Claudio Ucciferri

Metabolic syndrome and cardiovascular risk in HIV-infected patients with lipodystrophy.

In this cross-sectional study, we evaluate potential predictors of Metabolic Syndrome (MS) in a group of 54 Caucasian chronically HIV-infected patients with lipodystrophy. According to ATP-III criteria, 22 patients were affected by MS and 32 were not. The mean age of the sample was 41.2 ± 8.6 years, and most patients were males (74.1%); the two groups were homogeneous for gender, age, viro-immunologic status and the duration of antiviral therapy. The independent association between MS and several factors including demographic characteristics, type of highly-active antiviral therapy (HAART), viro-immunologic response, common cardiovascular risk factors (including Framingham scores), and selected cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-18), was investigated using stepwise forward logistic regression. At multivariate analysis, the only independent predictors of the metabolic syndrome were triglycerides and IL-18. A10 mg/dL increase in triglycerides corresponds to an adjusted risk ratio for MS of 1.11 (95% IC: 1.04–1.19); and patients in the top tertile of IL-18 (those with IL-18 ≥ 530 pg/L) had more than three times the likelihood of MS, as compared to the bottom and medium fertiles of IL-18 (patients with IL-18 < 530 pg/L). This relationship was not attenuated by the inclusion of any other variable in the multivariate model. However, the association between metabolic syndrome and IL-18 is no longer significant when IL-18 is treated as a continuous variable (trend p = 0.087). Our results on HIV patients with lipodystrophy confirm previous findings on a strong independent association between IL-18 and MS in the general population. Further research is needed to clarify the mechanism of this association and its role in the development of cardiovascular disease in HIV patients.

Quorum sensing inhibitor FS3-coated vascular graft enhances daptomycin efficacy in a rat model of staphylococcal infection

The aim of the study was to investigate the efficacy of the quorum sensing inhibitor FS3 and daptomycin in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2×10(7) colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received: (i) intraperitoneal daptomycin, (ii) FS3-soacked graft, and (iii) daptomycin plus FS3-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS3 was coated to the surface of the prosthesis. The in vitro studies showed, that minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for daptomycin were lower in presence of FS3. In in vivo studies, when tested alone, daptomycin and FS3 showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. Daptomycin is an important candidate for prevention of staphylococcal biofilm related infection and FS3 could serve as an interesting anti-staphylococcal antibiotic enhancer.

Use of Epoetin Beta During Combination Therapy of Infection With Hepatitis C Virus With Ribavirin Improves a Sustained Viral Response

The aim of the study was to evaluate the effects of epoetin‐beta on anemia and sustained viral response in patients with chronic hepatitis C receiving treatment with pegylated interferon and ribavirin. Forty‐two Caucasian patients with chronic hepatitis C infection, treated with pegylated interferon α‐2a or α‐2b plus ribavirin, who experienced at least a 2 log decline in HCV‐RNA in the first month of therapy and a ≥2.5 g/dl hemoglobin drop from baseline, were recruited. They were divided into two groups: 22 patients received epoetin‐beta 30,000 U administered s.c. q.w. (group A) and 20 patients received a reduced ribavirin dose of 600 mg daily (group B). The end‐of‐treatment response was 95.4% (21/22) in group A and 80% (16/20) (P = 0.2) in group B. Sustained viral response in group A was 81.8% (18/22), statistically higher than in group B (45%, 9/20) (P = 0.03). Mean corpuscular volume of erythrocytes was statistically lower in group A than in group B 4 weeks after starting epoetin‐beta or reduced ribavirin dose (P < 0.001), end‐of‐treatment (P < 0.001) and after 6 months follow‐up (P < 0.001). A negative correlation between the levels of ferritin serum was found in group A at the baseline and mean corpuscular volume value after 1 month of combination antiviral therapy (r = −0.45; P = 0.35), 4 weeks after starting epoetin‐beta (r = −0.43; P = 0.04) and after 6 months follow‐up (r = −0.45; P = 0.03). Administration of epoetin‐beta increases sustained viral response rates among patients developing anemia, because the standard dose of ribavirin is maintained, thereby reducing the side‐effects of antiviral treatment. J. Med. Virol. 82:49–56, 2010.

Endothelial progenitor cell trafficking in human immunodeficiency virus-infected persons.

Objective:Human immunodeficiency virus (HIV)-infected people exhibit a high incidence of vascular diseases. Since in the general population the high cardiovascular risk has been associated with an impaired endothelial cell function, we investigated circulating endothelial progenitor cells in HIV-positive patients. Design:We evaluated circulating colony-forming unit–endothelial cell (CFU-EC) and endothelial colony-forming cell (ECFC) progenitors in 14 antiviral therapy-naive HIV-positive patients, in comparison with 15 normal controls. Methods:CFU-EC and ECFC derived from peripheral blood mononuclear cells from HIV-infected and HIV-uninfected individuals were recovered and evaluated for HIV genome presence by PCR. Vascular endothelial growth factor (VEGF) and apolipoprotein B mRNA-editing enzyme catalytic polypeptide like (APOBEC) subunits expression were evaluated in infected colonies by real-time PCR. Results:We found that circulating CFU-EC but not ECFC were significantly reduced in HIV-positive patients and that proviral HIV DNA was detectable only in CFU-EC but not in ECFC. Furthermore, the expression of APOBEC subunits was significantly lower in CFU-EC than in circulating monocytes. Accordingly, the CFU-EC displayed a high content of proviral DNA copies, suggesting that these cells have a high sensitivity to the HIV infection. Conclusions:Although HIV does not affect the ‘true endothelial progenitor’ compartment, it infects and strongly depletes circulating endothelial progenitors with hematopoietic signature. We unravel a novel pathogenetic mechanism by which HIV infection might cause vascular diseases.

Improved metabolic profile after switch to darunavir/ritonavir in HIV positive patients previously on protease inhibitor therapy.

Metabolic abnormalities associated with cumulative exposure to antiretroviral therapy have been linked to an increased risk of myocardial infarction in HIV positive individuals. The aim of this study was to evaluate whether the switch from lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) to darunavir/ritonavir (DRV/r) is able to improve the lipid profile. A total of 13 Caucasian subjects (7 from LPV/r and 6 from FPV/r) were enrolled in the study and received DRV/r at the dose of 800/100 mg, without change in their NRTI backbone. Viro‐immunological parameters, triglycerides (TGs), total cholesterol (TCh), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) cholesterol, fasting glucose, HOMA‐IR, indexes of hepatic and renal functionality, microalbuminuria and cystatin C were measured at baseline (T0), 3 months (T3), 6 months (T6), and 12 months (T12). The switch to DRV/r reduced levels of TCh, LDL, and TGs at T3. Similar improvements were confirmed further at T6 and at T12. A 14% increase in CD4+ count cells (P < 0.05) was observed. Serum cystatin C values showed a statistically significant decrease. After 12 months of switching to DRV/r from LPV/r or FPV/r, patients infected with HIV with TGs above 200 mg/dl, showed a 49% decrease in TGs, along with a 16% reduction of LDL and 19% reduction of TCh. Switching to DRV/r also improved immunological parameters, such as CD4+ cells count and cystatin C plasmatic levels, which may translate into a reduction of the cardiovascular risk. In conclusion, a switch to DRV/r should be considered in those HIV positive patients undergoing antiretroviral therapy, who also present abnormal lipid profiles. J. Med. Virol. 85:755–759, 2013.

Antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients.

BACKGROUND Hypertension is more prevalent among HIV-infected individuals than in the general population and contributes to increased cardiovascular risk. The angiotensin II receptor blocker telmisartan is also a partial peroxisome proliferator activated receptor-γ agonist with documented effects on glucose and lipid homeostasis. The aim of this study was to evaluate the antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients. METHODS A total of 18 HIV-positive men treated with antiretroviral therapy and recently diagnosed with hypertension were administered 80 mg telmisartan daily. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), viroimmunological and metabolic parameters, insulin resistance, C-reactive protein, microalbuminuria, cystatin C and plasma levels of interleukin-18 and endothelin-1 were measured at baseline (T0), 1 month (T1), 3 months (T3) and 6 months (T6). RESULTS Treatment with telmisartan not only decreased SBP and DBP levels, but also improved insulin resistance and microalbuminuria by T1. Levels of triglycerides significantly decreased and high-density lipoprotein cholesterol increased at T1, whereas total and low-density lipoprotein cholesterol levels were statistically reduced at T3 and T6. Cystatin C and endothelin-1 showed a significant reduction at T1, whereas interleukin-18 decreased at both T3 and T6. CONCLUSIONS Telmisartan was effective in reducing blood pressure and improving lipid metabolism and renal function. Reduction of endothelin-1 might be related to an endothelial protective effect. On the basis of these findings, and because of properties unrelated to blood pressure lowering, telmisartan might be the first choice antihypertensive drug for the treatment of HIV-positive patients.

Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis treated with linezolid

Linezolid is not yet recognized as a standard therapy for infective endocarditis but its use becomes a necessity when infection is due to multidrug-resistant microorganisms. This report describes 1 patient with endocarditis treated with linezolid and 45 similar cases from the medical literature.

Different strategies of 25OH vitamin D supplementation in HIV-positive subjects

Summary A high incidence of 25OH vitamin D deficiency has been observed in HIV-infected subjects. The objective of this study was to evaluate the effect of cholecalciferol administration on serum 25OH vitamin D levels in HIV-infected patients. This prospective cohort study included 153 HIV-positive subjects; 47 were treated with 300,000 IU intramuscular cholecalciferol, 67 with 25,000 IU oral cholecalciferol monthly, while the remaining 39 did not receive any treatment. The group treated orally had an increase of serum 25OH vitamin D concentration, changing from 15.7 ± 12.2 ng/mL to 27.4 ± 11.6 ng/mL after 10 months (T10). The group treated with intramuscular supplementation had an improvement, changing from 18.5 ± 10.5 ng/mL to 32.9.0 ± 12.2 ng/mL at T10. One-way repeated measures analysis of variance indicated a significant difference for 25OH vitamin D variation (p = 0.002) among the three groups. A significant effect of time (p < 0.001) and group × time interaction (p < 0.001) was found: at T10, 25OH vitamin D values were significantly higher in the oral and intramuscular groups with respect to the control group. Our findings showed that the supplementation with cholecalciferol in patients with HIV-infection improved 25OH vitamin D serum levels, and suggest that the two types of administration are equivalent, but are insufficient for severe forms of hypovitaminosis.

High Prevalence of Human Papillomavirus Type 58 in HIV infected men who have sex with men: A preliminary report in Central Italy

Human papillomavirus (HPV) infection and type‐specific prevalence at anal, oral, coronal sulcus, and urethral mucosa in fifty HIV positive men having sex with men (MSM) were evaluated; patients were enrolled in a non‐metropolitan area of Central Italy. Clinical and socio‐demographic information, drug, and sexual behaviors were obtained for each participant. HPV was detected by PCR from an overall of 200 specimens, and genotyping was performed by both Restriction Fragment Length Polymorphism analysis and sequencing.

Prevalence of anal, oral, penile and urethral Human Papillomavirus in HIV infected and HIV uninfected men who have sex with men

Aims of the study were to evaluate Human Papillomavirus (HPV) and type‐specific prevalence in four anatomical sites in HIV infected men who have sex with men (MSM) compared with HIV uninfected MSM. Participants were recruited among the attendees of Infectious Diseases Clinics in Central Italy. A trained medical practitioner collected by interview sociodemographic data and information on medical history, sexual behavior, and drug use. Swabs from anal canal, oral cavity, urethral mucosa, and coronal sulcus were tested for HPV DNA and genotyping. Ninety MSM were enrolled, 45 subjects within each group. Overall, 48.9% MSM were HPV positive and prevalence was higher in HIV infected men (60.0% vs 37.8%, P = 0.035). HPV at multiple anatomic sites occurred in 59.1% MSM, with 34.1% and 22.7% at two and three sites, respectively. Prevalence of anal, coronal sulcus, oral, and urethral HPV was 96.3%, 37%, 21.6%, and 18.5% in HIV infected MSM, and 70.6%, 70.6%, 29.4%, and 23.5% among HIV uninfected. A similar proportion of HIV infected and uninfected MSM (59.2% and 58.8%) carried at least one high‐risk genotype. Prevalence of types covered by nonavalent vaccine was 77.8% in HIV infected compared with 82.3% in HIV uninfected MSM. HPV 58 and 16 were mostly detected in HIV positive (43.7% and 31.2%) and negative MSM (50.0% and 40.0%). HPV detection rate underlined the high vulnerability of MSM to acquire multisite infections, characterized by various genotype combinations. Since nonavalent vaccine could have prevented 80% of HPV infections, study findings support the implementation of vaccination programs among MSM.