Multidrug-resistant tuberculosis outbreak in an Italian prison: Tolerance of pyrazinamide plus levofloxacin prophylaxis and serial interferon gamma release assays

The optimal treatment for latent tuberculosis infection (LTBI) in subjects exposed to multidrug-resistant (MDR) tuberculosis (TB) remains unclear, and the change in response of the QuantiFERON-TB Gold In-Tube (QTB-IT) test during and after treatment is unknown. Between May 2010 and August 2010, 39 prisoners at the 'Casa Circondariale' of Modena, Italy, were exposed to a patient with active pulmonary MDR TB. All contacts were tested with the tuberculin skin test and QTB-IT. Upon exclusion of active TB, subjects positive to both tests were offered 6 months' treatment with pyrazinamide (PZA) and levofloxacin (LVX). QTB-IT testing was repeated at 3 and 6 months after initial testing in all subjects who were offered LTBI treatment. Seventeen (43.5%) of 39 subjects tested positive to both tuberculin skin test and QTB-IT test, and 12 (70.5%) agreed to receive therapy with PZA and LVX at standard doses. Only five (41.6%) of 12 subjects completed 6 months' treatment. Reasons for discontinuation were asymptomatic hepatitis, gastritis and diarrhoea. The QTB-IT values decreased in all subjects who completed the treatment, in two (33%) of six of those who received treatment for less than 3 months and in one (50%) of two patients who discontinued therapy after 3 months. The QTB-IT test results never turned negative. Despite the small number of subjects, the study confirmed that PZA plus LVX is a poorly tolerated option for MDR LTBI treatment. We observed a large degree of variation in the results of the QTB-IT test results among participants. The study confirmed that the interferon gamma release assay is not a reliable tool for monitoring the treatment of MDR LTBI in clinical practice

Combined Use of Waist and Hip Circumference to Identify Abdominally Obese HIV-Infected Patients at Increased Health Risk

OBJECTIVES: To determine whether for a given waist circumference (WC), a larger hip circumference (HC) was associated with a reduced risk of insulin resistance, type 2 diabetes (T2D), hypertension and cardiovascular disease (CVD) in HIV-infected patients. A second objective was to determine whether, for a given WC, the addition of HC improved upon estimates of abdominal adiposity, in particular visceral adipose tissue (VAT), compared to those obtained by WC alone. METHODS: HIV-infected men (N\u200a=\u200a1481) and women (N\u200a=\u200a841) were recruited between 2005 and 2009. WC and HC were obtained using standard techniques and abdominal adiposity was measured using computed tomography. RESULTS: After control for WC and covariates, HC was negatively associated with risk of insulin resistance (p<0.05) and T2D [Men: OR\u200a=\u200a0.91 (95% CI: 0.86-0.96); Women: OR\u200a=\u200a0.91 (95% CI: 0.84-0.98)]. For a given WC, HC was also negatively associated with a lower risk of hypertension (p<0.05) and CVD [OR\u200a=\u200a0.94 (95% CI: 0.88-0.99)] in men, but not women. Although HC was negatively associated with VAT in men and women after control for WC (p<0.05), the addition of HC did not substantially improve upon the prediction of VAT compared to WC alone. CONCLUSIONS: The identification of HIV-infected individuals at increased health risk by WC alone is substantially improved by the addition of HC. Estimates of visceral adipose tissue by WC are not substantially improved by the addition of HC and thus variation in visceral adiposity may not be the conduit by which HC identifies increased health risk

Hepatocellular Carcinoma in HIV-infected Patients: Check Ealy, Treat Hard

Purpose. Hepatocellular carcinoma (HCC) is an increasingcause of mortality in HIV-infected patients inthe highly active antiretroviral therapy (HAART) era.The aims of this study were to describe HCC tumorcharacteristics and different therapeutic approaches, toevaluate patient survival time from HCC diagnosis, andto identify clinical prognostic predictors in patients withand without HIV infection.Patients and Methods. A multicenter observationalretrospective comparison of 104 HIV-infected patientsand 484 uninfected patients was performed in four Italiancenters. HCC was staged according to the BarcelonaClinic Liver Cancer (BCLC) criteria.Results. Tumor characteristics of patients with andwithout HIV were significantly different for age, EasternCooperative Oncology Group performance status(PS) score <1, and etiology of chronic liver disease. Despitethe similar potentially curative option rate and better BCLC stage at diagnosis, the median survivaltime was significantly shorter in HIV patients. HIVpatients were less frequently retreated at relapse.Independent predictors of survival were: BCLC stage,potentially effective HCC therapy, tumor dimension <3cm, HCC diagnosis under a screening program, HCC recurrence,and portal vein thrombosis. Restricting the analysisto HIV patients only, all positive prognostic factorswere confirmed together with HAART exposure.Conclusion. This study confirms a significantlyshorter survival time in HIV HCC patients. The lessaggressive retreatment at recurrence approach does notbalance the benefit of younger age and better BCLCstage and PS score of HIV patients. Thus, consideringthe prognosis of HIV HCC patients, effective screeningtechniques, programs, and specific managementguidelines are urgently needed

Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p &lt; 0.001), M133I (20.6% vs. 3.9%, p &lt; 0.001), and Q181E (11.8% vs. 0.6%, p &lt; 0.001). By multivariable analysis, the presence of &gt;1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p &lt; 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

Combined use of waist and hip circumference to identify abdominally obese HIV-infected patients at increased health risk.

ObjectivesTo determine whether for a given waist circumference (WC), a larger hip circumference (HC) was associated with a reduced risk of insulin resistance, type 2 diabetes (T2D), hypertension and cardiovascular disease (CVD) in HIV-infected patients. A second objective was to determine whether, for a given WC, the addition of HC improved upon estimates of abdominal adiposity, in particular visceral adipose tissue (VAT), compared to those obtained by WC alone.MethodsHIV-infected men (N = 1481) and women (N = 841) were recruited between 2005 and 2009. WC and HC were obtained using standard techniques and abdominal adiposity was measured using computed tomography.ResultsAfter control for WC and covariates, HC was negatively associated with risk of insulin resistance (pConclusionsThe identification of HIV-infected individuals at increased health risk by WC alone is substantially improved by the addition of HC. Estimates of visceral adipose tissue by WC are not substantially improved by the addition of HC and thus variation in visceral adiposity may not be the conduit by which HC identifies increased health risk

Vitamin D3 supplementation decreases the risk of diabetes mellitus among patients with HIV infection.

Type 2 diabetes mellitus (DM), insulin resistance and hypovitaminosis D are common among individuals living with HIV. Low vitamin D (VitD) has been associated with insulin resistance and DM in the general population and more recently in the HIV infected population. Our objective was to examine if the use of VitD3 supplementation could prevent the development of DM among patients with HIV infection