Does choice of antiretroviral drugs matter for inflammation?

Introduction: The massive implementation of combination antiretroviral therapy (cART) has forever changed the landscape of HIV infection. This unprecedented success has turned HIV infection into a manageable chronic disease. The increased survival of people living with HIV is, however, shadowed by a high burden of aging-related comorbidities. The pathogenic basis underlying this excess of co-morbid conditions is most likely a persistent inflammatory and immune activation state, despite an optimal control of HIV replication, which in turn has largely been attributed to bacterial or bacterial products translocation from the gut.

Area covered: This review is focused on the relationship between cART and the chronic inflammatory and immune activation status in otherwise virologically well-controlled people living with HIV (PLWH). Particular focus will be placed on the differences, if any, between distinct cART modalities, with emphasis on less-drug cART regimens, and especially on dual therapies.

Expert opinion: Research to address the increased inflammatory and immune activation status of cART-treated, HIV-infected patients, should focus on adjuvant means of therapy, rather than on the cART regime itself. With current antiretrovirals, no difference between dual and triple regimens has been demonstrated, provided that virological and immunological outcomes be non-inferior.     

The response of γ vitamin E to varying dosages of α vitamin E plus vitamin C

Vitamin E has been studied extensively in the prevention of atherosclerosis. Cross-sectional population studies as well as randomized controlled intervention trials have demonstrated conflicting results. A recent meta-analysis of these trials has emphasized the ineffectiveness of vitamin E in atherosclerosis prevention, with a possibility of harm at higher dosages. However, vitamin E has several isomers, with the α form being available via dietary supplements and the γ form being available via dietary foodstuffs. The γ form of vitamin E demonstrates several superior properties (such as trapping reactive nitrogen species and detoxifying nitrogen dioxide) compared with α vitamin E. All clinical trials have used the α isomer, with little concern that this isomer of vitamin E may actually suppress the γ isomer of vitamin E. We undertook a dose-response study in volunteers with type 2 diabetes mellitus to include all the dosages of α vitamin E that have been used in cardiovascular prevention trials to determine the effect of α vitamin E on γ vitamin E. We also assessed the effect of α vitamin E on several traditional markers of atherosclerotic risk. We added vitamin C to the vitamin E because several clinical trials included this vitamin to enhance the antioxidant effects of α vitamin E. Volunteers received, in randomized order for a 2-week period, one of the following vitamin dosage arms: (1) no vitamins, (2) low-dose supplemental vitamins E plus C, (3) medium-dose supplemental vitamins E plus C, and (4) high-dose supplemental vitamins E plus C. Blood levels of both α and γ vitamin E were measured as well as surrogate markers of oxidative stress, hypercoagulation, and inflammation during a high-fat atherogenic meal (to increase the ambient oxidative stress level during the study). The results demonstrate that α vitamin E levels increased in proportion to the dose administered. However, at every dose of α vitamin E, γ vitamin E concentration was significantly suppressed. No beneficial changes in surrogate markers of atherosclerosis were observed, consistent with the negative results of prospective clinical trials using α vitamin E. Our results suggest that all prospective cardiovascular clinical trials that used vitamin E supplementation actually suppressed the beneficial antioxidant γ isomer of vitamin E. No beneficial effects on several potential cardiovascular risk factors were observed, even when the vitamin E was supplemented with vitamin C. If a standardized preparation of γ vitamin E (without the α isomer) becomes available, the effects of γ vitamin E on atherosclerotic risk will warrant additional studies.     

Cardiac MRI in the management of congenital heart disease in children, adolescents, and young adults

Recent advances in MRI have made this modality an important tool for evaluating heart disease. Faster scanning techniques, high spatial resolution, lack of ionizing radiation, lack of dependence on contrast material, and capability for functional imaging have made it an emerging noninvasive diagnostic tool with great potential in younger patients with heart disease. This article discusses the role of cardiac MRI, methods of evaluation, and newer application of MRI in evaluating congenital heart disease in pediatric and young adult patients.