Supporting Treatment Adherence Readiness through Training (START) for patients with HIV on antiretroviral therapy: study protocol for a randomized controlled trial.

BackgroundFew HIV antiretroviral adherence interventions target patients before they start treatment, assess adherence readiness to determine the timing of treatment initiation, or tailor the amount of adherence support. The Supporting Treatment Adherence Readiness through Training (START) intervention, based on the information-motivation-behavioral skills model of behavior change, is designed to address these gaps with the inclusion of (1) brief pill-taking practice trials for enhancing pretreatment adherence counseling and providing a behavioral criterion for determining adherence readiness and the timing of treatment initiation and (2) a performance-driven dose regulation mechanism to tailor the amount of counseling to the individual needs of the patient and conserve resources. The primary aim of this randomized controlled trial is to examine the effects of START on antiretroviral adherence and HIV virologic suppression.Methods/designA sample of 240 patients will be randomized to receive START or usual care at one of two HIV clinics. Primary outcomes will be optimal dose-taking adherence (>85 % prescribed doses taken), as measured with electronic monitoring caps, and undetectable HIV viral load. Secondary outcomes will include dose-timing adherence (>85 % prescribed doses taken on time) and CD4 count. Primary endpoints will be month 6 (short-term effect) and month 24 (to test durability of effect), though electronic monitoring will be continuous and a fully battery of assessments will be administered every 6 months for 24 months.DiscussionIf efficacious and cost-effective, START will provide clinicians with a model for assessing patient adherence readiness and helping patients to achieve and sustain readiness and optimal treatment benefits.Trial registrationClinicalTrials.gov identifier NCT02329782 . Registered on 22 December 2014

Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons.

Objective The contribution of hepatitis C virus (HCV) infection to the risk of heart failure in human immunodeficiency virus (HIV)-coinfected persons is unknown. The objective was to characterize cardiac function and morphology in HIV-treated coinfected persons. Methods In a cross-sectional study, HIV-infected patients virologically suppressed on antiretroviral therapy without known cardiovascular disease or diabetes mellitus underwent cardiac magnetic resonance imaging and spectroscopy for measures of cardiac function, myocardial fibrosis, and steatosis. Results The study included 18 male patients with a median age of 44 years. Of these, 10 had untreated HCV coinfection and eight had HIV monoinfection. Global systolic and diastolic function in the cohort were normal, and median myocardial fat content was 0.48% (interquartile range 0.35-1.54). Left ventricular (LV) mass index and LV mass/volume ratio were significantly greater in the HIV/HCV-coinfected group compared with the HIV-monoinfected group. In the HIV-monoinfected group, there was more myocardial fibrosis as measured by extracellular volume fraction. Conclusions There were differences between HIV/HCV-coinfected and HIV-monoinfected patients in cardiac structure and morphology. Larger studies are needed to examine whether HIV and HCV independently contribute to mechanisms of heart failure

Topological Defects and Interactions in Nematic Emulsions

Inverse nematic emulsions in which surfactant-coated water droplets are dispersed in a nematic host fluid have distinctive properties that set them apart from dispersions of two isotropic fluids or of nematic droplets in an isotropic fluid. We present a comprehensive theoretical study of the distortions produced in the nematic host by the dispersed droplets and of solvent mediated dipolar interactions between droplets that lead to their experimentally observed chaining. A single droplet in a nematic host acts like a macroscopic hedgehog defect. Global boundary conditions force the nucleation of compensating topological defects in the nematic host. Using variational techniques, we show that in the lowest energy configuration, a single water droplet draws a single hedgehog out of the nematic host to form a tightly bound dipole. Configurations in which the water droplet is encircled by a disclination ring have higher energy. The droplet-dipole induces distortions in the nematic host that lead to an effective dipole-dipole interaction between droplets and hence to chaining.Comment: 17 double column pages prepared by RevTex, 15 eps figures included in text, 2 gif figures for Fig. 1

Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study.

OBJECTIVES: To examine whether the overall results of the CASTLE study pertain to both genders, we analysed the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir in 277 female and 606 male patients in the open-label, multinational trial over 96 weeks. The trial is registered with ClinicalTrials.gov, number NCT00272779. METHODS: Treatment-naive patients aged ≥ 18 years with HIV-1 RNA ≥ 5000 copies/mL were randomized to receive either atazanavir/ritonavir 300/100 mg once daily or lopinavir/ritonavir 400/100 mg twice daily, with fixed-dose tenofovir/emtricitabine 300/200 mg once daily. RESULTS: At week 96, confirmed virological response rates (HIV RNA \u3c50 copies\u3e/mL; intent-to-treat analysis) were higher in women and men receiving atazanavir/ritonavir than those receiving lopinavir/ritonavir and lower in women than men in both treatment arms (67% of women and 77% of men on atazanavir/ritonavir and 63% of women and 71% of men on lopinavir/ritonavir). These differences were not observed in the on-treatment analysis. Mean change in CD4 cell count from baseline to week 96 was 265 cells/mm(3) for women and 269 cells/mm(3) for men on atazanavir/ritonavir and 298 cells/mm(3) for women and 286 cells/mm(3) for men on lopinavir/ritonavir. Discontinuation rates were higher in women than men in each treatment arm (22% of women and 15% of men on atazanavir/ritonavir and 29% of women and 18% of men on lopinavir/ritonavir). In women and men, grade 2-4 nausea and diarrhoea were more frequent in the lopinavir/ritonavir group; jaundice and hyperbilirubinaemia occurred more frequently in the atazanavir/ritonavir group. CONCLUSIONS: Once-daily atazanavir/ritonavir is an effective and well-tolerated therapeutic option for women and men with HIV-1 infection. The sex-based differences in response may be due to higher discontinuation rates in women

Nutrition, diet and immunosenescence

Ageing is characterized by immunosenescence and the progressive decline in immunity in association with an increased frequency of infections and chronic disease. This complex process affects both the innate and adaptive immune systems with a progressive decline in most immune cell populations and defects in activation resulting in loss of function. Although host genetics and environmental factors, such as stress, exercise and diet can impact on the onset or course of immunosenescence, the mechanisms involved are largely unknown. This review focusses on identifying the most significant aspects of immunosenescence and on the evidence that nutritional intervention might delay this process, and consequently improve the quality of life of the elderly

The Platte as a Prairie River: A Response to Johnson and Boettcher

Johnson and Boettcher (2000) question the status of the presettlement Platte River as a prairie river, and they argue that it was a wooded river traversing a prairie landscape. Here we review evidence in support of the prairie river concept, suggesting the channels of the Platte were predominantly open and largely absent of trees. Direct support for a prairie river is found in the detailed map drawn by Lieutenant Woodbury in locating the site for Fort Kearny in 1847. Woodbury showed a thin strip of timber, located in an area that appeared to be elevated above the influence of active river flows. Woodbury also illustrated the main channel as having vegetated islands only in one location, with only a scattering [of] trees along the banks. Historical accounts, an examination of historical perspectives, the distribution of land survey witness trees, a lack of regeneration of trees following supposed deforestation, and population changes in bird distributions over the past 100 years also support the prairie river concept. We argue woodland development is not true restoration in this area. Given current conditions, we suggest that long term management should be for a mosaic of habitats for migratory birds and other species including 10% open river channel in the Big Bend reach of the Platte River in central Nebraska

HIV-1 protease inhibitors and clinical malaria: A secondary analysis of the AIDS Clinical Trials Group A5208 study

HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted. Copyrigh