Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136

Stress analysis of cylindrical pressure vessels with closely spaced nozzles by the finite-element method. Volume 1. Stress analysis of vessels with two closely spaced nozzles under internal pressure. [BWR; PWR; MULT-NOZZLE code]

A finite-element computer program, MULT-NOZZLE, was developed for the stress analysis of cylindrical pressure vessels with two or three closely spaced reinforced nozzles. MULT-NOZZLE consists of two modules which may be operated independently. The first module, FEMG, automatically prepares a finite-element mesh including the nodal point coordinates, finite-element connectivities, mesh options, and boundary value specifications for input to the finite-element solution module SAP3M. SAP3M, which is a modified and improved version of the SAP3 computer program, computes the nodal point displacements and stress tensor components, and prints and/or stores the results for later postprocessing. The accuracy of the SAP3M module is demonstrated by comparison studies of two classical theory-of-elasticity problems: a simply supported beam and a thick-walled ring under internal pressure loading. A complete discussion of MULT-NOZZLE is presented in four volumes. Volume develops the finite-element idealization for pressure vessels with two idential radially attached closely spaced nozzles for internal pressure loading. The nozzles may be unreinforced or fully reinforced according to the rules of the ASME Boiler and Pressure Vessel Code and may be located in either a longitudinal or a transverse plane of the vessel. Validation of the program for analyzing this type of structure is demonstrated by the analysis of three two-nozzle pressure vessel models and comparison of results with experimental data. In general, quite satisfactory results were obtained

The Behavior Oriented Design of an Unreal Tournament Character

Abstract. This paper presents a case study for using a relatively recently developed methodology, Behavior Oriented Design, to develop an Intelligent Virtual Agent (IVA). Our usability study was conducted in Unreal Tournament using the game Capture The Flag. The final agent displays reasonably competent behavior: she is able to pursue multiple goals simultaneously and produce well-ordered behavior.

Where Should Complexity Go? Cooperation in Complex Agents with Minimal Communication

The `Radical Agent Concept&apos; in this chapter is that communication between agents in a MAS should be the simplest part of the system. When extensive real-time coordination between modules is required, then those modules should probably be considered elements of a single modular agent rather than as agents themselves. The advantage of this distinction is that system developers can then leverage standard software-engineering practices and more centralized coordination mechanisms to reduce the over-all complexity of the system. In this chapter I provide arguments for this point and also examples, both from nature and from my own research in building modular agents