Long-term use of rosuvastatin: a critical risk benefit appraisal and comparison with other antihyperlipidemics

Rosuvastatin represents the latest inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase introduced in clinical practice for the treatment of hypercholesterolemia. In comparative trials, across dose ranges this statin reduced low-density lipoprotein (LDL) cholesterol and total cholesterol significantly more than atorvastatin, simvastatin, and pravastatin, and triglycerides significantly more than simvastatin and pravastatin. In healthy subjects with normal LDL cholesterol and elevated C-reactive protein, rosuvastatin treatment significantly decreased the incidence of cardiovascular events. Its chemical and pharmacokinetic properties (with a low lipophilicity and poor capacity to inhibit cytochrome P450 enzymes) suggest a very limited penetration in extrahepatic tissues with a lower risk of muscle toxicity and unlike metabolically mediated drug–drug interactions. This article reviews the most recent data on the pharmacologic and clinical properties of rosuvastatin, in order to enable the correct use of this statin for the treatment of hypercholesterolemia

Use of rosuvastatin to treat protease inhibitor-associated hypercholesterolaemia in a HIV-infected patient at high risk of cardiovascular diseases

Rosuvastatin represents one of the latest inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase introduced in clinical practice for the treatment of hypercholesterolaemia. In comparative trials, across dose ranges this statin reduced low-density lipoprotein (LDL) cholesterol and total cholesterol significantly more than atorvastatin, simvastatin, and pravastatin, and triglycerides significantly more than simvastatin and pravastatin. In healthy subjects with normal LDL cholesterol and elevated C-reactive protein, rosuvastatin treatment produced a significant decrease in the incidence of cardiovascular events.Its chemical and pharmacokinetic properties suggest a very limited penetration in extrahepatic tissues with a lower risk of muscle toxicity and metabolically mediated drug-drug interactions, suggesting a low risk of pharmacokinetic interactions with antiretroviral drugs in patients with HIV infection. We describe a case of protease inhibitor-associated hypercholesterolaemia in a male HIV-infected patient with high cardiovascular risk. Treatment with rosuvastatin leaded to a significant reduction in total and LDL cholesterol levels, with a good tolerability profile after 15 months of follow-up

The risk of myocardial infarction during HIV infection treated with antiretroviral combinations. A review

Highly active antiretroviral therapy (HAART) has dramatically reduced morbidity and mortality associated with acquired immunodeficiency syndrome (AIDS), and human immunodeficiency virus (HIV) infection has become a chronic and manageable disease. Paralleling increased life expectancy, HIV-infected subjects may present many comorbidities, most notably cardiovascular diseases, and recent studies have identified an increased prevalence of traditional coronary risk factors in these patients. Moreover, additional investigations suggest that HIV itself may independently favour premature atherosclerosis, and antiretroviral agents also could directly or indirectly play a role in the atherosclerotic process. Dyslipidaemia, insulin resistance, inflammation, and fat redistribution are all likely to contribute to this pathogenetic pathway, and these abnormalities may be interrelated and due to either HIV infection, or the related inflammatory syndrome, or HAART-associated toxicity. Appropriate screening and assessment of cardiovascular risk and intensive strategies for prevention of cardiovascular events are suitable in HIV-infected patients, including lifestyle measures, switching antiretroviral drugs, and pharmacologic therapy of lipid and glucose metabolism alterations. This article reviews the correlation between HIV infection and myocardial infarction, and discusses the most appropriate clinical management of cardiovascular risk among HIV-positive individuals

Assessment of Kidney Safety Parameters Among Hiv-Infected Patients Starting a Tenofovir-Containing Antiretroviral Therapy

To better evaluate the renal safety profile of tenofovir, we performed a retrospective study of HIV-infected naive patients starting a first antiretroviral therapy between July 2005 and July 2008, and followed-up for 24 months. On the whole, 324 patients were enrolled: 201 tenofovir-exposed patients were compared with 123 tenofovir-unexposed subjects. In both unadjusted and adjusted analysis, tenofovir-exposed subjects had a significantly greater decline in glomerular filtration rate (GFR), and a significantly higher incidence of proximal tubular dysfunction through 24 months. Reduced glomerular and tubular functions were significantly associated with older age, diabetes, hypertension, and concomitant therapy with a HIV protease inhibitor

Severe brain co-infection with Cryptococcus neoformans and Mycobacterium tuberculosis in a young, otherwise healthy student recently immigrated from China

Summary Introduction While the incidence of pulmonary and extrapulmonary tuberculosis is growing in patients of advanced age, immunocompromised subjects, and immigrants coming in from developing countries [Keller A, Delavelle J, Howarth N, Bianchi S, Garcia J. Spinal and neurotuberculosis in an Asian immigrant. JBR-BTR 2002; 85 :136–7; Sabbatani S, Manfredi R, Legnani G. Chiodo F. Tuberculosis in a metropolitan area of northern Italy: epidemiological trends and public health concerns. Eur J Epidemiol 2004; 19 :501–3], the concomitant occurrence of cerebral cryptococcosis plus brain and respiratory tuberculosis in a young and otherwise healthy patient, without an evident cause of immunodeficiency and without an obvious exposure, is exceedingly rare [Silber E, Sonnenberg P, Koornhof HJ, Morris L, Saffer D. Dual infective pathology in patients with cryptococcal meningitis. Neurology 1998; 51 :1213–5.]. Case report An exceptionally rare case of concurrent central nervous system infection with Cryptococcus neoformans and Mycobacterium tuberculosis in a 25-year-old otherwise healthy Chinese student, who had very recently joined an Italian post-doctoral course, is described. Also described are the diagnostic and therapeutic difficulties encountered in a five-month hospitalization period, when only transient and/or negligible immune system impairments were detected. Conclusions This episode of very infrequent concurrent infections should emphasize the need to maintain an elevated clinical suspicion for opportunistic infections and tuberculosis, even in the absence of an obvious immunodeficiency and related epidemiological clues

Increasing pathomorphism of pulmonary tuberculosis: an observational study of slow clinical, microbiological and imaging response of lung tuberculosis to specific treatment. Which role for linezolid?

During recent years, a progressive emerging of tuberculosis occurred, related to the overall increased age of general population, primary and secondary (iatrogenic) immunodeficiencies, the availability of invasive procedures, surgical interventions and intensive care supports, bone marrow and solid organ transplantation, and especially the recent immigration flows of people often coming from areas endemic for tuberculosis, and living with evident social-economical disadvantages, and with a reduced access to health care facilities. Since January 2006, at our reference centre we followed 81 consecutive cases of pulmonary tuberculosis, with 65 of them which remained evaluable for the absence of extrapulmonary complications, and a continuative and effective clinical and therapeutic follow-up. The majority of episodes of evaluable pulmonary tuberculosis (49 cases out of 65: 75,4%) occurred in patients who immigrated from developing countries. In two patients multiresistant (MDR) Mycobacterium tuberculosis strains were found, while two more subjects (both immigrated from Eastern Europe) suffered from a disease due to extremely resistant (XDR) M. tuberculosis strains. Although enforcing all possible measures to increase patients' adherence to treatment (empowerment, delivery of oral drugs under direct control, use of i.v. formulation whenever possible), over 72% of evaluable patients had a very slow clinical, microbiological, and imaging ameliorement (1-6 months), with persistance of sputum and/or bronchoalveolar lavage (BAL) fluid positive for M.tuberculosis microscopy and/or culture for over 1-4 months (mean 9.2±3.2 weeks), during an apparently adequate treatment. When excluding patients suffering from XDR and MDR tuberculosis, in four subjects we observed that off-label linezolid adjunct together with at least three drugs with residual activity against tuberculosis, led to a significantly more rapid clinical-radiological improvement and negative microbiological search, with consequent possibility to led to a protected discharge, supported by a sequential, oral therapy. Linezolid was also successfully employed in all the four patients with XDR or MDR pulmonary tuberculosis: among these patients, a definitive or temporarily negativization of respiratory secretions, and consequent discharge, was achieved only after linezolid adjunct. Notwithstanding the maintained microbiological susceptibility of M. tuberculosis strains responsible of the great majority of cases of pulmonary tuberculosis to first-line drugs, an unexpected tendency of patients to have a persistingly positive sputum and/or BAL, and to experience prolonged hospitalization for cure and isolation, has been recognized in the last years. No particularly suggestive radiological imaging seems predictive of a so prolonged course, so that we presently lack of clinical and imaging elements which may be predictive of this slow treatment response. The same is for demographic and epidemiological issues, eventual underlying diseases, and clinical presentation, so that a major problem for health care providers is to distinguish upon admission patients who will be prone to have slow therapeutic response and a related prolonged hospitalization. The novel oxazolidinone linezolid is characterized by an affordable in vitro activity against M. tuberculosis, and an extremely elevated intracellular concentration in respiratory tissues. Worldwide, increasing microbiological, pharmacological, and clinical evidences may recommend the use as linezolid adjunct as an off-label salvage treatment of pulmonary tuberculosis refractory to treatment, although not necessarily determined by resistant (MDR-XDR) M. tuberculosis strains. Randomized clinical trials including initially patients with ascertained chemioresistant tuberculosis, are strongly warranted

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs), represents the key point for a debate around the increasing frequency of “polypharmacy” in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs), represents the key point for a debate around the increasing frequency of "polypharmacy" in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS