bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring renal function during combination therapy with telaprevir in HIV/HCV co‐infected patients with advanced/fibrosis cirrhosis
Authors: Puzzolante Cinzia , Vecchia Marco , Zona Stefano , Borghi Vanni , Guaraldi Giovanni , Mussini Cristina 
Published: November 2014

IntroductionTelaprevir (TVR) plus peg interferon (PEG‐IFN) and ribavirin (RBV) substantially increase treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection but data about its safety in HIV patients with cirrhosis are lacking. Our purpose was to evaluate estimated Glomerular Filtration Rates (eGFR) variations during combination therapy in a difficult‐to‐treat HIV/HCV population with advanced fibrosis/cirrhosis through three different scores commonly used in clinical practice: CKD‐EPI (Chronic Kidney Disease Epidemiology Collaboration), Modification of Diet in Renal Disease (MDRD) scores (that consider gender, ethnicity, age, serum creatinine level [SCL]) and MDRD 6 variable (that considers the previous parameters plus blood urea nitrogen and serum albumin). Second objective was to identify any association between creatinin clearance and haemoglobin (Hb) variation during combination therapy.Materials and MethodsWe conducted an observational retrospective study including 18 HIV/HCV patients attending our clinic who started combination therapy for HCV, including in the analysis the first 16 weeks of therapy. Treatment included TVR 1125 mg BID (twice a day) for 12 weeks, PEG‐IFN α‐2a 180 mcg QW and RBV daily dose according to body weight (800 mg in individuals <60 kg; 1000 mg in individuals 60–75 kg; 1200 mg in individuals >75 kg). Advanced fibrosis was defined as Metavir score=F3 or Ishak 3–4 and cirrhosis was defined as Metavir score F4 or Ishak 5–6 assessed by liver biopsy or transient elastography respectively. P per trend were assessed to evaluate any change of SCL and eGFR (according to different formulas). Multilevel linear regression analysis was performed to estimate factors associated with reduction of Hb.ResultsBaseline characteristics and HCV virological responses were collected. Figure 1 shows median SCL and eGFR trends across follow‐up period: SCR p‐per‐trend was 0.28, for CKD‐EPI was 0.50, for MDRD was 0.48, for MDRD‐6 variables was 0.27. Hb trend was also assessed and a significant decrease of Hb across follow‐up (p per trend <0.001) was noted. Multilevel regression analysis found an association between SCL and Hb change, after adjustment for age, sex, basal BMI, tenofovir exposure and proteinuria (assessed at baseline) as shown in Table 1.ConclusionsIn our experience, combination therapy with TPV in cirrhotic HIV‐HCV patients did not significantly affect renal function. As expected, Hb levels decreased during treatment and it is likely related to RBV exposure. In multivariable analysis, reduction of Hb appeared to be related to SCL higher levels, thus suggesting even a mild decrease of renal function.
Evaluation of the degree of liver fibrosis and genetical characteristics in HIV patients with spontaneous clearance of HCV in Cartagena, Spain
Authors: Jesús Vera Méndez Francisco , Jimeno Almazán Amaya , Smilg Nicolás Clara , Alcaraz Vidal Begoña , Martínez Madrid Onofre , Alcalde Encinas Mar , García García Josefina , Martínez Fernández Lorena , Conesa Zamora Pablo , Ruiz Belmonte Elena , Escribano Viñas Paloma , Trujillo Santos Javier 
Published: November 2014

IntroductionSingle‐nucleotide polymorphisms (SNPs) in the region of the Interleukin 28B (IL28B) gene on chromosome 19, coding for the interferon (IFN)‐λ3, are involved in hepatitis c virus (HCV), spontaneous clearance. There is little information on the degree of liver fibrosis (LF) in HIV patients, who have had spontaneous clearance of HCV. Our objective in this study is to assess the degree of liver fibrosis in this population, as well as to identify key genetic characteristics associated with spontaneous clearance.Materials and MethodsRetrospective descriptive study that evaluated from 1 January 2013 to 30 May 2014, the HIV‐HCV coinfected patients in which it has been demonstrated spontaneous clearance of HCV infection. The main variables analyzed were (1) genetics: Haplotype determination of genetic polymorphism SNP rs12979860 in the region of IL 28B gene and (2) grade of LF measured in kilopascals (kPa) by transient elastography (TE).ResultsWe evaluated 205 patients with HIV and HCV coinfection, of whom, 17 patients (8.3%), presented spontaneous clearance. Fourteen patients (82.4%) had HIV CV<20 copies/mL, while the mean CD4 cell count was 396 (SD: 245) cells/mcL. Nine (53%) patients were analyzed for SNP rs12979860 of IL 28B gene. Nine patients (100%) had the CC haplotypes, and no cases of CT and TT haplotypes were detected (p<0.001). LF was measured by TE in 12 (70.6%) patients. The median of LF (Kpa) was 5.95 (IQR 4.78). In four patients (33.3%) were observed significant LF (F3–F4). In the univariate analysis, no significant differences in the median of LF (Kpa) of HIV patients with spontaneous clearance of HCV were observed with respect to the coinfected HIV‐HCV patients with SVR to antiviral therapy (N=34; median 9.6 Kpa; IQR: 10.7; p=0.92) or the coinfected HIV‐HCV group who did not receive antiviral therapy (N=124; median 8.5 kPa; IQR: 7.65; p=0.85).ConclusionsSpontaneous clearance of HCV in our series of patients coinfected with HIV infection represents an uncommon clinical phenomenon. The immune status was preserved and most patients had HIV virological suppression. In all patients in which the IL 28B genetic polymorphism was determined, CC haplotypes were found. The degree of LF (Kpa) in this population was low (<9.5 Kpa) and a low proportion of subjects showed significant LF (F3–F4). No differences in the degree of LF were found in this group compared to coinfected patients receiving HCV treatment with SVR and compared to untreated patients coinfected with HIV‐HCV.
Risk of liver decompensation assessed in HIV/HCV co‐infected individuals with advanced liver fibrosis: a faster countdown experience
Authors: Pedro Alves Joao , Peres Susana , Borges Fernando , Cláudia Miranda Ana , Baptista Teresa , Ventura Fernando , Antunes Isabel , Nina Jaime , José Campos Maria , Aldir Isabel , Mansinho Kamal 
Published: November 2014

IntroductionCirrhosis secondary to HCV infection is expected to peak in the next decade, particularly in the HIV co‐infected subgroup and has become a leading cause of morbidity among these individuals. Efforts must be done to estimate the risk of liver decompensation (LD) in the short term, in order to define the appropriate time for HCV treatment.Materials and MethodsRetrospective observational cohort study aimed to assess the risk of LD among a group of HIV/HCV co‐infected patients diagnosed in the past 23 years in a central hospital of Lisbon. Inclusion criteria: (1) advanced liver fibrosis ≥F3; (2) HCV treatment naïve or without sustained virologic response (SVR). Patients had a one to five years period of follow‐up. Multiple linear regression, Mann‐Whitney and Kendall were the statistical tests performed.ResultsFrom 444 HIV/HCV co‐infections, 66 met the inclusion criteria, with preponderance of male gender (82%), 35–45 years of age (55%), genotype 1a (52%), a mean of 13 years of co‐infection and an AIDS stage documented in 65%, though the majority is under antiretroviral therapy (86%) and have TCD4+>500 µ/L (59%). Half (52%) showed evidence of steatosis, many of these (41%) presenting a history of alcoholism or overweight (BMI ≥25 Kg/m2). Pre‐cirrhotic (F3 or F3/4) or cirrhotic (F4) stage was documented in 36 and 30 patients respectively. After staging, 28 (42%) initiated HCV treatment and SVR was achieved in 8 (29%) of those. Five (14%) pre‐cirrhotic and twelve (40%) cirrhotic patients experienced at least one LD episode: 8 vs 28 cumulative events at five years and 2.8 vs 1.8 average years up to the first LD episode for pre‐cirrhotic vs cirrhotic. The probability of remaining free of LD for pre‐cirrhotic vs cirrhotic patients was 97% vs 78% (p≤0.01) at one year; 88% vs 65% (p≤0.001) at three years and 71% vs 44% (p≤0.001) at five years. Positive correlation was found between LD and the cirrhotic stage (vs pre‐cirrhosis, p≤0.001), baseline AST ≥100 µ/L (vs <100 µ/L, p≤0.01) and platelet count <120 x 109/L (vs >120 x 109/L, p≤0.05).ConclusionsCirrhosis accounts for a significant superior risk of LD. The time up to the first LD event differed in only one year between pre‐cirrhotic and cirrhotic, standing for the importance of a rapid treatment referral in both subgroups. Modifiable risk factors that accelerate fibrosis are prevalent in HIV/HCV co‐infected patients. Low platelet count, elevated AST and F4 stage predict the rapid progression to LD and the need for early HCV treatment. Large studies are required for further support of these results.
Increased incidence of sexually transmitted diseases in the recent years: data from the ICONA cohort
Authors: Cingolani Antonella , Zona Stefano , Girardi Enrico , Cozzi Lepri Alessandro , Monno Laura , Quiros Roldan Eugenia , Guaraldi Giovanni , Antinori Andrea , d'Arminio Monforte Antonella , Marcotullio Simone ,   on behalf of ICONA Foundation Study
Published: November 2014

IntroductionSexually transmitted diseases (STDs) data collected in HIV+ patients could be used as indicator of risky sexual behaviour possibly linked to HIV transmission. We described the STDs incidence over time and identified higher incidence factors.MethodologyAll patients in the ICONA Foundation Study enrolled after 1998 were included. STDs considered: any‐stage syphilis, human papilloma virus (HPV) diseases, gonococcal and non‐gonococcal urethritis, herpes simplex virus (HSV) genital ulcers, vaginitis and acute hepatitis B virus (HBV), hepatitis A virus (HAV), and hepatitis C virus (HCV) infections (only for non‐IVDU (intravenous drug user) patients). STDs incidence rate (IR): number of STDs divided by person years of follow‐up (PYFU). Calendar periods: 1998–2002, 2003–2007 and 2008–2012. Predictors of STDs occurrence were identified using Poisson regression and sandwich estimates for the standard errors were used for multiple STD events.ResultsData of 9,168 patients were analyzed (median age 37.3 (SD=9.3), 74% male, 30% MSM). Over 46,736 PYFU, 996 episodes of STDs were observed (crude IR 17.3/1,000 PYFU). Median (IQR) CD4/mmc and HIV‐RNA/mL at STD: 433 (251–600) and 10,900 (200–63,000). Highest crude IRs were observed for any‐stage syphilis (3.95, 95% CI 3.59–4.35), HPV diseases (1.96, 1.71–2.24) and acute hepatitis (1.72, 1.49–1.99). At multivariable analysis (variables of adjustment shown in Figure 1), age (IRR 0.82 per 10 years younger, 95% CI 0.77–0.89), MSM contacts (IRR 3.03, 95% CI 2.52–3.64 vs heterosexual) and calendar period (IRR 1.67, 95% CI 1.42–1.96, comparing 2008–2012 with 1998–2002) significantly increased the risk of acquiring STDs. Moreover, having a HIV‐RNA >50 c/mL (IRR 1.44, 95% CI 1.19–1.74 vs HIV‐RNA <50 c/mL) and current CD4+ cell count <100/mmc (IRR 4.66, 95% CI 3.69–5.89, p<0.001 vs CD4+ cell count >500) showed an increased risk of STDs. Being on ARV treatment significantly reduced the risk of developing an STD (IRR 0.37, 95% CI 0.32–0.43) compared to ART‐naïve people, even in the situation of temporary interruption of treatment (IRR 0.51, 95% CI 0.39–0.43) (see Figure 1).ConclusionsThe overall incidence of STDs has been increasing in the recent years. Interventions to prevent STDs and potential further spread of HIV infection should target the recently HIV diagnosed, the young population and MSM. Being on ARV treatment (potentially an indicator of whether a person is regularly seen for care) seems to reduce the risk of acquiring STDs independently of its viro‐immunological effect.
Predictors of lack of serological response to syphilis treatment in HIV‐infected subjects
Authors: Spagnuolo Vincenzo , Poli Andrea , Galli Laura , Cernuschi Massimo , Nozza Silvia , Maillard Myriam , Gianotti Nicola , Hasson Hamid , Bossolasco Simona , Lazzarin Adriano , Castagna Antonella 
Published: November 2014

IntroductionThe aim of this study was to determine factors associated with lack of serological response (LSR) to treatment of syphilis among HIV‐infected subjects.Materials and MethodsRetrospective, longitudinal study on HIV‐infected subjects diagnosed and treated for syphilis and with an assessable serological response between 1 January 2004 and 15 September 2013. LSR was defined as a <4‐fold decline of rapid plasma reagin (RPR) titer or a failed reversion to nonreactive (if RPR ≤1:4 at diagnosis) after one year since treatment. Diagnoses of syphilis were staged in early syphilis (primary, secondary and early latent) or late syphilis (tertiary and late latent) according to clinical examination and patient's history. Syphilis was classified in new infections [NI: positive RPR and TPHA (Treponema pallidum Haemagglutination assay) titers in subjects without previous history of syphilis] or re‐infections [ReI: a ≥4‐fold increase of RPR titer in subjects previously successfully treated for syphilis]. Syphilis treatment was prescribed according to CDC guidelines. The crude incidence rates (IRs) of LSR were calculated per 1000‐person months of follow‐up (PMFU) as the total number of LSR episodes divided by the cumulative time contributed by all subjects (interval time since each syphilis diagnosis and the date of ascertainment of response). Results are described as median (IQR) or frequency (%).Results565 diagnoses of syphilis with an assessable serological response in 421 patients; 458 (81%) were early syphilis, 189 (33%) were NI, 376 (67%) were ReI. At first, diagnosis of syphilis median age was 41 (36–47) years, 419 (99.5%) males, 391 (93%) MSM, HIV‐infected since 7.7 (3.5–12.9) years, 75 (18%) HCV or HBV co‐infected, 56 (13%) with a previous AIDS diagnosis, 82 (19%) antiretroviral treatment naïve, 102 (24%) with HIV‐RNA ≥50 cp/mL, CD4+=576 (437–749) cells/mm3, nadir CD4+=308 (194–406) cells/mm3. LSRs were observed in 70/565 (12.4%) treated syphilis. Incidence of LSR decreased over time [2004–2008 IR=25.1 (17.2–33.1)/1000 PMFU; 2009–2010 IR=21.1 (12.3–29.9)/1000 PMFU; 2011–2013 IR=10.6 (5.1–18.2)/1000 PMFU; Poisson regression: p=0.001]. Results of univariate and multivariate analysis on the risk of LSR are reported in Table 1.ConclusionsIn HIV‐infected subjects we observed 12% of LSR to treatment of syphilis. LSR was associated with an older age, late syphilis, lower nadir CD4+ and detectable HIV viral load.
Ongoing epidemic of lymphogranuloma venereum in HIV‐positive men who have sex with men: how symptoms should guide treatment
Authors: Mohrmann Gerrit , Noah Christian , Sabranski Michael , Sahly Hany , Stellbrink Hans‐Jürgen 
Published: November 2014

IntroductionLymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by chlamydia trachomatis (CT) genotype L (L1, L2 and L3). Recent outbreaks of LGV in Europe and North America affected mainly men who have sex with men (MSM). Infections with CT serotypes D‐K are mostly associated with mild symptoms or may be clinically silent. However, infections with L genotypes are more invasive and induce anogenital ulcer or inguinal lymphadenopathy.Materials and MethodsBetween 2003 and 2013, anal or genital CT infections were diagnosed in 471 symptomatic patients attending the Infectious Diseases Center Hamburg (ICH). CT DNA was detected by PCR. CT genotyping of positive samples was performed by sequence analyses of omp1 PCR products (samples between 2003 and 2010). Samples between 2012 and 2013 were analyzed by genotype L specific real‐time PCR.ResultsIn total, 221 LGV patients were identified (3 in 2003; 11 in 2004; 26 in 2005; 33 in 2006; 24 in 2007; 16 in 2008; 18 in 2009; 15 in 2010; 17 in 2011; 26 in 2012 and 32 in 2013). One hundred ninety‐eight of 221 (89.6%) patients with LGV were HIV‐infected; 10 of 221 (4.5%) were HIV‐negative, and the HIV‐status unknown in 13 (5.9%). The majority of LGV positive patients (204/221; 92%) had anorectal symptoms (bloody proctitis, rectal pain, purulent or mucous discharge, tenesmus, constipation), compared to 17/221 (8%) who presented with genital symptoms as urethritis, genital ulcer or inguinal lymphadenopathy. Of 283 CT‐positive patients with anorectal symptoms, genotype L was detected in 205 (72%), while non‐L genotypes (D‐K) were found in 78 (28%). In contrast, genotype L was found in only 6% of patients with genital symptoms (11/177), whereas 94% (166/177) were infected with non‐L genotypes only.ConclusionsThe epidemic of LGV among predominantly HIV+ MSM is ongoing. LGV might be underdiagnosed, especially in patients with anorectal symptoms. Infections with CT serotypes D‐K are more often associated with urogenital symptoms or asymptomatic infection, whereas LGV genotypes are found most frequently in patients with rectal/intestinal symptoms. Anorectal CT infections in MSM should be further characterized by genotyping for LGV, as for LGV three weeks of doxycycline treatment are recommended. CT genotypes D‐K generally require shorter antibiotic treatment. If CT genotyping is not available, the duration of treatment should be prolonged to three weeks empirically for CT‐positive patients with anorectal or intestinal symptoms.
Should screening for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV‐men who have sex with men be recommended?
Authors: Pérez‐Hernández Isabel , Palacios Rosario , González‐Doménech Carmen , García Victoria , Márquez Manuel , Clavijo Encarnación , Santos Jesús 
Published: November 2014

IntroductionSexually transmitted infections (STI) like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of HIV acquisition [1]. It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men (MSM) [2]. The aim of this study was to know the prevalence of CT and/or NG infections in asymptomatic HIV‐MSM and the related factors.Materials and MethodsProspective study of a cohort of asymptomatic HIV‐MSM with follow‐up in Malaga (southern Spain) during October 2012–May 2014. Patients with an opportunistic event or who received active antibiotic therapy for CT and/or NG in the previous month were excluded. All of them completed a questionnaire about sexual behaviour, barrier methods and recreational drugs use. Demographical, epidemiological, clinical, analytical and therapeutic data were also collected. Pharyngeal and rectal swabs, and urine samples were collected to be tested for CT and NG by nucleic acid amplification test (c4800 CT/NG. Roche Diagnostics, Mannheim, Germany) [3]. Statistics analysis: SPSS 17.0.Results255 patients were asked to participate and 248 of them accepted. Median age was 37.7 (30.6–46.3) years, median time since HIV diagnosis was 47.7 (10.5–104.1) months, and median CD4 cells count was 607 (440–824) cell/µL. There were 195 (78.6%) patients on antiretroviral therapy; 81.5% of them had undetectable viral load. 80.5% of the patients had a past history of STI. Infection by CT and/or NG was diagnosed in 24 (9.7%) patients. Overall four urine samples, two pharyngeal, and 15 rectal ones were positive for CT, and five pharyngeal and five rectal swabs were positive for NG. Two patients were co‐infected by CT and NG: one with CT in urine and both in rectum, another with CT in urine and rectum and NG in pharynx. One patient presented CT in pharynx and rectum, and two patients NG in pharynx and rectum. Positive CT and/or NG tests were only related with detectable HIV viral load (OR 3.08, 95% CI 1.2–7.4; p=0.01). It was not related with sexual behaviour, nor with alcohol or recreational drugs use.ConclusionsSTI screening had a great acceptance in this population. There was a high prevalence of asymptomatic CT and/or NG infections. Rectum sample was the most effective one. Viral suppression could protect from these STI. Screening should be recommended in HIV‐MSM.
Service impact of a change in HIV‐1 viral load quantification assay
Authors: Tipple Craig , Oomeer Soonita , Dosekun Olamide , Mackie Nicola 
Published: November 2014

IntroductionDue to discontinuation of the Siemens Versant HIV‐1 RNA (bDNA) assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV‐1 viral load (VL) assay (Roche) in April 2013. This assay has a lower cut‐off of 20 RNA copies/mL (compared with <50 for the Siemens assay). Our laboratory demonstrated previously that a significant proportion (18%) of patients undetectable using bDNA HIV‐1 RNA quantification exhibited low level viraemia (LLV) using the new assay. Local guidelines recommend that patients stable on therapy receive twice‐yearly VLs. We evaluated the impact of the introduction of the new assay on our clinical service.MethodsA retrospective cohort analysis of treated patients with stable undetectable VL by bDNA (<50 copies/mL) followed by ≥ one low‐level (<400 copies/mL) VL with the Roche assay. Demographic data were collected in addition to frequency of VL testing and genotypic resistance assays. Referrals to virtual clinic (VC) were recorded. Patients were identified using laboratory data and information collected from electronic patient records. Results were analyzed with SPSS v18.ResultsOne hundred and ninety patients were included. Demographics: 79.5% male; 60.6% homosexual; mean age of 46 years. Duration on stable treatment was 46.35 (std. dev. 38.15) months. Current treatment regimens were 43.3% PI‐based; 43.3% NNRTI‐based and 13.7% other. Patients were stratified into VL 20–49 copies/mL (n=109); VL 50–199 copies/mL (n=71) and VL 200–399 copies/mL (n=10). In total, there were 471 VLs measured of which 274 were additional as a result of the assay switch. This resulted in six HIV‐1 genotype requests and 16 VC discussions (Table 1). Longer duration on HAART was associated with reduced frequency of VL testing. The relative risk of ongoing detectability according to drug class are: PI 1.62 (95% CI 1.18–2.21); NNRTI 0.507 (95% CI 0.30–0.85) and other 1.09 (95% CI 0.48–2.43).ConclusionsChanges in assay can result in difficulties in interpretation of patient results. The assay switch in our service had significant impact on patient and staff time and cost with an increase in patient recalls; increased frequency of VL measurement, genotypes and discussions in VC. Choice of assay is paramount to running an efficient and cost‐effective clinical service.