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Biomedical subjects

Raffaele Bruno

Publications and source records attributed to Raffaele Bruno.

16 recordsLinked to original sources

Overview on the incidence and the characteristics of HIV-related opportunistic infections and neoplasms of the heart: impact of highly active antiretroviral therapy.

The manifestation of cardiac involvement in the course of HIV infection has been significantly changed since the introduction of highly active antiretroviral therapy. While in the pre-highly active antiretroviral therapy era the predominant cardiac pathology was represented by localization of opportunistic infection, now new forms of heart involvement are described. Among infectious agents, viruses and bacteria caused the majority of infections. The 'classic' opportunistic agents, such as Toxoplasma, non-tuberculous mycobacteria, cytomegalovirus and Cryptococcus, have virtually disappeared. Endocarditis is still the most frequent infectious disease of the heart in HIV-infected patients, occurring mainly in drug users, and with the improvement in prognosis, the need for cardiac surgery is increasing. Tuberculosis, the incidence of which is still high in poor resources settings where antiretroviral drugs are not available, is a frequent cause of pericarditis, frequently evolving into cardiac tamponade. Recent studies suggest the direct role of HIV as the cause of myocarditis and heart vessel pathology. This finding points out the need of improving our knowledge about the pathogenesis, diagnosis and treatment of this kind of complication.

AIDS-Related Opportunistic Infections↗

Hypertension among HIV patients: prevalence and relationships to insulin resistance and metabolic syndrome.

OBJECTIVES: Metabolic syndrome is a cluster of risk factors, such as central obesity, dyslipidemia, glucose intolerance, hypertension, related to insulin resistance. In HIV patients insulin resistance and several metabolic abnormalities of the metabolic syndrome have been described, but few and conflicting studies have investigated the behaviour of blood pressure. The aims of the present study were to evaluate the prevalence of hypertension in a large group of HIV-patients on highly active antiretroviral therapy (HAART) and to investigate the relationship between hypertension, metabolic syndrome and insulin resistance. DESIGN: Case control study. METHODS: We enrolled 287 HIV-positive patients on HAART (mean age 41.1 +/- 7.5 years) and 287 age- and sex-matched controls. Insulin resistance was estimated by the homeostasis model insulin resistance assessment (HOMA) index. Metabolic syndrome was defined according to the European Group for the Study of Insulin Resistance. RESULTS: HIV patients showed a prevalence of subjects with hypertension (34.2 versus 11.9%; P < 0.0001) and metabolic syndrome (33.1 versus 2.4%; P < 0.0001) higher than controls. HOMA was higher in HIV-patients than controls (3.3 +/- 1.2 versus 2.0 +/- 0.9; P < 0.0001). HOMA (3.7 +/- 1.0 versus 3.1 +/- 1.2; P < 0.001) and the prevalence of subjects with the metabolic syndrome (64.3 versus 16.9%; P < 0.0001) were greater in HIV-patients with than in those without hypertension. Multiple logistic regression analysis showed that family history of hypertension (odds ratio [(OR): 8.73; 95% confidence interval (CI): 4.31-17.70; P < 0.0001], metabolic syndrome (OR: 6.79; 95% CI: 3.27-14.10; P < 0.0001), lipodystrophy (OR: 4.80; 95% CI: 2.43-9.85; P < 0.0001) and HOMA (OR: 4.13; 95% CI: 1.14-14.91; P < 0.05) were predictors of hypertension in HIV-patients. CONCLUSIONS: The present study shows that hypertension is frequent in HIV patients on HAART and that hypertension appears to be linked to insulin resistance; in particular, hypertension seems to be a part of the metabolic syndrome.

Adult↗

Fast relapse and high drop out rate of 48 weeks daily interferon monotherapy in HIV-infected patients with chronic hepatitis C.

BACKGROUND: The standard of care for HCV Hepatitis is the combination of interferon (IFN) plus Ribavirin. In HIV patients the use of this combination therapy may induce drug interactions, and reduces the adherence to HAART. The aim of this study is to evaluate safety and efficacy of a 48 weeks daily dose IFN schedule. METHODS: We evaluated 50 coinfected patients; alpha IFN 2a was administered at a dose of 3 MU daily. The baseline values were the following : CD4+ 515 cells/mmc (mean); HIV-RNA <50 copies/ml in all patients; HCV-RNA 28, 3 x 106 copies/ml. RESULTS: At 48 weeks, 10 patients (20%) achieved a biochemical and virological response according to an intention to treat analysis.Twenty four patients (48%) underwent a drop-out mainly by side effects related to overlapping toxicity of interferon and antiretroviral therapy. All the patients, who responded to the treatment, showed a fast relapse one month after the end of treatment. CONCLUSION: Although our results demonstrated a very poor outcome and a bad tolerance to interferon monotherapy, this approach should not be dropped out, mainly in patients at high risk for side effects and in those with cirrhosis who do not tolerate or are at increased risk for the use of ribavirin.

Antiviral Agents↗

HCV chronic hepatitis in patients with HIV: clinical management issues.

HIV-hepatitis C virus (HCV) coinfection is common and affects more than one-third of all HIV infected persons worldwide. Prevalence among risk categories varies according to shared risk factors for transmission, mainly intravenous drug use (IDU) and hemophiliacs. Chronic HCV infection seems to accelerate the course of HIV disease, resulting in a worsened clinical and immunological progression. At the same time, several studies suggest that HIV disease modifies the natural history of HCV infection, leading to a faster course of progression from active hepatitis to cirrhosis, to end stage liver disease and death. HCV infection mimics opportunistic diseases because its natural history is significantly accelerated in HIV patients. Since highly active antiretroviral therapy (HAART) has slowed the progression of HIV disease and decreased the rate of HIV associated mortality, the prognosis of HIV disease has been modified, and the need to treat HCV coinfection become a significant issue. Because of the poor response rate obtained by either interferon alone or interferon thrice weekly plus ribavirin, the combination of pegylated interferon and ribavirin will probably become the standard of care, although the clinicians should be aware of the overlapping toxicity of nucleoside analogues and ribavirin. Many selected categories of patients pose particular challenges to physicians treating HCV infection: nonresponders to interferon, cirrhotic patients, and patients infected with both HCV and HBV. Liver transplantation in HIV patients is currently under evaluation, but should become the rescue therapy for HIV patients with end stage liver disease.

Anti-HIV Agents↗

Distinct mutational drug resistance profiles of HIV-1 RNA in plasma and culture isolates of patients receiving antiretroviral therapy.

The differences in profiles of HIV mutational drug resistance between paired plasma samples and culture isolates were analyzed in treated and untreated HIV-infected patients. The DNA sequence of the entire protease gene and codons 1-320 of the reverse transcriptase gene was analyzed from the paired plasma samples and viral isolates. Differences in the distribution of resistance mutations from the two sources were detected in 13 of 14 patients receiving antiretroviral therapy. Some excess mutations, observed in plasma samples but not in culture isolates, are reportedly associated with resistance to antiretroviral drugs. These results emphasize the need for standardization and clinical laboratory use of phenotypic assays that avoid extensive cocultivation.

Antiretroviral Therapy, Highly Active↗

Evaluation of the risk factors associated with lipodystrophy development in a cohort of HIV-positive patients.

The prevalence of lipodystrophy in an HIV-infected population and the risk factors associated with body shape changes were analysed in this study. Five hundred and four subjects were included. Among these, 201 (39.9%) had features of lipodystrophy syndrome (cases); 303 (60.1%) constituted the control group. Compared with the control group, the lipodystrophy subjects were different in age (P = 0.01); duration of antiretroviral therapy (P < 0.001); length of exposure to nucleoside reverse transcriptase inhibitors (NRTIs) (P < 0.001) and to protease inhibitors (P < 0.001); nadir of CD4 cell count (P < 0.001); and value of plasma HIV-RNA before antiretroviral therapy (P = 0.008). In a multivariate analysis, length of therapy and a nadir CD4 cell count below 250 cell/microl were associated with an increased risk of lipodystrophy. Among patients with lipodystrophy, isolated fat loss was observed in 46 (23%); isolated fat accumulation in 40 (20%); mixed (loss and accumulation) syndrome in 50 (25%); and isolated metabolic changes in 65 (32%). Subjects with morphological alterations displayed a greater cumulative time of exposure to NRTIs and to protease inhibitors than patients with isolated metabolic alterations. Patients with lipoatrophy had had a greater exposure to stavudine.

Adolescent↗

Clinical experiences with interferon as monotherapy or in combination with ribavirin in patients co-infected with HIV and HCV.

Human immunodeficiency virus (HIV) co-infection accelerates progression of hepatitis C virus (HCV) toward cirrhosis. Thus, with the increase of life expectancy observed after introduction of combination antiretroviral treatment, liver disease is becoming an increasing cause of morbidity and mortality in HIV-infected patients. In addition, HCV co-infection blunts CD4 restoration induced by HAART and increases HAART hepatotoxicity. For all these reasons, anti-HCV treatment is mandatory in HIV seropositives. The perfect treatment of hepatitis C should not only be safe and effective, but it should not have any adverse impact on HIV diseases and concurrent anti-HIV therapy. Two drugs are currently licensed for treatment of HCV: interferon alfa (IFNalpha) and ribavirin. Three hundred and thirty-eight patients have been included in pilot studies on the efficacy and tolerability of IFNalpha monotherapy: 16% showed sustained response and 10% dropped out. No significant adverse impact of IFNalpha monotherapy on HIV diseases or antiretroviral treatment has been observed. IFNalpha and ribavirin in combination have been introduced more recently: only 88 patients were included in pilot studies published as full papers with a 25% sustained response and an 11% rate of drop outs. Anemia and cumulative toxicity with didanosine were the most important side effects of combination treatment, but it did not affect HIV disease progression. Higher rates of sustained response (33%) without increase of side effects have been observed in preliminary experiences with the new long-acting pegylated interferons in combination with ribavirin. The search for the perfect treatment continues.

Drug Therapy, Combination↗

Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects.

Shared epidemiological risks have resulted in HIV-infected populations having a high prevalence of hepatitis B virus (HBV) co-infection. Several prospective studies have investigated the impact of HBV co-infection on HIV disease progression; most of them were negative. On the contrary, there is evidence that HIV may modify the natural history of HBV infection. HIV positive subjects have higher rates of HBV chronification, higher HBV replication, lower ALT levels and lower rates of seroconversion to anti-HBe and anti-HBs. The impact of HIV co-infection on the outcome of HBV infection is still controversial, even if some studies have shown an accelerated progression towards decompensated cirrhosis in HIV co-infected subjects. HBV co-infection is a risk factor for severe hepatotoxicity during HAART. Vaccination for HBV is mandatory in nonimmune HIV subjects, however its efficacy in immunosuppressed patients is still controversial. HIV co-infection decreases the effectiveness of Interferon in the treatment of HBV infection. Because of its activity against both HBV and HIV, lamivudine is used in HIV-HBV co-infected patients at doses of 300 mg/daily and as part of an antiretroviral regimen, but the rate of sustained response is poor and HBV strains with mutations associated with lamivudine resistance occur at a rate of 20% per year. Trials of new drugs with activity against HBV, some of them with activity also against HIV, and some of them without cross-resistance with lamivudine, are now underway. Highly Active Anti-Hepatitis B Therapy will probably soon come of age.

Adult↗