Effects of once-daily darunavir/ritonavir versus atazanavir/ritonavir on insulin sensitivity in HIV-infected persons over 48 weeks: results of an exploratory substudy of METABOLIK, a phase 4, randomized trial.

Background: The phase 4, METABOLIK trial demonstrated that changes in metabolic parameters with darunavir with low-dose ritonavir (DRV/r) were comparable to those observed with atazanavir with low-dose ritonavir (ATV/r). A comprehensive assessment of the effects of these agents on insulin sensitivity will provide additional, relevant clinical information.

Methods: In this substudy of METABOLIK, HIV-1-infected, antiretroviral agent-naïve male subjects aged ≥18 years with a viral load of >1,000 copies/mL were randomized to receive DRV/r 800/100 mg once daily (qd) or ATV/r 300/100 mg qd, both with a fixed dose of tenofovir disoproxil fumarate/emtricitabine 300/200 mg qd.

Outcomes in older versus younger patients over 96 weeks in HIV-1- infected patients treated with rilpivirine or efavirenz in ECHO and THRIVE.

Objectives: Increasing life expectancy of HIV-1-infected patients raises interest in how trial results apply to older patients. This post-hoc analysis evaluated potential differences in efficacy and safety in older (≥50 years) versus younger (<50 years) patients in the ECHO and THRIVE trials over 96 weeks.

Methods: HIV-infected, treatment-naïve adults were randomized to receive rilpivirine (RPV) or efavirenz (EFV), plus a background regimen.

Insights on GRACE (Gender, Race, And Clinical Experience) from the patient's perspective: GRACE participant survey.

The Gender, Race And Clinical Experience (GRACE) study was conducted between October 2006 and December 2008 to evaluate sex- and race-based differences in outcomes after treatment with a darunavir/ritonavir-based antiretroviral regimen. Between June 2010 and June 2011, former participants of the GRACE trial at participating sites were asked to complete a 40-item questionnaire as part of the GRACE Participant Survey study, with a primary objective of assessing patients' characteristics, experiences, and opinions about participation in GRACE. Of 243 potential survey respondents, 151 (62%) completed the survey.

Natural killer cells, glutathione, cytokines, and innate immunity against Mycobacterium tuberculosis.

It is becoming increasingly apparent that natural killer (NK) cells play a crucial role in innate defense mechanisms against Mycobacterium tuberculosis infection. Furthermore, NK cell functions are dependent on adequate levels of glutathione. In this study, we examined whether the NK cell-mediated growth control of intracellular M.

Characterization of a glutathione metabolic mutant of Mycobacterium tuberculosis and its resistance to glutathione and nitrosoglutathione.

Glutathione is a tripeptide and antioxidant, synthesized at high levels by cells during the production of reactive oxygen and nitrogen intermediates. Glutathione also serves as a carrier molecule for nitric oxide in the form of S-nitrosoglutathione. Previous studies from this laboratory have shown that glutathione and S-nitrosoglutathione are directly toxic to mycobacteria.

Glutathione and nitrosoglutathione in macrophage defense against Mycobacterium tuberculosis.

We demonstrate that Mycobacterium tuberculosis grown in vitro is sensitive to glutathione and its derivative S-nitrosoglutathione. Furthermore, our infection studies with J774.1 macrophages indicate that glutathione is essential for the control of the intracellular growth of M.

Nitric oxide regulation of L-arginine uptake in murine and human macrophages.

L-arginine uptake systems in macrophages play a role in regulating nitric oxide synthesis via the inducible L-arginine nitric oxide pathway. This paper describes the association of L-arginine transport with nitric oxide production in human peripheral blood monocyte-derived macrophages and in peritoneal macrophages from control and inducible nitric oxide synthase knock out C57BL6 mice. Experiments performed with human macrophages suggested that little or no nitric oxide was produced in human macrophages in vitro and that human macrophages exhibit a different arginine transport-specific response to stimuli compared with rodent macrophages.

Role of glutathione in macrophage control of mycobacteria.

Reactive oxygen and nitrogen intermediates are important antimicrobial defense mechanisms of macrophages and other phagocytic cells. While reactive nitrogen intermediates have been shown to play an important role in tuberculosis control in the murine system, their role in human disease is not clearly established. Glutathione, a tripeptide and antioxidant, is synthesized at high levels by cells during reactive oxygen intermediate and nitrogen intermediate production.