Prevalence and Pathogenesis of Diabetes Mellitus in HIV-1 Infection Treated With Combined Antiretroviral Therapy
Diabetes and Obesity Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. JAIDS Journal of Acquired Immune Deficiency Syndromes
(Impact Factor: 4.56).
03/2009; 50(5):499-505. DOI: 10.1097/QAI.0b013e31819c291b
Combined antiretroviral therapy (cART) in the treatment of HIV-1 infection confers significant survival benefit and, by immunoreconstitution, has altered the natural history of this life-threatening disease. Metabolic complications of cART include hyperlipidemia, insulin resistance, and lipodystrophy, with resultant increases in risk for type 2 diabetes and cardiovascular disease. These diseases will present new challenges in the management of HIV infection. This article reviews the prevalence of diabetes mellitus and its antecedents in HIV-infected patients treated with cART. It also reviews the current understanding of mechanisms involved in the pathogenesis of type 2 diabetes in cART considering insulin resistance and insulin secretion, both requisites for the development of type 2 diabetes mellitus.
Available from: Tracy Fischer
- "HIV infection, itself, can share these common pathways and is associated with increased vascular morbidity through elevated levels of inflammatory and procoagulant factors, atherogenesis, and endothelial alterations [6,125126127. In addition, the role of antiretroviral therapy, especially protease inhibitors, has been implicated in the development of metabolic syndrome with insulin resistance, dyslipidemia, and hypertension [26, 28,128129130131. If obesity and cigarette smoking are included in the risk profiling for vascular disease, HIV populations are population-matched in obesity rates and exceed peer groups in smoking frequency [20, 38, 132]. "
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ABSTRACT: The prevalence of HIV (human immunodeficiency virus) associated neurocognitive disorders (HAND) will undoubtedly increase with the improved longevity of HIV-infected persons. HIV infection, itself, as well as multiple physiologic and psychosocial factors can contribute to cognitive impairment and neurologic complications. These comorbidities confound the diagnosis, assessment, and interventions for neurocognitive disorders. In this review, we discuss the role of several key comorbid factors that may contribute significantly to the development and progression of HIV-related neurocognitive impairment, as well as the current status of diagnostic strategies aimed at identifying HIV-infected individuals with impaired cognition and future research priorities and challenges.
Available from: Alberto Bosque
- "This necessitates continuous therapy and creates several problems, including high cost, poor adherence, and drug resistance . Even in adherent patients, chronic exposure to both latent virus production and antiretrovirals appears to increase the risk of developing non-AIDS defining illnesses such as cardiovascular disease, diabetes, liver disease, and cancer (Bedimo, 2008; Samaras, 2009; Weber et al., 2006). For these reasons, one of the major goals of HIV-1 antiretroviral research is to develop a therapy that targets latently infected cells to facilitate drug-free remission of disease (Richman et al., 2009). "
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ABSTRACT: Long-lived pools of latently infected cells are a significant barrier to the development of a cure for HIV-1 infection. A better understanding of the mechanisms of reactivation from latency is needed to facilitate the development of novel therapies that address this problem. Here we show that chemical inhibitors of the sulfonation pathway prevent virus reactivation, both in latently infected J-Lat and U1 cell lines and in a primary human CD4+ T cell model of latency. In each of these models, sulfonation inhibitors decreased transcription initiation from the HIV-1 promoter. These inhibitors block transcription initiation at a step that lies downstream of nucleosome remodeling and affects RNA polymerase II recruitment to the viral promoter. These results suggest that the sulfonation pathway acts by a novel mechanism to regulate efficient virus transcription initiation during reactivation from latency, and further that augmentation of this pathway could be therapeutically useful.
Available from: Eswar K Kilari
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ABSTRACT: 3 cytel statistical software and services Pvt Ltd, Pune, Maharashtra, india correspondence: shaik Mastan senior Pharmacokineticist, cytel statistical software and services Pvt Ltd (subsidiary of cytel inc., UsA), 8th Floor, siddharth Towers, Kothrud, Abstract: The objective of this study was to investigate the effect of protease inhibitors (indinavir and ritonavir) on the pharmacokinetics of gliclazide in rabbits and to evaluate the mechanism of interaction of the combination. Studies in rabbits were conducted with oral doses of gliclazide, selected protease inhibitor, and their combination with a 1-week washout period between each treatment (single dose followed by multiple dose treatment). Blood samples were collected at regular time intervals by marginal ear vein puncture and serum gliclazide levels were analyzed by high-pressure liquid chromatography. Pharmacokinetic analysis was performed by noncompartmental analysis using WinNonlin Software. In combination, ritonavir significantly increased serum gliclazide levels and altered the pharmacokinetic parameters of gliclazide in rabbits while indinavir had no significant effect. The percentage increase of serum gliclazide level was 22.34% and 27.78% following single-dose and multiple-dose treatment of ritonavir, respectively. The interaction of ritonavir with gliclazide is pharmacokinetic at a metabolic level (by CYP3A4 inhibition) in normal rabbits, while the interaction of indinavir with gliclazide is pharmacodynamic, which needs dose adjustment, and care should be taken when these combinations are prescribed for their clinical benefit in diabetic patients.
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