Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy.

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150 mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17 mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: randomised controlled trial.

OBJECTIVE: Impaired endothelial function was demonstrated in HIV-infected persons on protease inhibitor (PI)-containing antiretroviral therapy, probably due to altered lipid metabolism. Atazanavir is a PI causing less atherogenic lipoprotein changes. This study determined whether endothelial function improves after switching from other PI to atazanavir. DESIGN: Randomised, observer-blind, treatment-controlled trial. SETTING: Three university-based outpatient clinics. PATIENTS: 39 HIV-infected persons with suppressed viral replication on PI-containing regimens and fasting low-density lipoprotein (LDL)-cholesterol greater than 3 mmol/l. INTERVENTION: Patients were randomly assigned to continue the current PI or change to unboosted atazanavir. MAIN OUTCOME MEASURES: Endpoints at week 24 were endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery, lipid profiles and serum inflammation and oxidative stress parameters. RESULTS: Baseline characteristics and mean FMD values of the two treatment groups were comparable (3.9% (SD 1.8) on atazanavir versus 4.0% (SD 1.5) in controls). After 24 weeks' treatment, FMD decreased to 3.3% (SD 1.4) and 3.4% (SD 1.7), respectively (all p = ns). Total cholesterol improved in both groups (p<0.0001 and p = 0.01, respectively) but changes were more pronounced on atazanavir (p = 0.05, changes between groups). High-density lipoprotein and triglyceride levels improved on atazanavir (p = 0.03 and p = 0.003, respectively) but not in controls. Serum inflammatory and oxidative stress parameters did not change; oxidised LDL improved significantly in the atazanavir group. CONCLUSIONS: The switch from another PI to atazanavir in treatment-experienced patients did not result in improvement of endothelial function despite significantly improved serum lipids. Atherogenic lipid profiles and direct effects of antiretroviral drugs on the endothelium may affect vascular function. TRIAL REGISTRATION NUMBER: NCT00447070.

Lipodystrophy and weight changes: data from the Swiss HIV Cohort Study, 2000-2006.

BACKGROUND AND OBJECTIVES: Combination antiretroviral therapy (cART) is changing, and this may affect the type and occurrence of side effects. We examined the frequency of lipodystrophy (LD) and weight changes in relation to the use of specific drugs in the Swiss HIV Cohort Study (SHCS). METHODS: In the SHCS, patients are followed twice a year and scored by the treating physician as having 'fat accumulation', 'fat loss', or neither. Treatments, and reasons for change thereof, are recorded. Our study sample included all patients treated with cART between 2003 and 2006 and, in addition, all patients who started cART between 2000 and 2003. RESULTS: From 2003 to 2006, the percentage of patients taking stavudine, didanosine and nelfinavir decreased, the percentage taking lopinavir, nevirapine and efavirenz remained stable, and the percentage taking atazanavir and tenofovir increased by 18.7 and 22.2%, respectively. In life-table Kaplan-Meier analysis, patients starting cART in 2003-2006 were less likely to develop LD than those starting cART from 2000 to 2002 (P<0.02). LD was quoted as the reason for treatment change or discontinuation for 4% of patients on cART in 2003, and for 1% of patients treated in 2006 (P for trend <0.001). In univariate and multivariate regression analysis, patients with a weight gain of >or=5 kg were more likely to take lopinavir or atazanavir than patients without such a weight gain [odds ratio (OR) 2, 95% confidence interval (CI) 1.3-2.9, and OR 1.7, 95% CI 1.3-2.1, respectively]. CONCLUSIONS: LD has become less frequent in the SHCS from 2000 to 2006. A weight gain of more than 5 kg was associated with the use of atazanavir and lopinavir.

Disseminated tuberculosis following total knee arthroplasty in an HIV patient.

Skeletal tuberculosis is now uncommon in developed countries. In immunocompromised patients--particularly in the HIV-infected--who present with subacute or chronic joint pain refractory to conventional treatment, osteoarticular tuberculosis should still be included in the differential diagnosis. We report on a lethal case of disseminated tuberculosis in an HIV-infected subject. Dissemination may have resulted from the implantation of an articular prosthesis in a knee joint with unsuspected osteoarticular tuberculosis. The diagnosis was established months later when the patient presented with far-advanced tuberculous meningitis, miliary tuberculosis of the lungs, femoral osteomyelitis and extended cold abscesses along the femoral shaft. Failure to respond to a conventional four-drug regimen is explained by the resistance pattern of his multi-drug resistant strain of Mycobacterium tuberculosis, which was only reported after the patient's death. This case illustrates the diagnostic challenges of osteoarticular tuberculosis and the consequences of a diagnostic delay in an HIV-infected individual.

[Acute infectious emergencies in adults in medical practice]. / Der akute infektiologische Notfall beim Erwachsenen in der Praxis.

Infectious diseases belong to the most frequent reasons to seek emergency care. Life-threatening infectious emergencies, which require rapid diagnosis and hospitalisation, are, however, rare. Leading signs and symptoms are high fever combined with rapidly deteriorating general conditions, hypotonia, tachycardia, tachypnea, dyspnea, confusion, headache, or petechia or information about asplenia, immunosuppression or recent travel to the tropics. Life threatening situations, such as suspicion of invasive meningococcal infection or bacterial infection in an asplenic patient, septic-toxic shock, and acute bacterial meningitis with delayed hospitalisation require rapid start of empiric antibiotic therapy in the outpatient practice. In addition, acute infectious emergencies comprise situation for which post exposure prophylaxis is indicated.

[Antiretroviral therapy and pregnancy]. / Antiretrovirale Medikamente und Schwangerschaft.

Whereas the perinatal transmission rate with untreated HIV positive women is around 30%, the results of Pediatric AIDS Clinical Trials Group in 1994 showed a reduction by nearly 70% with Zidovudin chemoprophylaxis. The transmission rate can even be reduced to under 2%, if a cesarean section before onset of labour and before premature rupture of membranes is done in addition. An individualized, optimal antiretroviral combination therapy, ideally introduced in the second trimenon (in special cases even already in the first trimenon), is of great importance. As a further strategy of prevention of perinatal transmission, intravenous Zidovudin chemoprophylaxis should be given in addition to the mother during labour and to the newborn during the first six weeks of life. Besides very few exceptions, long-term data after intrauterine administration of antiretroviral therapy do not show any teratogen or other long term consequences to date. The situation in developing countries is very critical with still high transmission rates because of the lack of antiretroviral therapy due to logistical reasons and costs and the need of breastfeeding. For these reasons, more and more feasible short protocols are developed with at least fifty percent reduction of neonatal transmission rates.

[Septic endarteritis after angiography]. / Septische Endarteriitis nach Angiographie.

Infectious complications after angiography are rare. We treated a 72-year-old man who developed staphylococcus aureus endarteritis after angiography resulting in delayed rupture of the common iliac artery. Diagnostic problems, type of bacteria involved and therapeutic implications are discussed.

Intensive care unit admission in patients with haematological disease: incidence, outcome and prognostic factors.

OBJECTIVES: To examine incidence and outcome of intensive care unit (ICU) admission in patients with haematological malignancy and analyse prognostic factors associated with outcome. DESIGN: Retrospective cohort study in an intensive care unit of a tertiary referral center. PATIENTS: 78 patients with severe haematological malignancy were admitted 97 times between 1990-97 to the medical ICU for septic shock (18), respiratory failure (30), postoperative monitoring (19), cardiovascular (10) and central nervous complications (8) or for other reasons (12). Median age was 43 (4-73) years, average duration of ICU stay was 4 (1-43) days. Forty-two patients required mechanical ventilation, 46 vasopressors and 8 haemodialysis. RESULTS: Rates of ICU admission differed by treatment of the underlying disease. There were 18, 10 and 27 ICU admissions per 100 treatments in patients undergoing chemotherapy for acute leukaemia, autologous and allogeneic stem cell transplantation (p <0.005) respectively. Thirty-two of 78 patients died within 60 days of ICU admission. Organ failure, i.e. cardiovascular failure requiring vasopressors, respiratory failure requiring mechanical ventilation and renal failure, requiring haemodialysis, was most significantly associated with outcome. Mortality by day 60 after admission was 16%, 36%, 64%, and 83% (p <0.0002) for patients without organ failure, and for patients with 1, 2 or 3 failing organs. In a multivariate logistical regression model, only the organ failure score (p <0.0005) and evidence of liver damage, defined as ASAT or ALAT >100 IU/ L (p <0.007), but not age, sex, primary disease and treatment of the underlying disease predicted outcome. CONCLUSION: Multi-organ failure and evidence of liver damage but no other patient, disease, or treatment related factor predict outcome in patients with haematological disease admitted to the ICU.

[Liver cell carcinoma as a late complication of Alagille syndrome (arterio-hepatic dysplasia)]. / Leberzellkarzinom als Spätkomplikation des Alagille-Syndroms (arterio-hepatische Dysplasie).

The Alagille syndrome which is also known as arterio-hepatic dysplasia is an autosomal dominant inherited disorder. In several cases cytogenetic studies revealed an interstitial deletion of the short arm of chromosome 20. The hypoplasia or paucity of the interlobular bile ducts causes a chronic intrahepatic cholestasis. The association with facial dysmorphia, embryotoxon posterior, pulmonary stenosis and vertebral deformities are required for the diagnosis of the complete Alagille syndrome. The occurrence of hepatocellular carcinoma as a late complication of the Alagille syndrome was recognized only 11 years after the first publication by Alagille et al. So far 15 cases complicated by hepatocellular carcinoma have been reported. There is one family where all four siblings suffered from hepatocellular carcinoma. Our own case concerns a 31 year old man who died of hepatocellular carcinoma. The postmortem study of his medical history reaching back to childhood allowed the diagnosis of an unrecognized Alagille syndrome.

[Prevention of cerebrovascular insults]. / Prävention des zerebrovaskulären Insults (CVI).

Cerebrovascular infarction is the third leading cause of mortality following coronary heart disease and malignancies. WHO studies show that more than half of patients admitted for cerebrovascular infarction were not treated for hypertension. The risk factors for coronary heart disease and cerebrovascular infarction are not identical. Patients with systolic and diastolic hypertension, atrial fibrillation, stenosis of the carotid artery, and smoking, have a significantly elevated risk for cerebrovascular accidents. Hypercholesterolemia and diabetes are less important risk factors. Risk factors amendable by adequate nutritional intake are low supply of carotene and vitamin C. Homocysteineemia appears to be a risk factor that may be influenced by appropriate nutrition. Antihypertensive therapy is the most important primary and secondary preventive measure. No smoking and adequate dietary intake are also important. Primary prevention with low dose salicylic acid (ASA) is recommended in the presence of additional cardiovascular risk factors. The benefit of low dose anticoagulant therapy in atrial fibrillation without symptoms is not fully established. In subjects with atrial fibrillation with cerebrovascular events anticoagulants are superior to ASA. Surgical treatment of significant stenosis of the carotid artery is indicated. In secondary prevention of thromboembolic events, low dose ASA is recommended. A valuable alternative in case of side effects is available in ticlopidine.