PLV represent a mediators chain among X4‐tropism and outcome of plasma viraemia at six months. This model, after structural‐equation‐modelling (SEM, Stata13), is shown in Figure 1. The indirect effect of X4‐tropism on Fup‐PLV is significant (p<0.01) but about 10 fold lower than the direct effect by BL‐PLV. X4‐tropism also has a direct negative effect on BL‐CD4 (p<0.001) and an indirect positive effect on BL‐PLV (p<0.001), irrespective of the drug regimen. Path model explaining direct and mediated effects of “tro (tropism),” “gender,” “age,” “cd0 (BL‐CD4)” and “lrna0 (BL‐PLV)” on the final outcome (“lrna1‐Fup‐PLV),” where “tro,” “gender,” and “age” are exogenous, cd0 and lrna0 are endogenous (mediators). Numbers on the arrows indicate direct effects. Circles indicate residuals related to endogenous/dependent variables; numbers near to circles are the corresponding variances.ConclusionsThis model shows the relevance of BL‐tropism on the outcome of plasma viraemia in naïve patients after six months of therapy, irrespective of drug regimen used.
Plasma HIV‐1 tropism and risk of short‐term clinical progression to AIDS or death
Authors: Casadellà Fontdevila Maria , Cozzi‐Lepri Alessandro , Phillips Andrew , Noguera Julian Marc , Bickel Marcus , Sedlacek Dalibor , Kronborg Gitte , Lazzarin Adriano , Zilmer Kai , Clotet Bonaventura , Lundgren Jens D , Paredes Roger 
Published: November 2014

IntroductionIt is uncertain if plasma HIV‐1 tropism is an independent predictor of short‐term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case‐control study within EuroSIDA to assess this question amongst people with current HIV RNA level >1000 copies/mL, including both people on ART and those ART naïve.MethodsPeople with an AIDS diagnosis or who died from any causes for whom there was a stored plasma sample with HIV‐1 RNA (VL)≥1,000 copies/mL available in the time window of 3–12 months prior to the event were identified. At least one control was selected for each case matched for age, VL and HCV status at the time of sampling. Controls were event‐free after a matched duration of time from the date of sampling. Plasma HIV tropism was estimated using 454 and population sequencing (PS). Non‐R5 HIV was defined as: (a) ≥2% of sequences with a Geno2Pheno (G2P) FPR≤3.75% by 454, and (b) a G2P FPR≤10% by PS. We also compared CD4 slopes over the 12 months following the date of sampling using a linear mixed model with random intercept according to HIV tropism and ART status.ResultsThe study included 266 subjects, 100 cases and 166 controls, with sample taken on average in 2006; 23% and 24% had non‐R5 HIV by 454 and PS respectively. There were 19% women, 25% MSM, 92% Caucasians, 22% HCV+. At the time of sampling, 26% were ART‐naïve, 25% had started but were off ART and 49% were receiving ART. The median age, CD4 and viral load was 41 years, 350 cells/mm3 and 4.81 log c/mL, respectively. Baseline characteristics were well balanced by tropism. Factors independently associated with clinical progression or death were female gender (OR=2.12; 95% CI=1.04, 4.36; p=0.038), CD4+ count (OR=0.90 per 100 cells/mm3 higher; 95% CI 0.80, 1.00; p=0.058), being on ART (OR=2.72; 95% CI 1.15, 6.41; p=0.022) and calendar year of sample (OR=0.84 per more recent year; 95% CI=0.77, 0.91; p<0.001). Baseline plasma tropism was not an independent risk factor for clinical progression or death by either 454 or PS. No significant interaction was observed between tropism and ART status. There were no significant differences in the CD4+ slope within or between tropism groups.ConclusionsPlasma HIV‐1 tropism does not appear to add to the ability of CD4 count and viral load to predict the short term risk of AIDS and death outcomes, even with 454 sequencing.
Characteristics of late presentation of HIV infection in MSM and heterosexual adults in Portugal 2011–2013
Authors: Shivaji Tara , Diniz Antonio , Cortes‐Martins Helena 
Published: November 2014

IntroductionIt is estimated that over half of newly diagnosed HIV infections in Europe present late. An HIV positive individual presenting late to care represents a missed opportunity to benefit from treatment, increasing the risk of morbidity and mortality at an individual level, and onward disease transmission at population level. Reducing late presentation is a strategic priority of the Portuguese HIV/AIDS program. We set out to describe the characteristics of late presentation in the two largest transmission risk groups currently in Portugal to inform HIV prevention and treatment.MethodsWe extracted details of all notified cases from individuals over 15 years with a laboratory confirmed HIV diagnosis made between January 2011 and December 2013 from the Portuguese HIV surveillance database and selected cases from heterosexuals and men who have sex with men (MSM). We defined late presentation as an initial CD4 count <350 cells/mm3 or presence of AIDS‐defining disease at time of HIV diagnosis. We calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) for characteristics associated with late presentation in separate logistic regression for heterosexuals and MSM.ResultsOf 4219 HIV positive cases notified, 2589 (61%) were heterosexuals and 1220 (29%) were MSM. A total of 1586 (38%) cases presented late of which 1037 (40%) were heterosexual and 328 (27%) were MSM. The median age at late presentation was 40 in heterosexual women, 46 in heterosexual men and 35 in MSM. A total of 1446 (55%) of heterosexual HIV positive adults were unaware of having had a high risk sexual contact. Late presentation among heterosexuals was associated with being male (aOR=1.58 95% CI 1.29–1.93), not knowing a partners’ HIV status (OR=1.59 95% CI 1.35–1.87) and age, increasing the odds of late presentation by a factor of 1.02 per year (95% CI 1.01–1.03). Among MSM, only age was associated with late presentation, increasing by 1.04 (95% CI 1.03–1.05) per year.ConclusionsPortuguese HIV prevention programs need to increase the risk awareness of heterosexuals, particularly men, to reduce missed opportunities for early diagnosis. As half of all cases presenting late are aged 40 and over, we recommend that general HIV outreach services and specialist services for MSM review their accessibility and acceptability to both middle and older‐aged clients.