Prevalence and pathogenesis of diabetes mellitus in HIV-1 infection treated with combined antiretroviral therapy
ABSTRACT 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.
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- "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). "
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.Virology 10/2014; 471-473C:1-12. DOI:10.1016/j.virol.2014.08.016 · 3.28 Impact Factor
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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.01/2011; DOI:10.2147/RRED.S16496
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ABSTRACT: A prospective study was designed to evaluate the prevalence and determinants of glucose metabolism abnormalities (GMAs) among HIV-1-infected pregnant women receiving highly active antiretroviral therapy (HAART). Blood samples were collected in fasting conditions and following a 100 g oral glucose tolerance test among HIV-infected pregnant women consecutively followed at asingle HIV reference centre in 2001-2008. GMAs were defined by glucose intolerance(IGT) or gestational diabetes (GDM), according to the National Diabetes Data Group criteria. Predictors of GMAs were assessed in univariate and multivariate analyses. Overall, 78 women with no history of diabetes or GMAs were eligible for analysis. All were on stable HAART with either nevirapine or protease inhibitors (PIs) from at least 4 weeks at the time of sampling. GMAs during pregnancy were observed in 20 women (25.6%; GDM: 6, 7.7%; IGT: 14, 17.9%). In a multivariate analysis, after adjusting for age and ongoing antiretroviral treatment (PI or nevirapine), GMAs in pregnancy were significantly associated with HCV coinfection(adjusted odds ratio 4.16; 95% CI, 1.22-14.1;p = .022). No maternal or neonatalcomplications were observed. GMAs represent a relevant issue in the management of HIV-1-infected pregnant women. Our data suggest that these abnormalities are relatively common in this particular group. Women with HCV coinfection have an increased risk of developing GMAs during pregnancy and should be monitored for potential complications.HIV Clinical Trials 11/2009; 10(6):403-12. DOI:10.1310/hct1006-403 · 2.14 Impact Factor