Fluvastatin showed anti-hepatitis C virus (HCV) activity in vitro, through the inhibition of geranylgeranylation of cellular proteins, and a synergistic effect with interferon (IFN)-alpha. Nevertheless statins up-regulate low-density lipoprotein (LDL) receptor, required for HCV cell entry, and the closely related scavenger receptors SRBI and CD36; moreover they reduce class II major histocompatibility complex expression on antigen presenting cell, modulating T-cell activation. In vivo LDL levels have been identified as prognostic indicator of sustained viral response to IFN in patients with HCV infection, suggesting that lipid-lowering agents might conversely favour HCV entry into the hepatocytes and translate into higher viral replication. We evaluated the effect of fluvastatin on HCV-RNA levels, CD36 expression and T-cell homeostasis in HCV-RNA positive patients. HCV-RNA was measured at baseline and after 4 weeks in 42 HCV/HIV-1 co-infected patients, randomized to receive either fluvastatin 80 mg qd or no treatment. CD36 expression and markers of T-cell activation were evaluated by means of flow cytometry. Plasma interleukin (IL)-10, IFN-gamma and IL-7 were measured by ELISA. Serum cholesterol and LDL decreased significantly in the treatment group (P = 0.0001 and 0.01, respectively). Surprisingly a significant increase of HCV-RNA levels was seen after 4 weeks of fluvastatin (P = 0.03). The percentages of naive/activated/apoptotic cells and CD36 expression remained unchanged. Fluvastatin did not inhibit HCV-RNA replication in vivo; conversely we observed a significant increase of HCV-RNA levels. CD36 expression on monocytes were not up-regulated by statins as previously reported in vitro. The correlation between HCV infectivity, oxidized-LDL receptor and statins in HCV infection need further evaluation.
The emergence, in our study, of a correlation between the percentage of CD8+/CD38+/RO+ T cells (well established markers of progression to AIDS independently of CD4+ T lymphocytes) and positive FDG-PET in ART-naive patients is a novel finding that seems to confer prognostic value on FDG uptake. FDG uptake is strongly associated with response to ART independently of a previous AIDS diagnosis. Notably, no differences were observed between ART-treated subjects classed as immunological responders and those classed as non responders. Data herewith indicate that FDG uptake and immunological variables are unrelated when ART is being administered. This is evidence of the complementarity of immunological and FDG measures. FDG uptake is a sensitive marker of disease state and its relation with CD8+/CD38+/CD45RO+ T cells indicates that it can be considered a marker of disease status. The lack of a correlation between FDG uptake and immunological variables in patients under ART warrants further investigation.
Fluvastatin addition to standard therapy did not significantly increase the SVR rate in HIV/HCV genotype 1 co-infected patients; however, it did significantly improve the RVR. Further studies are needed to confirm these promising results and to investigate the mechanisms of action of statins in HCV infection.
Mycobacterium lentiflavum is a recently described nontuberculous mycobacterium that has mainly clinical importance in young children with cervical lymphadenitis and in immunocompromised patients. We describe a case of chronic pulmonary infection in an immunocompetent patient. Our observation confirms clinical, diagnostic, and treatment difficulties in the management of M. lentiflavum infection.
An immune response mediated by type 2 cytokines is thought to contribute to the development and unfavorable outcome of aspergillosis. Adjuvant therapy with interferon-gamma (IFN-gamma) and granulocyte-macrophage colony stimulating factor (GM-CSF) was added to antifungal treatment in three nonneutropenic patients (one HIV-positive and two HIV-negative patients) with culture proven aspergillosis refractory to classical antifungal therapy. Clinical improvement was observed concomitantly with an increase in peripheral blood leukocyte proliferation and type 1 cytokines production. Our findings suggest an association between the improvement in type 1 cytokine production observed during IFN-gamma and GM-CSF administration and a better control of Aspergillus infection in patients with progressive disease despite adequate antifungal therapy.
We investigated the effect of antioxidant supplementation on mitochondrial function, fat distribution, and lipid and glucose metabolism in HIV-1-infected patients with antiretroviral therapy (ART)-related lipoatrophy. 61 ART-treated HIV-1-infected patients with lipoatrophy were randomized to receive either n-acetyl-L-carnitine (n = 21), lipoic acid + n-acetylcisteine (LA/NAC) (n = 20), or no supplementation (n = 20) for 48 weeks. At baseline and at the end of treatment, mitochondrial function was studied by (13)C-methionine breath test and by mitochondrial (mt)-DNA quantification on circulating T-cells and subcutaneous adipose tissue. Body composition was assessed by dual-energy X-ray absorpiometry (DEXA). (13)CO(2)-exhalation increased between baseline and week 48 in both supplementation arms as evidenced by a higher delta over baseline excretion at 45 min (from mean ± SEM of 7.8 ± 1.08 to 9.9 ± 0.6, p = 0.04 in the n-acetyl-carnitine arm, and from 7.4 ± 0.8 to 11.5 ± 1.6, p = 0.01 in LA/NAC arm). Cumulative (13)CO2 excretion increased from median (interquartile range; IQR) of 3.25 (2.55-4.2) to 4.51 (4.12-5.2) in the carnitine arm; from 3.79 (2.67-4.37) to 4.83 (4.25-5.56) in the LA/NAC arm; p = 0.004, 0.02, respectively. mtDNA content increased in CD4+ T-cells from patients who received n-acetyl-carnitine (+30 copies/cell; p = 0.03), without significant difference by the overall comparison of the study groups. Fat body mass and lipid profile did not change significantly in any of the arms. Our study showed that antioxidant supplementation may have a protective role on mitochondrial function, with limited effects on the reversal of clinical lipodystrophic abnormalities in HIV-1-infected patients.
Idiopathic noncirrhotic portal hypertension (NCPH) is an infrequent but possibly underestimated cryptogenetic liver disease recently described in small series of HIV-infected patients. The exposure to antiretroviral drugs, a direct role of HIV itself, microbial translocation from the gut, or a thrombophilic propensity have been suggested as possible pathogenic mechanisms. In this case control study, we describe 11 HIV-infected patients with idiopathic NCPH and compare the activity of protein C and S, and soluble CD14 levels (a surrogate marker of the translocation of intestinal bacterial products) with 10 age- and gender-matched HIV-infected controls with no liver disease. The clinical presentation of the 11 patients with NCPH was characterised by acute variceal bleeding (2/11), ascites (2/11), portal thrombosis (2/11), and ultrasonographic and endoscopic signs of portal hypertension (11/11), with slightly high alanine transaminase (ALT) and γglutamyl transpeptidase (γ-GT) levels. The FibroScan median liver stiffness was 8.1 kPa, which is inconsistent with significant fibrosis, and nodular regenerative hyperplasia was diagnosed in the 5 patients who underwent liver biopsy. The NCPH patients showed no impairment of hepatic synthesis, but had lower serum albumin levels and a higher international normalized ratio (INR) than the controls (p = 0.01), and lower protein C and S activity, although within the normal range (p = 0.02 and 0.3, respectively). No significant difference in soluble CD14 was seen between the two groups. In conclusion, the etiology of NCHP is not still established, but in order to prevent the dramatic complications of portal hypertension, all HIV-infected patients with unexplained liver enzyme abnormalities or thrombocytopenia should be considered for further investigations by means of thrombophilic screening, Doppler ultrasound evaluation, and in the presence of portal hypertension, endoscopy and liver biopsy.
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