Prevention of atherosclerosis in patients living with HIV

Ferruccio De Lorenzo1, Marta Boffito1, Sophie Collot-Teixeira2, Brian Gazzard1, John L McGregor2,3, Kevin Shotliff2, Han Xiao41General Medicine and Prevention of Vascular Disorders, Beta Cell Diabetes Centre and St Stephen’s AIDS Trust, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; 2Kings College London, Cardiovascular Division, London, UK; 3INSERM U970, PARC Hôpital Européen George Pompidou, Paris, France; 4Cardiology Department, Homerton University Hospital NHS, London, UKInvestigational product: Rosuvastatin (Crestor®; Astra Zeneca).Active ingredients: Rosuvastatin (5 mg).Study title: Prevention of Atherosclerosis in Patients Living with HIV.Phase of study: Phase III.Aims: Primary aim:• To assess whether rosuvastatin therapy could slow the progression of the carotid intima-media thickness (C-IMT; as measured by the change in the mean IMT of the near and far walls of the distal common carotid arteries) over 2 years in HIV-infected patients (HIV-IP).Secondary aims:• To assess whether rosuvastatin therapy could reduce highly sensitive C reactive protein (hs-CRP) inflammatory marker that is increased in HIV-IP.• To assess the effect of rosuvastatin therapy on serum lipid levels (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and apolipoproteins (APO A1, APO B and APO B/A1).• To assess the safety of rosuvastatin in HIV-IP through the evaluation of clinical laboratory analyses (liver function tests and creatine kinase) and adverse events (AEs).Study design: Two-year randomized, double-blind, placebo-controlled, parallel group study.Planned sample size: 320 HIV-IP.Summary of eligibility criteria: HIV-IP who are aged between 30 and 60 years, with a CD4 count. greater than 200 cells/mm3. Patients must be stable on combination antiretroviral therapy (cART) for at least 12 months and have a 10-year CVD risk of less than 20% (using the Framingham risk score).Number of study centers: One.Duration of treatment: Two years (5 mg rosuvastatin or placebo once daily).Dose and route of administration: Oral rosuvastatin (5 mg) once daily.The incidence of cardiovascular disease (CVD) in HIV-IP is at least three times higher than in the general population and further increases each year with combination anti-retroviral therapy (cART). The carotid atherosclerosis progression rate is 10 times higher in HIV-IP than in uninfected individuals. The aim of this study is to assess whether therapy with 5 mg rosuvastatin could:1) Slow the progression in the mean IMT of the distal common carotid arteries over two years in HIV-IP.2) Change the concentration in the inflammatory marker – hs-CRP, which is increased in HIV-IP.3) Change the concentrations of TC, LDL cholesterol, HDL cholesterol, TG, apolipoproteins (APO) B, APO A1 and APO B/A1.4) Be administered safely in the study population.Pharmacological intervention with rosuvastatin will be evaluated in a double-blind, placebo-controlled, randomized clinical trial in HIV-IP treated with cART not matching the published selection criteria for lipid-lowering therapy. For the first time, this study will investigate anti-inflammatory and anti-atherogenic effects of a pharmacological lipid-lowering agent in HIV-IP that may lead to the reduction of CVD.Keywords: rosuvastatin, atherosclerosis, cardiovascular disease, HIV, clinical trial protoco

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Bariatric surgery in individuals with human immunodeficiency virus and type 2 diabetes: a case series

Abstract Background The efficacy and safety of bariatric surgery have not been fully elucidated in patients affected with human immunodeficiency virus. Although adjustable gastric banding and sleeve gastrectomy are starting to be used in patients with human immunodeficiency virus, there are limited descriptions of the outcomes of type 2 diabetes mellitus in individuals who are human immunodeficiency virus positive and undergoing these procedures. Case presentation We have evaluated retrospectively three patients who underwent adjustable gastric banding or sleeve gastrectomy, the effect in weight reduction and glycemic control as well as its impact on human immunodeficiency virus management. Case 1 (adjustable gastric banding), a 58-year-old Caucasian male, achieved 19% total weight loss, Case 2, a 33-year-old Caucasian male (sleeve gastrectomy) lost 25%, and Case 3, a 48-year-old Caucasian female (sleeve gastrectomy), lost 14% postoperation. In terms of type 2 diabetes mellitus, Case 2 achieved complete remission according to American Diabetes Association criteria, while Case 1 would also have achieved remission were it not for the continuation of metformin postoperatively. Insulin requirements and pill burden were markedly reduced in Case 3 after sleeve gastrectomy, although lack of remission was predictable given the longevity of type 2 diabetes mellitus and preoperative insulin dosage. In all three cases, human immunodeficiency virus status did not appear to be affected by the bariatric surgery which was supported by the postoperative stable CD4 count and undetectable viral load. Conclusions Bariatric surgery is a safe and effective treatment modality in patients who are human immunodeficiency virus positive with obesity and type 2 diabetes mellitus

Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers.

Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.This article is freely available via PubMed Central. Click on the 'Additional Link' above to access the full text