Incidence of recently acquired hepatitis C virus infection among HIV-infected patients in southern Spain.

OBJECTIVES: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. METHODS: Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. RESULTS: All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. CONCLUSIONS: The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.

Fat mass and obesity-associated gene variations are related to fatty liver disease in HIV-infected patients.

OBJECTIVES: Fatty liver disease (FLD) is frequently observed in HIV-infected patients. Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with FLD. Because genetic variants within the fat mass and obesity-associated (FTO) gene have been associated with both pathologies, our aim was to evaluate the association of single nucleotide polymorphisms (SNPs) within the FTO, previously related to obesity or T2DM, with FLD in HIV-infected patients. METHODS: FLD was defined as a value of the controlled attenuation parameter (CAP) ≥ 238 dB/m, obtained by transient elastography. Four SNPs within FTO intron 1 (rs11642841, rs8050136, rs9939609 and rs9940128) were genotyped in 421 individuals using a custom Golden Gate protocol. The results were replicated in a validation sample consisting of a further 206 HIV-infected patients. Multivariate logistic regression analyses were conducted in the entire population. RESULTS: Three SNPs (rs8050136, rs9939609 and rs9940128) were associated with FLD, with rs9940128 showing the strongest association. This polymorphism also showed an association with FLD in the validation sample. In total, rs9940128 was genotyped in 627 HIV-infected patients, including 267 (42.6%) FLD-diagnosed individuals. The frequency of FLD among rs9940128 AA carriers was 55.7% (63 of 113 individuals) and that in patients without this genotype was 39.7% (204 of 514 individuals) [P = 0.009; adjusted odds ratio 1.88; 95% confidence interval (CI) 1.17-3.01]. CONCLUSIONS: Variations within FTO may be predictors of FLD in HIV-infected patients independently of metabolic factors.

Core amino acid variation at position 110 is associated with sustained virological response in Caucasian patients with chronic hepatitis C virus 1b infection.

The aim of this study was to analyze the impact of core variations on sustained virological response (SVR) to pegylated interferon plus ribavirin (PEG-IFN/RBV) and its association with predictive factors of response in Caucasian patients infected with genotype 1 hepatitis C virus (HCV-1). Full-length core sequences were analyzed in 100 Caucasian HCV-1-infected patients who received therapy with PEG-IFN/RBV. The associations between variations in the core protein and SVR, as well as with predictors of SVR, were analyzed. Variations at core 62, 70 and 110 were selected as candidates. There were almost no variations at these positions among patients harboring HCV-1a. However, they were identified in 10 (30.3 %), 21 (63.6 %) and 13 (39.4 %) subjects with HCV-1b, respectively. Among the HCV-1b patients, 39.1 % individuals carrying core R62 and 70 % subjects with core R62G showed SVR (p = 0.141), and 66.7 % of HCV-1b patients harboring core R70 and 38.1 % with core R70Q achieved SVR (p = 0.157), whereas the rate of SVR was 70 % for individuals with core T110 and 15.4 % for those with core T110N (p = 0.004). No statistical interaction between core variations and IL28B genotype was observed. Patients with R70 showed higher median (interquartile range) baseline plasma levels of low-density-lipoprotein cholesterol (LDL-C) than those with R70Q (96 [86-118] mg/dL vs. 76 [54-88] mg/dL, p = 0.014). We concluded that a substitution at core 110 is associated with a lower rate of SVR in Caucasian HCV-1b-infected patients receiving PEG-IFN/RBV. Furthermore, the variation at the core 70 position is related to plasma levels of LDL-C in these patients.

Lack of short-term increase in serum mediators of fibrogenesis and in non-invasive markers of liver fibrosis in HIV/hepatitis C virus-coinfected patients starting maraviroc-based antiretroviral therapy.

The aim of this study was to analyze serum changes in mediators of fibrogenesis and in non-invasive markers of liver fibrosis among HIV/HCV-coinfected patients starting maraviroc (MVC)-based antiretroviral therapy. Patients included in this prospective pilot study met the following criteria: (1) HIV-infection, (2) detectable serum HCV-RNA, and ((3) started MVC. Transforming growth factor-ß1 (TGF-beta1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured in serum samples at baseline and 6 months after starting MVC. AST-to-platelet ratio index (APRI) was assessed at the same time points. Twenty-four patients were analyzed. Median (IQR) serum levels at baseline and after 6 months on MVC of TGF-beta1 were 27,295 (20,562-36,844) and 33,753 (18,973-46,130) pg/mL (p=0.116), of MMP-2 were 216 (186-274) and 241 (194-306) ng/mL (p=0.247), and of TIMP-1 were 237 (170-284) and 216 (171-271) ng/mL (p=0.415). APRI levels were 0.99 (0.53-3.46) at baseline and 0.83 (0.48-2.34) at 6 months (p=0.16). Serum mediators of liver fibrogenesis and fibrosis do not change significantly in HIV/HCV-coinfected patients in the short-term after starting MVC. As TGF-beta1 levels have been shown to increase over time in HCV infection and liver fibrosis worsens rapidly in HIV/HCV coinfection, these parameters seem to evolve in a different way in MVC-treated patients.

Insulin resistance is associated with liver stiffness in HIV/HCV co-infected patients.

BACKGROUND: The factors that influence liver fibrosis progression in patients co-infected with human immunodeficiency virus/hepatitis C virus (HIV/HCV) are not completely understood. It is not known if insulin resistance (IR), a condition that promotes liver fibrosis in HCV mono-infected individuals, is one of these factors. OBJECTIVE: To evaluate the association between IR and liver stiffness (LS). DESIGN: Multicentre cross-sectional study. PATIENTS: 330 patients co-infected with HIV/HCV. METHODS: LS was assessed by transient elastography, which has shown a high accuracy to predict significant fibrosis in patients co-infected with HIV/HCV. The outcome variable of the study was LS. Patients with LS> or =9 kPa were considered as having significant fibrosis. IR was calculated using the HOMA method. RESULTS: LS was > or =9 kPa in 150 (45%) patients. HOMA correlated with LS (Spearman's rho correlation coefficient, 0.37; p<0.0001). The median (Q1-Q3) HOMA in patients with LS> or =9 kPa was 3.30 (2.17-5.16) while it was 2.09 (1.37-3.22) in patients with LS <9 kPa (p<0.0001). Ninety-six (39%) individuals with a HOMA <4 and 54 (63%) with a HOMA > or =4 showed LS> or =9 kPa (p<0.0001). Analyses after excluding patients with cirrhosis yielded similar results. After multivariate analyses, age > or =40 years (adjusted odds ratio (AOR), 1.85; 95% confidence interval (CI), 1.03 to 3.29; p = 0.03), CD4 cell count <200 cells/ml (AOR, 3.45; 95% CI, 1.67 to 7.11; p = 0.001), hepatitis B virus co-infection (AOR, 9.25; 95% CI, 2.42 to 35.31; p = 0.001), and HOMA > or =4 (AOR, 5.33; 95% CI, 2.70 to 10.49; p<0.0001) were the independent predictors of LS> or =9 kPa. CONCLUSION: IR is associated with LS in patients co-infected with HIV/HCV.

Similar prevalence of hepatic steatosis among patients with chronic hepatitis C with and without HIV coinfection.

Hepatic steatosis (HS) is frequently observed in HIV-infected patients. It is not known whether HIV infection is an independent risk factor for HS development. We aimed to analyze whether HIV coinfection was associated with a higher frequency of HS in patients with chronic hepatitis C. This was a retrospective cross-sectional study. 574 subjects with chronic hepatitis C virus (HCV) infection were included, 246 (43%) of them coinfected with HIV. All of them underwent transient elastography with controlled attenuation parameter (CAP) measurement. HS was defined as CAP ≥ 248 dB/m. 147 individuals (45%) showed HS in the HCV-monoinfected group and 100 (40.7%) in the HIV/HCV-coinfected group (p = 0.318). HS was associated with body mass index (BMI) [<25 Kg/m2 vs. ≥25 Kg/m2, 67 (23.5%) vs. 171 (62.9%); p = 0.001], with plasma HDL-cholesterol [<50 mg/dL vs. ≥50 mg/dL, 122 (48.6%) vs. 95 (37.5%), p = 0.012], with plasma triglycerides [<150 mg/dL vs. ≥150 mg/dL, 168 (40.2%) vs. 65 (52.4%); p = 0.016] and with plasma total cholesterol [<200 mg/dL vs. ≥200 mg/dL, 181 (41%) vs. 53 (52.5%); p = 0.035]. In the multivariate analysis, HS was associated with BMI [adjusted OR (AOR) = 1.264 (1.194-1.339); p = 0.001], age [AOR = 1.029 (1.001-1.058); p = 0.047] and HCV genotype 3 infection [AOR = 1.901 (1.081-2.594); p = 0.026]. HIV coinfection was not associated with HS [AOR = 1.166 (0.719-1.892); p = 0.534]. In conclusion, HIV coinfection is not related with an increased frequency of HS in HCV-infected patients.

[Modification of empirical antimicrobial regimen during the first 72 hours of hospitalisation]. / Modificación del tratamiento antibiótico empírico en las primeras 72 horas de hospitalización.

OBJECTIVE: The aims of this study were to determine the empirical antibiotic therapy used in patients admitted to the Emergency Department who were later hospitalised, and to describe the antibiotic changes during their first days of hospitalisation. METHOD: All 14-year-old patients admitted to the Emergency Department who were started on antibiotic therapy and subsequently were hospitalised for at least 72 hours in an in-patient hospital ward, were included in a prospective observational study. Patients underwent daily follow-up during the first three days of hospitalisation. The type of infection, microbiological data and empirical antibiotic therapy and its changes were registered. RESULTS: 225 patients were included in this study. The most frequent types of infection diagnosed were infection of the respiratory airways, pneumonia and skin and soft-tissue infection. Amoxicillin-clavulanic acid was the most widely prescribed antibiotic followed by levofloxacin and third generation cephalosporins. Microbiological samples were taken in 80 (36%) patients. Of the 225 antimicrobial regimens started in the Emergency Department, 94 (42%) were changed during the first 72 hours of hospitalisation: 37 (16%) were completely modified, 31 (14%) were discontinued and antibiotics were added or stopped from the existing regimen in 26 cases (12%). Among these 94 patients whose treatment was changed, only in 40 (42%) there was a microbiological result for aiding in the adjustment of the antibiotic therapy. CONCLUSION: The frequency of early changes during inpatient hospitalisation to antimicrobial regimens which were initially prescribed in the Emergency Department is high. Microbiological results were rarely used to guide these changes.

Relationship between osteopenia, free testosterone, and vitamin D metabolite levels in HIV-infected patients with and without highly active antiretroviral therapy.

The prevalence of osteopenia in HIV-infected patients is high. However, the mechanisms implicated in bone mass loss in HIV infection are unclear. Because of this, we analyzed serum free testosterone and vitamin D3 hydroxylated metabolites in HIV-infected patients, with and without antiretroviral treatment, and the relation between them and osteopenia. Seventy-four HIV-infected patients were selected because they had frozen sera available at a date close to a DEXA evaluation. Free testosterone, 25(OH)D3, and 1,25(OH)2D3 were determined in frozen serum. There were no differences in free testosterone, 25(OH)D3, and 1,25(OH)2D3 levels between patients with and without osteopenia. 25(OH)D3 levels in naive and HAART-treated patients were 26.2 (10.3-32.8) and 33.1 (20.6-46.8) ng/ml, respectively (p = 0.04). 1,25(OH)2D3 levels in naive and HAART treated patients were 60.3 (49.2-80.8) and 85.5 (68-111.6) pmol/liter (p = 0.01). Free testosterone levels in 9 naive men and in 50 HAART-treated men were 42.6 (24.1-67.3) and 69.2 (47.5-112.1) pmol/liter, respectively (p = 0.04). In conclusion, HIV-infected patients with and without osteopenia showed similar levels of vitamin D metabolites and free testosterone. However, antiretroviral drug-naive patients showed lower serum levels of vitamin D metabolites and free testosterone than HAART-treated patients.

Relationship between low bone mineral density and highly active antiretroviral therapy including protease inhibitors in HIV-infected patients.

PURPOSE: The objectives of this study were to determine the prevalence of osteopenia and the factors associated with its presence in HIV-infected patients under highly active antiretroviral therapy (HAART) and to assess the changes of bone mineral density (BMD) in a population followed prospectively. METHOD: BMD was assessed by dual-energy X-ray absorptiometry (DEXA) scans at the lumbar spine and at the femoral neck in 78 HIV-infected patients who had previously received HAART as the first antiretroviral regimen and in 11 antiretroviral-naive HIV-infected patients. BMD measurements were repeated in 70 treated patients who had completed 1 year of follow-up. RESULTS: Thirty-seven (42%) patients showed osteopenia at any localization. The prevalence of osteopenia in PI-naive patients was 23% versus 49% in individuals who had received PI at any moment [p =.001; adjusted odds ratio (95% CI) = 0.11 (0.02-0.48)]. The frequency of osteopenia was significantly higher among men than among women [50% vs. 17%; p =.016; adjusted OR (95% CI) = 12.1 (2.22-66.20)]. The level of plasma albumin was independently associated with osteopenia [adjusted OR (95% CI) per each g/dL of plasma albumin decrease 2.55 (1.18-10)]. In patients in whom a second DEXA was done, no significant changes in BMD were found. CONCLUSION: The prevalence of osteopenia in HIV-infected patients on HAART is high. Loss of BMD is associated with PI therapy, low plasma albumin level, and male sex. Osteopenia does not progress after 1 year of continued HAART.

Interleukin 6 in cerebrospinal fluid of patients with meningitis is not a useful diagnostic marker in the differential diagnosis of meningitis.

We assayed interleukin 6 (IL-6) concentrations in cerebrospinal fluid (CSF) from patients affected by meningitis of different aetiologies, and verified whether IL-6 can be used as a diagnostic marker in the differential diagnosis of meningitis. We used a monoclonal antibody enzyme immunoassay to test 98 CSF samples classified as pyogenic (15), viral (15), self-resolving aseptic meningitis (20), other infectious meningitis (9), neoplastic (4) and normal CSF from patients with (20) and without (15) non-infectious neurological diseases. CSF IL-6 concentrations were increased in pyogenic meningitis (100%) and in more than 50% of viral and other subarachnoid space infections, and rarely in patients without central nervous system infections. Though patients affected by pyogenic meningitis showed the highest levels of CSF IL-6, only a cut-off point > or = 10000 pg/mL was able to discriminate pyogenic meningitis from those of other aetiologies with a specificity > or = 94% and a positive predictive value of > or = 0.75 but the sensitivity was < or = 60%. Therefore, CSF IL-6 concentration is not a good diagnostic marker in the differential diagnosis of meningitis.

[Incidence of phlebitis due to peripherally inserted venous catheters: impact of a catheter management protocol]. / Incidencia de flebitis secundaria por catéter venoso de acceso periférico e impacto de un protocolo de manejo.

OBJECTIVE: To assess the impact on the incidence of PPIVC by implementing a catheter management protocol and to determine risk factors for PPIVC development in hospitalized patients. METHOD: A total of 3978 episodes of venous catheterization were prospectively included from September 2002 to December 2007. A catheter management protocol was implemented during this period of time. The incidence and variables associated to the occurrence of PPIVC were determined. RESULTS: The incidence of PPIVC from 2002 to 2007 was 4.8%, 4.3%, 3.6%, 2.5%, 1.3% and 1.8% (p<0.001). Perfusion of amiodarone [adjusted OR (AOR) 25.97; 95% CI=7.29-92.55, p=0.0001] and cefotaxime (AOR 2.90; 95% CI=1.29-6.52, p=0.01) and the shift when the catheters were placed (AOR for morning vs. night shift 0.60; 95% CI=0.35-1.02, p=0.063) were independently associated to the development of PPIVC. A history of phlebitis was the only factor independently associated to phlebitis due to peripherally inserted central venous catheters (AOR 3.24; CI at 95% CI= 1.05-9.98, p=0.04). CONCLUSIONS: A catheter management protocol decreases the incidence of PPIVC in hospitalized patients. The risk of PPIVC increases for peripherally inserted central venous catheters when the patients have a history of phlebitis and for peripheral venous catheters when amiodarone or cefotaxime are infused. Catheterization of peripheral veins performed during morning shifts is associated with a lower incidence of PPIVC when compared with night shift catheterizations.