Suchergebnisse

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.

BackgroundCD4/CD8<0.8 is a surrogate marker of immune‐activation/immunosenescence and independently predicts mortality in the HIV‐infected patients due to non‐AIDS related events. Most studies showed that patients on antiretroviral therapy (ART) often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. Primary objective of the study was to explore the impact of CD4/CD8<0.8 as independent predictor of HIV‐associated non‐AIDS (HANA) conditions and multimorbidity (MM) in HIV patients. In patients with no previous history of cardiovascular disease (CVD) a particular insight is provided in the association between impact of CD4/CD8<0.8 and risk prediction of CVD or radiological markers of subclinical CVD.Materials and Methods914 consecutive patients attending Modena Metabolic HIV Clinic were evaluated in a cross‐sectional retrospective study. Inclusion criteria: stable ART from ≥2 years; HIV‐RNA plasma levels<40 copies/mL; stable CD4 count≥350/mmc. CD4/CD8 strata (0.8) was chosen as a cut off representing the median value of the cohort. MM was defined as the presence of≥2 HANA conditions including standard defined: chronic kidney disease, hypertension, previous CVD events, osteoporosis and diabetes mellitus. Calendar year of ART initiation was defined: "PreART" (<2000); "EarlyART" (2000–2005) and "LateART" (>=2006). High CVD risk was defined for Framingham Risk Score (FRS)≥6. Subclinical CVD was defined using cardiac CT scan for calcium score (CAC)≥100. Logistic univariate and multivariable adjusted analysis were performed to assess relationships between variables.ResultsDemographic and HIV‐specific variables distribution in patients with and without MM are shown in Table 1.Figure 1 shows HANA distribution across CD4/CD8 strata: CVD prevalence only appeared to be higher in patients with no CD4/CD8>0.8.In multivariable analyses CD4/CD8<0.8 was not an independent predictor of MM (OR=1.225, CI 0.891; 1.681, p=0.211) after adjustment for age, gender and BMI. Patients with CD4/CD8<0.8 displayed higher CVD risk but not higher prevalence of subclinical CVD. At multivariable analyses CD4/CD8<0.8 remained predictor of higher CVD risk (OR=0.65, CI 0.47–0.917, p=0.014) after correction for sex, BMI, age strata and HIV infection duration.ConclusionsLow CD4/CD8 ratio was not associated with MM prevalence. Patients with CD4/CD8<0.8 ratio displayed higher prevalence of CVD. At multivariable logistic regression CD4/CD8<0.8 is an independent prepredictor of enhanced CVD risk. This may support role of immune‐activation/senescence in the pathogenesis of CVD.

IntroductionThe aim was to determine the prevalence of lung and heart abnormalities on thoracic CT scans in HIV‐infected patients who were treated with antiretroviral therapy (ART).Material and MethodsThoracic CT scans of 903 patients infected with HIV (mean age 48±7 yrs, 29% females) were reviewed by three radiologists by consensus. Patients were phenotyped according to smoking status, pack years and years since cessation for ex‐smokers. Individuals known to have active lung or heart disease at the time of CT scanning were excluded. Multimorbidity lung and heart disease (MLHD) was defined by the presence of >2 lung or heart abnormalities on the CT scan.ResultsPrevalence of lung abnormalities were: 326 patients (36.1%) with emphysema, 271 (30.0%) with bronchiolitis, 44 (4.9%) with non‐calcified lung nodules, 568 (63%) with significant bronchial wall thickening, 150 (16.7%) with bronchiectasis, 9 (1%) with interstitial lung disease. Overall, 445 patients (49.3%) had >2 lung abnormalities. Imaging findings suggestive of prior myocardial infarction (MI) were found in 1.4% (13 patients); 26.6% (240 patients) had CAC scores of 1 to 100, and 9.8% (89 patients) had CAC>100. 13.6% (123 patients) of the patients had CAC>100 and/or previous MI. MLHD was present in 484 patients (53.6%) and among 78 patients (16%) who never smoked. Table 1 describes CT findings according to pack year and stop smoking groups vs never smokers.MLHD increased proportional to cumulative smoking history (p for trend <0.001) and decreased in proportion to the number of years since smoking cessation (p for trend=0.017). Independent predictors for MLHD were: age (OR=1.07, CI 1.05–1.10), sex (OR=1.59, CI 1.15–2.19), current smoking (OR=1.76, CI 1.08–2.89), and pack‐years history of smoking (OR=1.03, CI 1.02–1.05). In patients who never smoked, nadir CD4<200 was significantly associated with MLHD after adjustment for age and sex (OR=1.98, CI 1.98–3.63).ConclusionsMLHD is common in HIV‐infected individuals even in non‐smokers. Reduced CD4 count (hence severity of HIV infection) may be an important risk factor for chronic lung and heart disease. Thoracic CT scans may provide an excellent screening tool to detect MLHD in HIV‐infected patients.

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.

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.