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Objectives: Statins are lipid-lowering drugs that exhibit anti-Inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. Design: To assess the anti-inflamatory effects of statins in HIV-infected patients, because very limited data are available today. Methods: Longitudinal, observational study of HIV-infected adult patients naive to antiretroviral therapy who started tenofovir/emtricitabine/efavirenz and were followed-up for 48 weeks. Patients with baseline normal cholesterol level and taking only antiretroviral drugs (group A) were compared to those with baseline hypercholesterolemia who received rosuvastatin (10 mg daily) in association with antiretroviral treatment (group B). The primary observation was change in serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], interleukin-8 [IL-8]) and tumor necrosis factor-α [TNF- α]) in both groups, whereas secondary observations include variations in CD4 lymphocyte count, HIV viral load, and occurrence of adverse events. Results: Eighty-six patients were enrolled into the study: 46 in group A and 40 in group B. After 48 weeks, patients treated with antiretroviral therapy plus rosuvastatin had significantly greater decreases in serum concentrations of all Inflammatory markers than those taking antiretroviral therapy only. Changes in mean levels of hsCRP and TNF-α were -35.1% and -22.4% in group B and -8.2% and 5.4% in group A, respectively (P < .001, for both parameters). No significant differences in immunovirological parameters and safety profile were reported across the compared groups. Conclusions: Our findings suggest that tenofovir/emtricitabine/efavirenz plus rosuvastatin has a greater antiInflammatory effect than antiretroviral drugs only. [ABSTRACT FROM AUTHOR]

Background: Statins are lipid-lowering drugs that exhibit anti-inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. Objective: Because very limited data are available today, our objective was to assess the lipid-lowering effects of statins and their capacity to decrease selected soluble markers of inflammation in HIV-infected patients. Methods: Retrospective cohort study of HIV-infected adult patients with hypercholesterolemia who were receiving a stable antiretroviral regimen including a ritonavir-boosted protease inhibitor and who started a lipid-lowering therapy with rosuvastatin (10 mg daily), atorvastatin (10 mg daily), or pravastatin (40 mg daily) and were followed-up for at least 12 months. One hundred and fifty-one patients were enrolled in the study: 51 in the rosuvastatin group, 47 in the atorvastatin group, and 53 in the pravastatin group. The primary observation was change in plasma lipid levels and serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF- α]), while secondary observations include immunovirological parameters and safety profile of statins. Results: One year after starting the statin therapy, patients treated with rosuvastatin had significantly greater decreases in total cholesterol and LDL cholesterol than subjects on atorvastatin or pravastatin. All statins led to a similar, significant reduction in serum levels of hsCRP and TNF-α, without correlation between biomarkers and lipid values, and toxicity rates were similar for all 3 statins. Conclusion: Our findings suggest that rosuvastatin has a significantly greater lipid-lowering effect than atorvastatin or pravastatin, but all 3 statins exert a similar effect in lowering markers of inflammation as hsCRP and TNF-α. [ABSTRACT FROM AUTHOR]

Summary: The use of new potent protease inhibitor-based antiretroviral therapies in patients with human immunodeficiency virus (HIV) infection has been increasingly associated with cardiovascular risk factors, including hyperlipidaemia, fat redistribution syndrome, insulin resistance, and diabetes mellitus. The introduction of highly active antiretroviral therapy (HAART) in clinical practice has remarkably changed the natural history of HIV disease, leading to a notable extension of life expectancy, and prolonged lipid and glucose metabolism abnormalities are expected to lead to significant effects on the long-term prognosis and outcome of HIV-infected patients. Prediction modeling, surrogate markers and hard cardiovascular endpoints suggest an increased incidence of cardiovascular diseases in HIV-infected subjects receiving HAART, even though the absolute risk of cardiovascular complications remains still low, and must be balanced against the evident virological, immunological, and clinical benefits descending from combination antiretroviral therapy. Nevertheless, the assessment of cardiovascular risk should be performed on regular basis in HIV-positive individuals, especially after initiation or change of antiretroviral treatment. Appropriate lifestyle measures (including smoking cessation, dietary changes, and aerobic physical activity) are critical points, and switching HAART may be considered, although maintaining viremic control should be the main goal of therapy. Pharmacological treatment of dyslipidaemia (usually with statins and fibrates), and hyperglycaemia (with insulin-sensitizing agents and thiazolidinediones), becomes suitable when lifestyle modifications and switching therapy are ineffective or not applicable. [Copyright &y& Elsevier]

One thousand and eighty-one evaluable HIV-infected patients were assessed for pancreatic abnormalities in a prospective case–control study including the whole follow-up period of each patient (minimum 12 months). The 435 patients (40.2%), who experienced at least one episode of confirmed pancreatic laboratory abnormality had a longer duration of seropositivity, exposure to protease inhibitors, a more frequent immunodeficiency, AIDS, chronic liver and/or biliary disease and hypertriglyceridaemia, while no relation was found with antiretroviral administration, and the duration of type of nucleoside analogues, when compared with the 646 controls. High and prolonged laboratory alterations eventually associated with signs of organ involvement occurred in 166 cases (38.2%), and were related to the administration of didanosine, stavudine, lamivudine, pentamidine, cotrimoxazole or antitubercular/antimycobacterial therapy, cytotoxic chemotherapy, illicit substance or alcohol abuse, opportunistic infections, chronic liver and/or biliary disease, a protease inhibitor-based highly active antiretroviral therapy (HAART) and hypertriglyceridaemia (usually associated with HAART administration). No difference was noticed between the 46 patients with clinical and/or imaging evidence of pancreatic involvement and the 120 asymptomatic subjects. Although recurrences of enzyme alterations involved 69.6% of patients, only in 30.1% of cases did a change of the underlying antiretroviral or antimicrobial therapy become necessary. An acute, uncomplicated pancreatitis occurred in nine of the 46 symptomatic subjects (19.6%). A two to four week gabexate and/or octreotide administration (performed in 79 cases of 166, 47.6%), achieved a significant laboratory, clinical and imaging cure or improvement in 82.3% of cases, with a better success rate of combined (gabexate mesilate plus octreotide) vs. single (gabexate mesilate or ocreotide) therapy. Reduced disease recurrences and a better tolerability of antiretroviral regimens, were also noticed. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the temporal trend of deaths in a cohort of intravenous (IV) drug users (IVDU) followed in a city in Northern Italy (Bologna), and to assess its relationship with HIV infection and AIDS, and availability of potent antiretroviral therapy. Methods: A total of 1214 IVDUs (mainly heroin addicts). 916 males and 298 females, attending an outpatient service for treatment and prevention of substance abuse between 1977 and November 1996, were enrolled into our observational cohort. Their vital status was ascertained up to December 31, 2002. Results: The large majority of enrolled subjects were born in the Bologna metropolitan area and surroundings; no extra-European immigrants were pres present. During the observation period. 271 IVDUs (22.3%) died, 211 males (23.0%), and 60 females (20.1 %). No death was recorded before 1984. Main death causes were as follows: AIDS (52.8% of deaths), heroin overdose (22.1%), street accidents (7.4%), decompensated liver cirrhosis (6.3%), and suicide (2.9%). The highest absolute number of deaths was observed between years 1991 and 1996. Crude mortality rate caused by AIDS was 10.0 per 1000 for males and 13.2 per 1000 for females; the rate of death due to other causes proved 11.1/1000 among males and 5.2/1000 among females. Conclusion: In most recent years, a sharp decrease in the number of AIDS related deaths, attributable to the increased use of potent antiretroviral regimens, was recorded among IVDUs, although overall mortality rate remained appreciable. [ABSTRACT FROM AUTHOR]

Compares the effectiveness and tolerability of the nonnucleoside reverse transcriptase inhibitors, afavirenz versus nevirapine in all possible indications of current clinical practice. Baseline assessment; Follow-up of efficacy parameters; Tolerability evaluation; Efficacy parameters.

An extraordinarily rare case report of mixed fat redistribution syndrome associated with osteopenia but not with relevant metabolic abnormalities is documented in a prepubertal child with congenital HIV infection treated with antiretroviral therapy since the age of six months, up to the present age of 12 years and two months. The possible relationship with prior and present antiretroviral treatment, and with the most recent literature evidences published in both adults and children with HIV disease are discussed, in order to focus these emerging adverse effects of long-term antiretroviral therapy in the paediatric population, and stimulate further investigation in this field. [ABSTRACT FROM AUTHOR]

An evaluation was made of the frequency of outcomes, the features, and one-year outcomes of the substitution, carried out because of failure or toxicity, of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART). Nine hundred and seventy-two HIV-infected patients were prospectively followed up since 1996, with the condition that they had a minimum 80% adherence to prescribed regimens. Four hundred and fifty-two changes occurred in 397 of the 876 evaluable patients (45.3%). Virological and/or immunological failure was of concern in 245 cases (54.2%). Interest in saquinavir had the greatest incidence and earliest occurrence (although the subsequent switch had a significantly better outcome than that of patients failing with other PIs); nelfinavir benefited from a shorter time to change and a worse long-term outcome (probably attributable to its predominant use in indinavir- and ritonavir-experienced patients); while indinavir showed the lowest overall frequency of substitution. Intolerance occurred in the remaining 207 cases (45.8%); with saquinavir being better tolerated than other PIs. A favourable outcome was obtained more frequently when poor tolerability was of concern, compared with therapeutic failure (P <0.008), while no significant differences were found according to prior antiretroviral experience and the subsequently selected HAART regimen. The overall one-year outcome per single substituted compound proved significantly better for patients who stopped using saquinavir and ritonavir, by contrast with those who stopped using indinavir and nelfinavir (P < 0.0008). A significantly shorter mean time to substitution was recognized for nelfinavir and saquinavir than with ritonavir and indinavir (P < 0.0001). When analysing the subset of patients experiencing HAART failure, a highly significant reverse relationship was demonstrated between mean time to failure, and rate of subsequent response to a modified antiretroviral regimen (P < 0.0001). When considering the different patterns of efficacy, durability, resistance induction, expected adherence, and safety of each antiretroviral drug, initial and subsequent therapeutic choices should be carefully balanced against expected benefits and risks. [ABSTRACT FROM AUTHOR]

A possible association between carpal tunnel syndrome and HIV infection has been suggested only once until now. Two patients with HIV infection are described who presented confirmed carpal tunnel syndrome while on prolonged protease inhibitor-containing highly active antiretroviral therapy (HAART). Their disease course and long-term outcome after medical and/or surgical interventions is presented and discussed according to available evidence from the literature. In our patients, carpal tunnel syndrome occurred in apparent absence of all presumed risk factors of this disease and metabolic abnormalities potentially related to HIV protease inhibitor administration. [ABSTRACT FROM AUTHOR]

A 16-year-old girl with vertical HIV disease treated since birth suffered from six different AIDS-defining disorders until now. Even during the highly active antiretroviral therapy, multiple AIDS-related opportunistic infections may complicate the course of long-term congenital HIV disease, showing a strict relationship with immunological deterioration, which occurs shortly after virologic failure, due to an extensive genotypic resistance to all available antiretroviral compounds. [ABSTRACT FROM AUTHOR]