Maddalena Casana

Insulin resistance affects early virologic response in HIV-infected subjects treated for hepatitis C infection.

To the Editor: The use of highly active antiretroviral therapy (HAART) has been associated with an increased frequency of insulin resistance (IR) and of its clinical correlates, such as glucose intolerance and type-2 diabetes. A direct role of protease inhibitors (PIs) has been proposed; however, traditional risk factors for IR other than HIV infection and HAART use may also predict glucose intolerance or type-2 diabetes in HIVinfected population. In the general population, a correlation between hepatitis C virus (HCV) infection and IR has been demonstrated; the possible mechanisms at the basis of this finding seem to be increased tumor necrosis factor (TNF) production, together with the enhancement of suppressor cytokines (SOC-3), both blocking PI3K and Akt phosphorylation. In HIVnegative patients with chronic HCV receiving pegylated interferon plus ribavirin, IR, as measured by the hemostatic model of assessment (HOMA) index, has been related to the 6-month virologic response. In addition, subjects with a sustained virologic response had lower HOMA values compared with others. Whether IR represents a marker of difficult-to-cure subjects or whether it acts through a pathogenic mechanism by blocking the antiviral activity of interferon is unknown. HCV infection is often a comorbidity in HIV-infected subjects, especially if they are intravenous drug abusers. It has often been associated with IR and hyperglycemia in HIVinfected patients receiving HAART. At the moment, few data are available on the role of IR in influencing the virologic response to anti-HCV treatment in the HIV-infected population. The aim of this study is to evaluate the correlation between IR and early virologic response (EVR) in HIV/HCVcoinfected subjects receiving pegylated interferon plus ribavirin. We included in this study 29 consecutive HIV-infected subjects followed at our clinic who started an antiHCV treatment with pegylated interferon a-2a plus ribavirin (at a dosage of 1000 to 1200 mg according to body weight) in January 2006. The following variables were collected at baseline (time of starting anti-HCV treatment): gender, age, race, body mass index (BMI), platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum glucose, insulin, total cholesterol, triglycerides, CD4 cell count, HIV RNA level, HCV RNA level, HCV genotype, and use of HAART (defined as use of

Hepatitis C management in prisons: An insight into daily clinical practice in three major Italian correctional houses.

2 nucleoside reverse transcriptase inhibitors with any PI or nonnucleoside reverse transcriptase inhibitors). Serum insulin levels were measured by electrochemiluminescence immunoassay using an autoanalyser (Elecsys 1010/2010; Elecsys Modular Analytics E170; Roche, Basel, Switzerland). HIV-RNA load was assessed using the reverse transcriptase (RT) polymerase chain reaction (PCR), with a detection limit <60 copies/mL (Arthus Qiagen, Heiden, Germany). Qualitative PCR analysis for HCV was performed by nested PCR (Amplicor Roche, Basel, Switzerland; detection limit <15 IU/L). HCV genotyping was performed using a line-probe assay (INNOLiPA HCV II; Immunogenetics, Belgium). IR was calculated through the HOMA equation: fasting insulin (mIU/L) 3 fasting glucose (mmol/L)/22.5. IR was defined as a HOMAvalue >3.8, according to other studies on white populations with low risk for diabetes. EVR was defined as HCV RNA level <15 IU/mL after 3 months of anti-HCV treatment; additionally, we evaluated the rapid virologic response (RVR), defined as HCV RNA level <15 IU/L after 1 month of anti-HCV treatment. Differences between variables were calculated using the x and Student t tests when appropriate. Table 1 shows the demographics and clinical characteristics of the subjects included in our study according to the HOMA values at baseline. All the patients were white. Ten subjects (34.5%) had a HOMA index >3.8, and 19 (65.5%) had values #3.8. No statistically significant differences were observed in the 2 groups according to the variables considered. After 3 months of anti-HCV treatment, median AST and ALT levels decreased in both groups. In subjects with IR at baseline, median AST and ALT levels decreased from 109 (interquartile range [IQR]: 60 to 141) IU/ L to 54 (IQR: 42 to 65) IU/L (P < 0.01) and from 105 (IQR: 76 to 124) IU/L to 53 (IQR: 45 to 88) IU/L (P < 0.01), whereas in subjects without IR, AST and ALT levels decreased from 108 (IQR: 61 to 147) IU/L to 37 (IQR: 30 to 50) IU/L (P < 0.01) and from 101 (IQR: 68 to 109) IU/L to 33 (IQR: 27 to 48) IU/L (P < 0.01), respectively. RVR was achieved in 8 (42.1%) of 19 subjects without IR and in 0 of 10 with IR at baseline (P < 0.001); EVR was observed in 16 (84.2%) of 19 subjects without IR and in 0 of 10 with IR (P < 0.001). The 3 subjects who did not achieve EVR had genotype 1a, 3a, and 4c/4d, respectively. HCV infection and HAART are conditions associated with a higher probability of developing IR. Such a condition is a known predictor of reduced sustained virologic response to anti-HCV treatment in HCV-infected subjects. Conversely, the achievement of RVR and EVR is a strong predictor of recovery from HCV infection; therefore, subjects who do not achieve this endpoint may be discontinued from anti-HCV treatment because of a low probability of sustained virologic response. In the present study, including only HIV/HCV-coinfected subjects, we found that subjects without IR at baseline are more likely to reach RVR and EVR than the others. Also, in subjects with genotype 3, which is known to respond better to anti-HCV treatments, the presence of IR does not allow for the achievement of RVR or EVR. These results, obtained on a limited number of subjects, suggest that IR should always be evaluated before starting anti-HCV treatment. Therefore, the correction of IR, and the consequent recovery of insulin sensitivity, could improve RVR and EVR in the HIV/ HCV-coinfected population treated with pegylated interferon and ribavirin, and

Non-invasive markers of liver fibrosis in HCV mono-infected and in HIV/HCV co-infected subjects.

1) Wong VW, Wong GL, Yeung JC, Fung CY, Chan JK, Chang ZH, et al. Long-term clinical outcomes after fatty liver screening in patients undergoing coronary angiogram: a prospective cohort study. HEPATOLOGY 2016;63:754-763. 2) Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. HEPA-

Abacavir and Cardiovascular Risk in HIV-Infected Patients: Does T Lymphocyte Hyperactivation Exert a Pathogenic Role?

Non-invasive markers of liver fibrosis have been recently developed as a possible alternative to liver biopsy. The clinical management of hepatic diseases is dependent on the extent of liver fibrosis. Liver biopsy remains the gold standard but severe complications are found in about 0.5% of cases. Studies involving sequential liver biopsies are impractical, costly, and risky. Therefore non-invasive markers of liver fibrosis could be useful. These drawbacks justify an intensive research on non-invasive alternatives. Several serum markers are either directly involved in fibrosis remodelling or are indirectly associated with the presence of significant liver fibrosis. More recently, fibrosis scores calculated from statistical models have been described. This review describes the role of non-invasive markers in assessing hepatic fibrosis in both HCV mono-infected and HIV/HCV co-infected subjects.

Hepatitis B vaccination in HIV-infected subjects.

Purpose of the study The association between abacavir exposure and cardiovascular disease (CVD) in HIV-infected patients is currently intensely debated. Recently, the D:A:D Study Group described increased myocardial infarction risk in patients with current/recent abacavir exposure, while repository data from GlaxoSmithKline clinical trials failed to find any association. Given the association between lymphocyte hyperactivation and CVD, and the major role of T-cell hyperactivation in HIV/AIDS, the purpose of our study was to investigate T-cell immunephenotype and proinflammatory cytokines kinetics in HIV-infected patients receiving abacavir-containing regimens.

Predictors of severe hyperbiliruniaemia in HIV-infected patients treated with atazanavir (ATV)

Subjects at risk of infection with human immunodeficiency virus (HIV) are also at high risk of acute and chronic hepatitis B virus (HBV) infection. HIV is associated with higher HBV viraemia and with the risk of HBV reactivation, chronic active HBV infection, cirrhosis and death. Therefore, hepatitis B vaccination is recommended for all HIV-infected subjects lacking prior immunity. However, the immune response to hepatitis B vaccine is frequently suboptimal in this population. High CD4+ cell counts and low HIV viraemia are well known factors associated with a better rate of response. Moreover, higher hepatitis B vaccine doses and/or prolongation of the vaccination schedule, as implemented for patients with immune deficiencies other than HIV, may be considered. New vaccination cycles should be considered if post-vaccination titers of antibodies to hepatitis B surface antigen are < 10 mIU/mL (< 10 UI/L). The immunization of all young and middle-aged adults appears to be the most useful strategy to protect all patient-populations at high risk of sexually transmitted diseases.

Correlates of spinal deforming index (SDI) in HIV-positive patients naive and on treatment

Methods HIV-infected subjects on ATV/ritonavir containing stable HAART regimen were included. ATV plasma concentrations were measured 24 hours after the last dose by HPLC with UV detector. Polymorphism at the uridin-glocoronosyl-transferase 1A1 (UGT1A1) was examined in DNA extracted from blood mononuclear cells, to identify subjects with Gilberts syndrome. The correlation between bilirubin plasma levels, ATV concentration and polymorphism of UGT1A1 (defined as the presence than at least one TA7 allele) were evaluated by multivariate linear regression (other covariates included: gender, age, CD4 count, months of ATV exposure). Predictors of severe hyperbilirubinemia (>2.5 μmol/l; grade 3) were evaluated by multivariate logistic regression (polymorphism at UGT1A1, Cmin, BMI, age included as covariates).

Carotid intima media thickness with no cardiovascular disease in HIV-infected patients correlates with a hyperactivated/pro-apoptotic T-cell phenotype

Methods HIV-infected subjects naive or on stable HAART were included. Vertebral deformities were identified using SDI (according to semiquantitative method by Genant), calculated by summing the deformity grades of all vertebrae (T4 to L4); pathological deformities are defined as follow: grade 1 between 20–25%, grade 2 between 26–40%, and grade 3 > >40%. According to WHO criteria, osteopenia and osteoporosis were diagnosed in patients having spine BMD calculated as -1 << T-score << -2.5 and T-score ≤≤2.5, respectively. The correlation between SDI and spine BMD was evaluated by univariate and multivariate linear regression. [Other variables considered: gender, age, current CD4 count, CD4 nadir, BMI, lipid parameters, alcohol intake, smoking habit, physical activity, family history for bone fracture, months of ARV exposure, and co-infection with hepatitis viruses; only the variables with p <<0.2 in univariate analyses were included in the final model.]

Sudden Cardiac Death in a Young HIV-Positive Man on Effective Antiretroviral Therapy

Background HIV-infected patients may be at increased risk of cardiovascular disease (CVD), and present higher carotid intima media thickness (IMT) compared with healthy controls. Besides clinical and metabolic factors, atherosclerosis in HIV is influenced by immune and inflammatory parameters. Given that T-cell activation correlates with CVD and HIV accounts for heightened T-cell hyperactivation, we hypothesized that early IMT increases associate to T-cell hyperactivation.

Subclinical hypothyroidism in HIV-infected subjects

We describe the case of a young HIV-positive man on effective HAART with excellent viro-immunological control who presented a massive cardiac infarction. Despite the presence of clinical risk factors for cardiovascular disease, the patient had normal arterial carotid IMT values, known to be strong predictors of atherosclerosis and stroke. Interestingly, parameters of T-cell activation (CD8+CD38+) were shown to increase just before the onset of myocardial infarction. As T-cell activation is known to mediate atherosclerosis, the authors suggest that surrogate immunologic markers should be identified to better assess cardiovascular risk in the setting of HIV infection.