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Biomedical subjects

Roberto Manfredi

Publications and source records attributed to Roberto Manfredi.

At least 73 records · Page 4Linked to original sources

Immigration, HIV infection, and antiretroviral therapy in Italy. An epidemiological and clinical survey.

Epidemiological, clinical, and therapeutic features of 77 consecutive HIV-infected non-European Union immigrants were compared according to gender. Immigrants (from Sub-Saharan Africa in around 60% of cases) represented 7.9% of our patient cohort at the end of 2002. Compared with male patients, females were more numerous, significantly younger (p.0001), and experienced sexual exposure versus drug addiction (p.02), while no difference was observed according to place of origin. A negative HIV serology preceding immigration was available for five women and four males only, while HIV disease was known before migration in 14 men versus 7 women (p.04). The tendency towards a shorter known history of HIV infection (p.05) of females versus males may be responsible for a lower incidence of AIDS among women (p.02). The use of antiretroviral treatment was matched by time and selected regimens, but compliance proved significantly greater in females versus males (p.0001), and women had less need of a regimen switch due to poor tolerability or refusal (73.2% versus 61.1%); the latter could be responsible for a greater mean CD4+ count (p.02), and lower mean plasma viremia (p.0001), although no difference was found when considering viral suppression rate (70.7% among women, 52.8% among men). Surveillance studies and prospective therapeutic trials are strongly warranted, in order to have a reliable assessment of HIV-infected immigrated people, to check the efficacy of preventive measures, obtain validated data about the clinical, virologic, and immunological evolution and outcome of HIV infection undergoing HAART, and to evaluate the frequency and role of eventual untoward effects of pharmacologic treatment.

Adult↗

Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients.

Highly active antiretroviral therapy (HAART) has had a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with clinical and metabolic complications. Fat redistribution or lipodystrophy, hypertriglyceridaemia, hypercholesterolaemia, insulin resistance and diabetes mellitus have been extensively reported in subjects treated with protease inhibitor (PI)-based antiretroviral regimens. In particular, dyslipidaemia occurs in up to 70-80% of HIV-infected individuals receiving HAART and can be associated with all the available PIs, although hypertriglyceridaemia appears to be more frequent in patients treated with ritonavir, ritonavir-saquinavir, or ritonavir-lopinavir. The potential long-term consequences of HAART-associated hyperlipidaemia are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIV-positive persons receiving PIs. Dietary changes, regular aerobic exercise and switching to a PI-sparing regimen may act favourably on dyslipidaemia. Lipid-lowering therapy is often required with statins or fibrates. The choice of hypolipidaemic drugs should take into account potential pharmacological interactions with antiretroviral agents.

Antiretroviral Therapy, Highly Active↗

Statins and fibrates for the treatment of hyperlipidaemia in HIV-infected patients receiving HAART.

OBJECTIVES: The aim of our work is to evaluate the role of statins and fibrates in the management of hyperlipidaemia in HIV-infected patients receiving highly active antiretroviral therapy. DESIGN: Open-label, randomized, prospective study of the efficacy and safety of bezafibrate, gemfibrozil, fenofibrate, pravastatin and fluvastatin as pharmacologic treatment for protease inhibitor-related dyslipidaemia. METHODS: Plasma lipid levels of 656 HIV-infected patients who referred to our tertiary care centre and were on protease inhibitor-based antiretroviral therapy for at least 12 months have been evaluated. All patients had HIV viral load < 50 copies/ml and presented with hypertriglyceridaemia of at least 6 months duration that was unresponsive to a hypolipidaemic diet; all have been treated with bezafibrate, gemfibrozil, fenofibrate, pravastatin, or fluvastatin for 12 months. RESULTS: Of the 656 patients observed 113 (17.2%) received pharmacological therapy, while seven patients were excluded from evaluation due to early drop-out. Of the 106 evaluable subjects, bezafibrate was used in 25 cases, gemfibrozil in 22, fenofibrate in 22, pravastatin in 19, and fluvastatin in 18. At the close of 1-year follow-up, fibrates led to a reduction of 40.7% and 21.9% versus baseline triglyceridaemia and cholesterolaemia, respectively (P < 0.001), and statins led to a reduction of 34.8% and 25.2% versus baseline triglyceride and total cholesterol levels, respectively (P < 0.001), without significant differences according to each different administered hypolipidaemic drug. CONCLUSIONS: All administered statins and fibrates revealed a similar, significant efficacy in the treatment of diet-resistant hyperlipidaemia, and showed a favourable tolerability profile.

Adult↗

[Osteonecrosis in HIV-infected patients and its correlation with highly active antiretroviral therapy (HAART)].

INTRODUCTION: The incidence of osteonecrosis has increased in HIV-infected patients over the last few years, and has been considered as a side effect of highly active antiretroviral therapy (HAART), possibly related to drug-induced hyperlipidemia. We report seven cases. OBSERVATIONS: Seven HIV-infected persons, 6 males and one female, aged 29 to 49 years, and with advanced immunodeficiency (lymphocyte CD4 count<250 cells/mm3 in all the cases). Osteonecrosis generally involved the head of the femoral, clinically presented pain and difficulty walking, and was diagnosed by magnetic resonance imaging or skeletal scintigraphy. COMMENTS: Among these 7 patients with osteonecrosis, only 4 received antiretroviral therapy at the time of the diagnosis, one presented moderate hypertriglyceridemia, and 3 had positivity for the anti-phospholipid antibodies. Hence, HAART, dyslipidemia, and auto-immunity may enhance, but are not necessarily elements in the onset of HIV-associated avascular bone necrosis.

Acquired Immunodeficiency Syndrome↗

Incidence of hyperlipidaemia in a cohort of 212 HIV-infected patients receiving a protease inhibitor-based antiretroviral therapy.

Two hundred and twelve HIV-positive patients who started a new protease inhibitor (PI)-based antiretroviral regimen between January 1998 and December 2000 in our tertiary care centre were prospectively followed-up during a 12-month study period, in order to assess the incidence of hyperlipidaemia and related clinical adverse events. At the end of 1-year follow-up, PI-containing antiretroviral treatment led to a statistically significant increase in serum triglyceride levels (P<0.005) and total and LDL-cholesterol levels (P<0.05). The overall incidence of hypertriglyceridaemia and hypercholesterolaemia was 38.2 and 25%, respectively. The incidence of increased serum triglyceride levels was significantly higher in patients treated with ritonavir (66.6%) or lopinavir/ritonavir (60.7%), compared with other PIs (P<0.04). Clinical adverse events possibly related to the hyperlipidaemia (such as cardiovascular diseases or acute pancreatitis) were not observed during the entire 12 months study period. In conformity with other previously published studies, the very high incidence of hyperlipidaemia during a PI-based therapy recognised in our work raises a big concern about its potential clinico-pathological consequences and the most convenient pharmacological management of these metabolic imbalances.

Adult↗

AIDS-associated Cryptococcus infection before and after the highly active antiretroviral therapy era: emerging management problems.

The frequency, the microbiology and clinical features of AIDS-related primary episodes and relapses of cryptococcosis, before and after the introduction of highly active antiretroviral therapy (HAART), were compared. The study covered 58 cases diagnosed before the introduction of HAART, and eight episodes since 1997. Because of negative cultures, we sought a sensitive laboratory assay such as detection of polysaccharide antigen. Despite later diagnosis, there was reduced disease mortality. Clinical suspicion for HIV-associated cryptococcosis should be maintained in immunocompromised subjects. The introduction of HAART has led to significant clinical and laboratory changes of HIV-related cryptococcosis.

AIDS-Related Opportunistic Infections↗

Hyperlipidaemia in patients with HIV-1 infection receiving highly active antiretroviral therapy: epidemiology, pathogenesis, clinical course and management.

A wide range of abnormalities of lipid metabolism have been recently described in HIV-infected patients receiving a protease inhibitor (PI)-based highly active antiretroviral therapy, including hypertriglyceridaemia and hypercholesterolaemia. The increase of plasma lipid concentrations may involve up to 70-80% of HIV-positive subjects treated with a PI-containing regimen and are frequently (but not always) associated with the fat redistribution or the lipodystrophy syndrome. Multiple pathogenetic mechanisms by which antiretroviral agents lead to dyslipidaemia have been hypothesized, but they are still controversial. The potential clinicopathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations report an increased risk of premature coronary artery diseases in young HIV-positive individuals receiving PIs, besides peripheral atherosclerosis and acute pancreatitis. A limited-to-significant improvement of increased triglyceride and cholesterol plasma levels was described in patients who replaced PIs with nevirapine, efavirenz or abacavir, but the risks of long-term toxicity and virological relapse of this treatment switching are not completely defined. A hypolipidaemic diet and regular physical exercise may act favorably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or persists for a long time. The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance. Statins are considered the first-line therapy for the PI-related hypercholesterolaemia, while fibrates are the cornerstone of drug therapy when predominant hypertriglyceridaemia is of concern.

Antiretroviral Therapy, Highly Active↗

Role of Mycobacterium xenopi disease in patients with HIV infection at the time of highly active antiretroviral therapy (HAART). Comparison with the pre-Haart period.

BACKGROUND AND SETTING: A reliable and timely clinical, radiological, and bacteriological diagnosis, and an optimal treatment of non-tubercular mycobacteriosis (including Mycobacterium xenopi disease), remain an unanswered challenge for clinicians facing immunocompromised patients, including those with HIV infection. OBJECTIVE: The aim of our survey is to report the frequency, and the epidemiological, immunological, microbiological, clinical, and therapeutic features of all confirmed HIV-associated M. xenopi disease observed from 1993-2002, with special attention paid to eventual differences that emerged after the introduction of potent antiretroviral therapy (highly active antiretroviral therapy, HAART), on the basis of an international literature update. DESIGN AND RESULTS: Our series of 17 consecutive confirmed M. xenopi infections retrieved in 14 out of 3000 patients followed for HIV disease complications raises a broad series of clinical, diagnostic, therapeutic, and prophylactic concerns. The great majority of M. xenopi disease involved the lower respiratory tract, but atypical features including cavitation and prominent exudative features became apparent in patients successfully treated with HAART, pointing out the possible role of the so-called immune reconstitution syndrome in these episodes. CONCLUSIONS: Diagnostic problems represented by late or missed identification due to slow culture and frequently concomitant opportunistic disorders, join therapeutic difficulties due to the unpredictable in vitro antimicrobial susceptibility profile of these organisms, selection of treatment and chemoprophylaxis according with clinical-radiological and microbiological suspicion, and concomitantly administered medications.

AIDS-Related Opportunistic Infections↗

Hodgkin's disease in the setting of human immunodeficiency virus infection.

The incidence of Hodgkin's disease appears to progressively increase in human immunodeficiency virus (HIV)-infected patients, with the relative risk of developing this malignancy rising from the early phase to the advanced stage of HIV disease. Clinical and pathological features of Hodgkin's lymphoma in HIV-positive subjects differ from those of the general population, showing a higher frequency of unfavourable histological subtypes, advanced stage with frequent extranodal involvement at initial diagnosis, and a poor therapeutic outcome. The optimal therapeutic strategy is still controversial, and median overall survival is short, ranging from 12 to 18 months. In this report cases of Hodgkin's disease are described among over 1,000 HIV-infected patients referring to a tertiary care centre during a 6 y study period.

Adult↗

Prospective comparison of first-line nelfinavir therapy versus nelfinavir introduction in rescue antiretroviral regimens.

In order to establish the role of the protease inhibitor nelfinavir in current clinical practice, a prospective 18-month open-label comparison of efficacy and tolerability of nelfinavir was performed among HIV-infected patients who either incorporated nelfinavir in their first-line highly active antiretroviral therapy (HAART) regimen (group A, 57 patients), or who added nelfinavir to a rescue antiretroviral regimen (following at least two attempts with protease inhibitor-based HAART) (group B, 67 patients). All evaluable data were analyzed according to the prior and concurrent antiretroviral therapy, including genotypic resistance assays for patients undergoing salvage therapy. A significantly better virologic outcome (as expressed by a > 2 log(10) drop of plasma viremia versus baseline or attainment of undetectable levels), was shown among patients belonging to group A versus group B, where a number of genotypic mutations possibly elicited by previous anti-HIV treatment strongly impaired a potent and sustained nelfinavir activity. On the whole, the immunologic response (as expressed by the mean CD4(+) lymphocyte count versus baseline), substantially paralleled the virologic one in all analyzed subgroups, but a tendency toward a maintained immunologic competence was also observed in the majority of patients experiencing virologic failure. Nelfinavir introduction was sufficiently safe, because a limited percentage of patients suffered from mild-to-moderate, novel, or continuing adverse events, which proved significantly more frequent in the salvage group but did not affect adherence to HAART.

Antiretroviral Therapy, Highly Active↗

Ampicillin, gentamicin and teicoplanin as antimicrobial therapy for recurrent Streptococcus agalactiae and Enterococcus faecalis endocarditis in an intravenous drug abuser with HIV infection.

Infective endocarditis associated with human immunodeficiency virus (HIV) infection occurs almost exclusively in intravenous (i.v.) drug users and usually involves the tricuspid valve, with an increased mortality rate among patients with a severe degree of immunosuppression. The first reported case of recurrent tricuspid endocarditis sustained by Streptococcus agalactiae and Enterococcus faecalis in an i.v. drug addict during HIV infection is presented. Antimicrobial therapy with i.v. ampicillin, gentamicin and teicoplanin led to complete clinical and echocardiographical recovery.

Adult↗

Systemic and discoid lupus erythematosus in HIV-infected patients treated with highly active antiretroviral therapy.

Although HIV infection is often associated with several rheumatic diseases, the coexistence of this retroviral infection and systemic lupus erythematosus (SLE) is extremely uncommon. Generally, HIV-related immunosuppression improves SLE symptoms, and antiretroviral therapy may lead to an autoimmune disease flare subsequent to the increase of circulating CD4+ cell number. Two HIV-infected female patients with SLE and discoid lupus erythematosus (DLE) diagnosed a few months after the highly active antiretroviral therapy initiation, are described. To our knowledge, this is the second case of DLE and the twenty-seventh case of SLE reported to date in association with HIV infection.

Adult↗