bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive value of prostate‐specific antigen for prostate cancer: a nested case‐control study in EuroSIDA
Authors: Shepherd Leah , Borges Álvaro Humberto , Ravn Lene , Harvey Richard , Viard Jean‐Paul , Bower Mark , Grulich Andrew , Silverberg Michael , De Wit Stephane , Kirk Ole , Lundgren Jens , Mocroft Amanda ,   on behalf of EuroSIDA in Eurocoord
Published: November 2014

IntroductionAlthough prostate cancer (PCa) incidence is lower in HIV+ men than in HIV− men, the usefulness of prostate‐specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV− men. We aimed to describe the kinetics and predictive value of PSA in HIV+ men.MethodsMen with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed models were used to describe kinetics.ResultsSixty‐one men were included with a median six (IQR 2–9) years follow‐up. Time between last sample and PCa was seven (4–11) months. Cases and controls were well matched at first sample, with a median age of 51 (IQR 48–57) and CD4 of 437 (243–610) cells/mm3. Median tPSA [2.8 (IQR: 1.6–4.6) and 0.8 (0.5–1.2) µg/L] and fPSA [0.4 (0.2–0.8) and 0.3 (0.2–0.4) µg/L] levels were higher in cases than controls at first sample. Both tPSA and fPSA increased significantly over time in cases (Figure 1), to a median at last sample of 6.1 (4.7–9.5) and 0.9 (0.6–1.3) µg/L, respectively, but were stable in controls, with a median at last sample of 0.8 (0.5–1.4) and 0.2 (0.2–0.4) µg/L (Figure). Higher levels of tPSA and fPSA were associated with higher odds of PCa at first sample [OR for 2‐fold higher 4.7 (CI: 1.7–12.9) and 5.4 (1.7–17.4)]. Elevated tPSA values in cases were detectable ≥5 years before PCa (p<0.01). Testosterone [overall median 19.4 (IQR 15.3–23.9) nmol/L at first sample) and SHBG [50.0 (34.0–66.0) nmol/L] levels were similar in cases and controls at first and last sample (all p>0.7). The most informative predictor of PCa was tPSA (AUC=0.9), followed by fPSA (0.8). Testosterone (AUC = 0.5) and SHBG (0.5) were poor predictors of PCa. Overall, tPSA level >4 µg/L had 99% specificity and 37% sensitivity. Performance was best in the year prior to PCa (specificity: 99%, sensitivity: 88%).ConclusionsPSA was highly predictive of PCa in HIV+ men. Our results indicate that PSA screening in HIV+ men may be useful, and further work is needed to identify potentially age‐related cut‐offs to maximize sensitivity and specificity to identify those for further evaluation at early stages of PCa.
Gender differences in HIV‐positive persons in use of cardiovascular disease‐related interventions: D:A:D study
Authors: Hatleberg Camilla Ingrid , Ryom Lene , El‐Sadr Wafaa , Mocroft Amanda , Reiss Peter , de Wit Stephan , Dabis Francois , Pradier Christian , d'Arminio Monforte Antonella , Rickenbach Martin , Law Matthew , Lundgren Jens , Sabin Caroline 
Published: November 2014

IntroductionThere is a lack of data on potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) in HIV‐positive individuals. We investigated whether such differences exist in the D:A:D study.Materials and MethodsFollow‐up was from 01/02/99 until the earliest of death, 6 months after last visit or 01/02/13. Rates of initiation of lipid‐lowering drugs (LLDs), angiotensin‐converting enzyme inhibitors (ACEIs), anti‐hypertensives and receipt of invasive cardiovascular procedures (ICPs; bypass, angioplasty, endarterectomy) were calculated in those without a myocardial infarction (MI) or stroke at baseline, overall and in groups known to be at higher CVD risk: (i) age >50, (ii) total cholesterol >6.2 mmol/l, (iii) triglyceride >2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or (vii) predicted 10‐year CVD risk >10%. Poisson regression was used to assess whether rates of initiation were higher in men than women, after adjustment for these factors.ResultsAt enrolment, women (n=13,039; median (interquartile range) 34 (29–40) years) were younger than men (n=36,664, 39 (33–46) years, p=0.001), and were less likely to be current smokers (29% vs. 39%, p=0.0001), to have diabetes (2% vs. 3%, p=0.0001) or to have hypertension (7% vs. 11%, p=0.0001). Of 49,071 individuals without a MI/stroke at enrolment, 0.6% women vs. 2.1% men experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall, women received ICPs at a rate of 0.07/100 person‐years (PYRS) compared to 0.29/100 PYRS in men. Similarly, the rates of initiation of LLDs (1.28 vs. 2.46), anti‐hypertensives (1.11 vs. 1.38) and ACEIs (0.82 vs. 1.37) were all significantly lower in women than men (Table 1). As expected, initiation rates of each intervention were higher in the groups determined to be at moderate/high CVD risk; however, within each high‐risk group, initiation rates of most interventions (with the exception of anti‐hypertensives) were generally lower in women than men. These gender differences persisted after adjustment for potential confounders (Table 1).ConclusionUse of most CVD interventions was lower among women than men in the D:A:D study. Our findings suggest that actions should be taken to ensure that both men and women are monitored for CVD and, if eligible, receive appropriate CVD interventions.
Forty‐eight‐week efficacy and safety and early CNS tolerability of doravirine (MK‐1439), a novel NNRTI, with TDF/FTC in ART‐naive HIV‐positive patients
Authors: Gatell Josep M , Morales‐Ramirez Javier O , Hagins Debbie P , Thompson Melanie , Keikawus Arasteh , Hoffmann Christian , Rugina Sorin , Osiyemi Olayemi , Escoriu Simona , Dretler Robin , Harvey Charlotte , Xu Xia , Teppler Hedy 
Published: November 2014

IntroductionDoravirine (DOR) is an investigational NNRTI (aka MK‐1439) that retains activity against common NNRTI‐resistant mutants. We have previously reported the Part 1 results from a two‐part, randomized, double‐blind, Phase IIb study in ART‐naïve HIV‐1‐positive patients [1]. At doses of 25, 50, 100 and 200 mg qd, DOR plus open‐label tenofovir/emtricitabine (TDF/FTC) demonstrated potent antiretroviral activity comparable to EFV 600 mg qhs plus TDF/FTC and was generally well tolerated at week 24. DOR 100 mg was selected for use in patients continuing in Part 1 and those newly enrolled in Part 2.MethodsPatients receiving DOR 25, 50 or 200 mg in Part 1 were switched to 100 mg after dose selection. In Part 2, 132 additional patients were randomized 1:1 to DOR 100 mg qd or EFV 600 mg qhs (each with TDF/FTC). We present week 48 efficacy and safety results for all patients in Part 1, and early (week 8) CNS tolerability only for patients randomized to DOR 100 mg or to EFV in Parts 1 and 2 combined. The primary safety endpoint is the % of patients with pre‐specified CNS events (all causality) by week 8 for DOR 100 mg qd vs EFV (Parts 1 + 2 combined).ResultsPart 1 week 48 efficacy and safety results are shown below.The most common DR clinical AEs in the DOR and EFV groups, respectively, were abnormal dreams (10.2%; 9.5%), nausea (7.8%; 2.4%), fatigue (7.2%; 4.8%), diarrhoea (4.8%; 9.5%) and dizziness (3.0%; 23.8%), and were generally mild to moderate.Part 1 + 2 Week 8 CNS Event Analysis: One hundred thirty‐two patients were randomized in Part 2, 66 to DOR 100 mg and 66 to EFV. Combining Part 1 and 2, a total of 108 patients received DOR 100 mg and 108 received EFV. By week 8, at least one CNS AE was reported in 22.2% of the DOR group and 43.5% of the EFV group (p<0.001). The most common CNS AEs were dizziness (DOR 9.3%; EFV 27.8%), insomnia (6.5%; 2.8%), abnormal dreams (5.6%; 16.7%) and nightmares (5.6%; 8.3%).ConclusionsIn ART‐naïve, HIV‐1‐positive patients also receiving TDF/FTC, DOR 100 mg qd demonstrated potent antiretroviral activity and immunological effect at week 48 and was generally safe and well tolerated. Patients who received DOR 100 mg qd had significantly fewer treatment‐emergent CNS AEs by week 8 than those who received EFV.
HIV/AIDS mortality in a south east European country versus a west European country
Authors: Dragovic Gordana , Smith Colette , Jevtovic Djordje , Kusic Jovana , Salemovic Dubravka , Ranin Jovan 
Published: November 2014

IntroductionAntiretroviral (ARV) treatment available in low‐middle income countries differs as suggested in international HIV‐treatment guidelines. Thus, we compared ARV regimens introduced as a first‐line therapy, time of initiation, frequency of making combination antiretroviral therapy (cART) switches, frequency of viral and immunological monitoring and treatment outcome in south east European (SEE) country (i.e. HIV Centre in Belgrade, Serbia, (HCB)) and west European country (i.e. Royal Free Centre for HIV Medicine at the Royal Free Hospital London, UK (RFH)).Materials and MethodsARV naïve patients starting cART from 2003 to 2012 were included. Comparisons of the two cohorts were made using a chi‐square test or Fisher's exact test for categorical variables and a Mann‐Witney U test for continuous variables. Kaplan Meier survival curves were compared using the log rank test.ResultsOf 597 patients from HCB, 361 (61%) initiated cART with prior AIDS diagnosed, while 337 (19%) of 1763 patients from RFH. Average baseline CD4+ T cell counts were significantly lower in Serbia than in UK (177 cells/mm3 vs 238 cells/mm3). The total (mediana, IQR) CD4+ T cell count measurements in the first year of cART was 2 (1, 2) at the HCB, while it was statistically significant higher at the RFH 5 (3, 7), respectively (p<0.0001). At the RFH, it appeared that the cART switching is due to patient's preference or toxicity (46%), while the lack of supply and toxicity (37%) were the most important reasons for treatment change in HCB, within the same period of time (p<0.05). Mortality rates were higher at the HCB versus RFH (p<0.0001). After 12, 24 and 36 months of cART, 3%, 5% and 8% of patients died in HCB, whereas 2%, 3% and 4% of patients died in RFH, respectively (Figure 1).ConclusionsIn south European countries, as a consequence of low testing rate, ARV treatment is introduced at an advanced stage of disease, having a high mortality rate as a consequence. Switching within ARV drugs appears often due to lack of drug supplies and frequently drug‐related toxicity in south east Europe, while in the east European country due to patient's preferences and rarely due to drug‐related toxicity.
The effects of Maraviroc on liver fibrosis in HIV/HCV co‐infected patients
Authors: Ortega Gonzalez Enrique , Boix Vicente , Garcia Deltoro Miguel , Lopez Aldeguer Jose , Portilla Joaquin , Montero Marta , Ballester Belda Emilio , Abril Vicente , Gutierrez Felix , Minguez Carlos , Galindo Josefa , Benirto Concepcion , Garcia Rodriguez Magdalena , Giner Livia , Rubio Purificacion , Uso Jorge , Llerena Giovanna 
Published: November 2014

IntroductionThe fibrogenesis analysis in quimeric CCR1 and CCR5 mice revealed that CCR5 mediates its pro‐fibrogenic effects in hepatic cells and promoting stellate cells. The blockage of co‐receptors could preserve the progression of hepatic fibrosis in HIV/HCV co‐infected patients.ObjectiveTo evaluate the beneficial effects on hepatic fibrosis in HIV/HCV co‐infected patients that are on antiretroviral therapy (ART) with CCR5 co‐receptor antagonists.Method and materialsA multicentre, retrospective pilot study of the evaluation of hepatic fibrosis at mid‐ and long‐term by non‐invasive methods in a HIV/HCV co‐infected patients cohort in the Valencian Community (Spain) that received ART with a CCR5 co‐receptor antagonist. The cut‐off points of serum marker tests of hepatic fibrosis were: AST to Platelet Ratio Index (APRI)<0.5 (F0–F1); >1.5 F2; >2 Cirrhosis and Forns Index<4.2 excludes fibrosis; >6.9>F2 fibrosis. Inclusion criteria was established for HIV/HCV co‐infected patients on ART with CCR5 co‐receptor antagonists that had no previous history of interferon and ribavirin treatment or those who were null‐responders and received CCR5 co‐receptor antagonist treatment in the previous year. Patients with HBV infection were excluded.ResultsA total of 71 male patients (69%) were reported. A CD4 nadir <100 cells/uL was observed in 42% of patients and 62% (44/71) had a basal CD4 level >350 cells/uL. According to genotypes, 50% were G‐1a, 14% G‐1b, 11% G‐3 and 25% G‐4. The median duration of treatment with Maraviroc (MVC) was the following: 45% took it over a year, 41% over two years and 14% over three years. Before starting treatment with MVC, we observed an initial fibrosis of F0–F1 in 49% of patients, F2–F3 in 24% and F4 in 27%. The medium follow‐up was of 18.45 months. Progression to a higher fibrosis level was observed in five patients, 11 patients improved at least one stage and the others were stable over time. There were 38 patients taking MVC over two years, 27 patients in this group (59.38%) did not modify their fibrosis, 3 patients (11%) progressed and 8 (29.62%) showed regression of liver fibrosis in one stage.ConclusionsThe data above shows a benefit over fibrosis progression with MVC, expressed by fibrosis serum marker tests in HIV/HCV co‐infected patients with CCR5 tropism. The prolong treatment with MVC (over two years) has a better effect on liver fibrosis.
Bladder cancer in HIV‐infected adults: an emerging concern?
Authors: Chawki Sylvain , Ploussard Guillaume , Montlahuc Claire , Verine Jérome , Mongiat‐Artus Pierre , Desgrandchamps François , Molina Jean‐Michel 
Published: November 2014

IntroductionAs HIV‐infected patients get older more non‐AIDS‐related malignancies are to be seen. Cancer now represents almost one third of all causes of deaths among HIV‐infected patients [1]. Albeit bladder cancer is one of the most common malignancy worldwide [2], only 13 cases of bladder cancer in HIV‐infected patients have been reported in the literature so far [3].Materials and MethodsWe conducted a monocentric study in our hospital. We selected all patients who were previously admitted (from 1998 to 2013) in our hospital with diagnoses of HIV and bladder cancer. The objective was to assess the prevalence and characteristics of bladder cancers in HIV‐infected patients in our hospital.ResultsBased on our administrative HIV database (6353 patients), we found 15 patients (0.2%) with a bladder cancer. Patients’ characteristics are presented in Table 1. Patients were mostly men and heavy smokers. Their median nadir CD4 cell count was below 200 and most had a diagnosis of AIDS. A median time of 14 years was observed in those patients, between the diagnosis of HIV‐infection and the occurrence of bladder cancer, although in patients much younger (median age 56) than those developing bladder cancer without HIV infection (71.1 years) [4]. Haematuria was the most frequent diagnosis circumstance in HIV‐infected patients who had relatively preserved immune function on highly active antiretroviral therapy (HAART). Histopathology showed relatively advanced cancers at diagnosis with a high percentage of non transitional cell carcinoma (TCC) tumor and of TCC with squamous differentiation, suggesting a potential role for human papilloma virus (HPV) co‐infection. Death rate was high in this population.ConclusionsBladder cancers in HIV‐infected patients remain rare but occur in relatively young HIV‐infected patients with a low CD4 nadir, presenting with haematuria, most of them being smokers, and have aggressive pathological features that are associated with severe outcomes.
Prevalence of monoclonal gammopathy in HIV patients in 2014
Authors: Genet Philippe , Sutton Laurent , Chaoui Driss , Al Jijakli Ahmad , Gerbe Juliette , Masse Virginie , Wifaq Bouchra 
Published: November 2014

IntroductionIn non‐HIV patients, Monoclonal Gammopathy of Undetermined Significance (MGUS) is associated with an increased risk of subsequent development of haematologic malignancies, especially multiple myeloma (MM) and it has been recently demonstrated that MM is always preceded by a MGUS phase. A higher prevalence of MGUS and MM has been observed in HIV patients compared to the general population. Nevertheless, it has been shown that MGUS in the context of HIV can disappear with antiretroviral therapy (ART). So, measuring MGUS prevalence in HIV patients in the recent period appears of special interest.Materials and MethodsFrom January to June 2014, in each out‐patient seen in our unit, a serum protein electrophoresis was performed.ResultsA total of 393 patients were screened. Eight patients with HIV2 and one patient with HIV1+HIV2 infection were excluded. Finally, 383 patients (173 female, 210 male) with HIV1 infection were analyzed. Characteristics of patients were as follows: median age 42.2 years (19.1–79.1), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co‐infection 47 (18.8%), median CD4 610 (2–1758), CD8 793 (113–4010), presence of a past AIDS event for 88 patients (23%). Median time with HIV infection was 11 years (0–30). Three hundred fifty‐nine patients (93.7%) were on ART for a median duration of 105 months (0–287). For 320 patients (83.6%), viral load was below 50 viral copies/ml. Twelve cases of MGUS (3.1%) were observed: IgG Kappa (five cases), IgG Lambda (five cases), biclonal with two IgG Kappa (one case) and in one case, three monoclonal immunoglobulins were observed (IgG Kappa×2+IgG Lambda). The monoclonal immunoglobulin's level was low and below 1 g/l in all cases except two (2.1 and 11.6 g/l). No factor was found to be predictive of the presence of MGUS in particular age, CD4, HBV/HCV co‐infection, viral load or ART.ConclusionsIn the context of modern ART, the prevalence of MGUS remains above those observed in the general population. Even if the level of monoclonal spike observed in our cohort is generally low, an excess risk of subsequent development of MM could be present. Nevertheless, a prospective follow‐up of HIV patients with MGUS is necessary to determine this risk.
Prevalence of anal human papillomavirus infection and cytologic abnormalities among HIV‐infected and HIV‐uninfected men who have sex with men
Authors: Latini Alessandra , Gabriella Dona Maria , Ronchetti Livia , Giglio Amalia , Moretto Domenico , Colafigli Manuela , Laquintana Valentina , Frasca Mirko , Zaccarelli Mauro , Antinori Andrea , Cristaudo Antonio , Giuliani Massimo 
Published: November 2014

IntroductionHuman papillomavirus (HPV) is responsible for 85% of anal cancers. Recently, anal cancer incidence has been increasing, particularly in men who have sex with men (MSM). Cytology may be a useful tool for the detection of anal precancerous lesions. We assessed the prevalence and determinants of anal HPV infection and cytologic abnormalities among HIV‐infected and ‐uninfected MSM.Materials and MethodsMSM ≥18‐year‐old attending an STI clinic in Rome (Italy) were enrolled. Anal cytologic samples were collected in PreservCyt (Hologic) using a Dacron swab. The Linear Array HPV Genotyping Test (Roche Diagnostics) was used for the detection and genotyping of 37 mucosal HPV types. Liquid‐based cytological slides were obtained using a ThinPrep2000 processor (Hologic). The morphology of the anal pap‐test was classified following the Bethesda 2001 guidelines.ResultsWe enrolled 180 HIV‐infected (median age 41 years, IQR 33–47) and 438 HIV‐uninfected MSM (median age 32 years, IQR: 27–39). Most of the individuals were Caucasian (92.2% and 97.0%, respectively). HPV prevalence, both overall (93.3% vs 72.4%, p<.001) and by high‐risk (HR) HPV types (80.5% vs 56.0%, p<.001), was significantly higher among HIV‐infected than HIV‐uninfected individuals. HPV‐multiple infections were evidenced in 48.2% of the HIV‐uninfected and 76.1% of the HIV‐infected MSM (p<.001). HPV16 was the most prevalent genotype in both groups (23.3% in HIV‐positive and 17.6% in HIV‐negative MSM). HPV6 and 84 were the most frequent low‐risk types in both cohorts. Anal cytologic abnormalities were found in a significantly higher proportion of HIV‐infected MSM (46.1% vs 27.9%, p<.001). H‐SILs (high‐grade squamous intraepithelial lesions) were exclusively observed among the HIV‐infected individuals, although at a low prevalence (1.2%).ConclusionsA high prevalence of anal HPV infection and cytologic abnormalities was evidenced in both populations. Nonetheless, HIV‐infected MSM showed a significantly higher rate of HPV infection and abnormal cytology, confirming that HIV‐1 infection poses a significant risk for anal HPV infection as well as for anal cellular abnormalities. Screening for anal cancer, which is currently the most frequent non‐AIDS‐defining cancer in HIV‐positive MSM, should be considered for this population. Moreover, vaccination strategies for the prevention of HPV infection should be taken into account.
Pregnancy outcomes in women growing up with perinatally acquired HIV in the United Kingdom and Ireland
Authors: Byrne Laura , Thorne Claire , Foster Caroline , Tookey Pat 
Published: November 2014

IntroductionIn the United Kingdom and Ireland more than 40% of individuals living with perinatally acquired HIV are now aged >16. Globally, increasing numbers of women with perinatally acquired HIV are becoming pregnant, but data on fertility and pregnancy outcomes is scarce. We present pregnancy outcome data for this emerging cohort.MethodsPregnancies in diagnosed HIV‐infected women in the United Kingdom and Ireland, and children diagnosed with HIV, are reported to the National Study of HIV in Pregnancy and Childhood. We analyzed data on pregnancies in women diagnosed aged ≤13 with perinatally acquired HIV, reported by June 2014.ResultsA total of 759 females born before 2001, diagnosed with perinatally acquired HIV aged ≤13 years, and in care in the UK and Ireland have been reported. Forty‐four of these (6%) have had at least one pregnancy reported, with nineteen 2nd and four 3rd/4th pregnancies. Women's year of birth ranged from 1985 to 1996; 60% of women were UK/Irish‐born and 39% African‐born. Twenty one percent were diagnosed at <2 years, 39% at 2–7 and 41% at 8–13 years. Nine pregnancies were conceived in 2005–07, 22 in 2008–10 and 36 in 2011–13. Median age at conception of first pregnancy was 19 years. CD4 count was >500 cells/µL in 36% of first pregnancies, 350–499 in 15% and <350 in 49%. Women were on antiretroviral therapy (ART) at conception in 71% of pregnancies. There were 51 singleton live births, 2 miscarriages, 9 terminations and 5 continuing to term. In 17 live births to women not on ART at conception, median gestational age at start of ART was 17 weeks (range 3–29). HIV viral load was <50 copies/mL near delivery in 64% of live births, 51–1000 in 31% and >1000 in 5%. Forty four percent of live births were delivered by elective caesarean section (CS), 27% by emergency CS, 27% by planned vaginal delivery and with one unplanned vaginal delivery. Of 29 live births with viral load <50, 31% were delivered by elective CS, 17% by emergency CS and 52% by vaginal delivery. Fifteen percent of infants were delivered at 32–36 weeks gestation, and 2% at 30 weeks; 16% weighed 1.5–2.5 kg and 16% weighed <1.5 kg. Among 38 of the 51 infants where infection status is already reported, one is perinatally infected.ConclusionsCurrently at least 6% of perinatally infected women in care in the UK and Ireland have experienced one or more pregnancies. Linking paediatric, pregnancy and second generation data will enable further monitoring of pregnancy outcomes in this newly emerging population.