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

NASA's Black Marble Nighttime Lights Product Suite

NASA's Black Marble nighttime lights product suite (VNP46) is available at 500 meters resolution since January 2012 with data from the Visible Infrared Imaging Radiometer Suite (VIIRS) Day/Night Band (DNB) onboard the Suomi National Polar-orbiting Platform (SNPP). The retrieval algorithm, developed and implemented for routine global processing at NASA's Land Science Investigator-led Processing System (SIPS), utilizes all high-quality, cloud-free, atmospheric-, terrain-, vegetation-, snow-, lunar-, and stray light-corrected radiances to estimate daily nighttime lights (NTL) and other intrinsic surface optical properties. Key algorithm enhancements include: (1) lunar irradiance modeling to resolve non-linear changes in phase and libration; (2) vector radiative transfer and lunar bidirectional surface anisotropic reflectance modeling to correct for atmospheric and BRDF (Bidirectional Reflectance Distribution Function) effects; (3) geometric-optical and canopy radiative transfer modeling to account for seasonal variations in NTL; and (4) temporal gap-filling to reduce persistent data gaps. Extensive benchmark tests at representative spatial and temporal scales were conducted on the VNP46 time series record to characterize the uncertainties stemming from upstream data sources. Initial validation results are presented together with example case studies illustrating the scientific utility of the products. This includes an evaluation of temporal patterns of NTL dynamics associated with urbanization, socioeconomic variability, cultural characteristics, and displaced populations affected by conflict. Current and planned activities under the Group on Earth Observations (GEO) Human Planet Initiative are aimed at evaluating the products at different geographic locations and time periods representing the full range of retrieval conditions