Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201).

OBJECTIVES: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. METHODS: Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD\u27s 38/69/94/95/158/279). RESULTS: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) \u3e50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL \u3e50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. CONCLUSIONS: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT00084019

Issues and progress in the prediction of ocean submesoscale features and internal waves

Data-constrained dynamical ocean modeling for the purpose of detailed forecasting and prediction continues to evolve and improve in quality. Modeling methods and computational capabilities have each improved. The result is that mesoscale phenomena can be modeled with skill, given sufficient data. However, many submesoscale features are less well modeled and remain largely unpredicted from a deterministic event standpoint, and possibly also from a statistical property standpoint. A multi-institution project is underway with goals of uncovering more of the details of a few submesoscale processes, working toward better predictions of their occurrence and their variability. A further component of our project is application of the new ocean models to ocean acoustic modeling and prediction. This paper focuses on one portion of the ongoing work: Efforts to link nonhydrostatic-physics models of continental-shelf nonlinear internal wave evolution to data-driven regional models. Ocean front-related effects are also touched on.United States. Office of Naval Research (United States. Dept. of Defense. Multidisciplinary University Research Initiative (Ocean Acoustics Program Award N00014-11-1-0701))United States. Office of Naval Research (Grant N00014-12-1-0944)National Science Foundation (U.S.) (Grant OCE-1061160

Multiscale multiphysics data-informed modeling for three-dimensional ocean acoustic simulation and prediction

Author Posting. © Acoustical Society of America, 2019. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 146(3), (2019): 1996-2015, doi:10.1121/1.5126012.Three-dimensional (3D) underwater sound field computations have been used for a few decades to understand sound propagation effects above sloped seabeds and in areas with strong 3D temperature and salinity variations. For an approximate simulation of effects in nature, the necessary 3D sound-speed field can be made from snapshots of temperature and salinity from an operational data-driven regional ocean model. However, these models invariably have resolution constraints and physics approximations that exclude features that can have strong effects on acoustics, example features being strong submesoscale fronts and nonhydrostatic nonlinear internal waves (NNIWs). Here, work to predict NNIW fields to improve 3D acoustic forecasts using an NNIW model nested in a tide-inclusive data-assimilating regional model is reported. The work was initiated under the Integrated Ocean Dynamics and Acoustics project. The project investigated ocean dynamical processes that affect important details of sound-propagation, with a focus on those with strong intermittency (high kurtosis) that are challenging to predict deterministically. Strong internal tides and NNIW are two such phenomena, with the former being precursors to NNIW, often feeding energy to them. Successful aspects of the modeling are reported along with weaknesses and unresolved issues identified in the course of the work.This work was supported by Department of Defense Multidisciplinary University Initiative (MURI) Grant No. N00014-11-1-0701, managed by the Office of Naval Research Ocean Acoustics Program, and National Science Foundation Grant No. OCE-1060430. Final manuscript preparation was supported by ONR Ocean Acoustics Grant Nos. N00014-17-1-2624 and N00014-17-1-2692. P.F.J.L. also thanks ONR and NSF for research support under Grant Nos. N00014-13-1-0518 (Multi-DA) and OCE-1061160 (ShelfIT) to MIT, respectively. The MSEAS-based series of simulations for the New Jersey shelf region examined here was accelerated toward completion by the interest in realistic 3D acoustic fields expressed by Dr. Ivars Kirsteins at the Naval Undersea Warfare Center.2020-03-3

Perspectives of US women participating in a candidate PrEP study: adherence, acceptability and future use intentions

Introduction Limited data exist on acceptability of candidate pre‐exposure prophylaxis (PrEP) regimens among US women. We evaluated PrEP experiences, attitudes and future use intentions among sexually active women who completed the US‐based HIV Prevention Trials Network 069/AIDS Clinical Trials Group 5305 study. Methods Women participated in the study between March 2013 and November 2015. We analysed computer‐assisted self‐interview (CASI) surveys among 130 women and conducted in‐depth interviews among a subset of 26 women from three sites. Interviews were conducted in mid/late‐2015. Results Most women (57%) reported very good/excellent PrEP adherence on CASI, although 21% acknowledged over‐reporting adherence at least some of the time. Commitment to preventing HIV infection, a sense of ownership of the study, and keeping pills stored in a visible location facilitated adherence. Adherence barriers included “simply forgetting” and being away from home. Most women interviewed did not intend to use PrEP in the future because of lack of perceived need due to their own (as opposed to their partners’) low‐risk behaviour and concerns about affordability – but not because of side effects or other characteristics of the regimens. Conclusions Improving HIV prevention options for US women will require access to affordable PrEP as well as expanding women\u27s understanding of relationship‐ and community‐level factors that increase their risk of acquiring HIV

An Insight Into Cervical Cancer Screening and Treatment Capacity in Sub Saharan Africa.

OBJECTIVE Approximately 85% of cervical cancer cases and deaths occur in resource-constrained countries where best practices for prevention, particularly for women with HIV infection, still need to be developed. The aim of this study was to assess cervical cancer prevention capacity in select HIV clinics located in resource-constrained countries. MATERIALS AND METHODS A cross-sectional survey of sub-Saharan African sites of 4 National Institutes of Health-funded HIV/AIDS networks was conducted. Sites were surveyed on the availability of cervical cancer screening and treatment among women with HIV infection and without HIV infection. Descriptive statistics and χ or Fisher exact test were used as appropriate. RESULTS Fifty-one (65%) of 78 sites responded. Access to cervical cancer screening was reported by 49 sites (96%). Of these sites, 39 (80%) performed screening on-site. Central African sites were less likely to have screening on-site (p = .02) versus other areas. Visual inspection with acetic acid and Pap testing were the most commonly available on-site screening methods at 31 (79%) and 26 (67%) sites, respectively. High-risk HPV testing was available at 29% of sites with visual inspection with acetic acid and 50% of sites with Pap testing. Cryotherapy and radical hysterectomy were the most commonly available on-site treatment methods for premalignant and malignant lesions at 29 (74%) and 18 (46%) sites, respectively. CONCLUSIONS Despite limited resources, most sites surveyed had the capacity to perform cervical cancer screening and treatment. The existing infrastructure of HIV clinical and research sites may provide the ideal framework for scale-up of cervical cancer prevention in resource-constrained countries with a high burden of cervical dysplasia

Perspectives of US women participating in a candidate PrEP study: adherence, acceptability and future use intentions

IntroductionLimited data exist on acceptability of candidate preâ exposure prophylaxis (PrEP) regimens among US women. We evaluated PrEP experiences, attitudes and future use intentions among sexually active women who completed the USâ based HIV Prevention Trials Network 069/AIDS Clinical Trials Group 5305 study.MethodsWomen participated in the study between March 2013 and November 2015. We analysed computerâ assisted selfâ interview (CASI) surveys among 130 women and conducted inâ depth interviews among a subset of 26 women from three sites. Interviews were conducted in mid/lateâ 2015.ResultsMost women (57%) reported very good/excellent PrEP adherence on CASI, although 21% acknowledged overâ reporting adherence at least some of the time. Commitment to preventing HIV infection, a sense of ownership of the study, and keeping pills stored in a visible location facilitated adherence. Adherence barriers included â simply forgettingâ and being away from home. Most women interviewed did not intend to use PrEP in the future because of lack of perceived need due to their own (as opposed to their partnersâ ) lowâ risk behaviour and concerns about affordability â but not because of side effects or other characteristics of the regimens.DiscussionImproving HIV prevention options for US women will require access to affordable PrEP as well as expanding women’s understanding of relationshipâ and communityâ level factors that increase their risk of acquiring HIV.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148389/1/jia225247_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148389/2/jia225247.pd

HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial

Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral (ARV) regimens in treatment-experienced patients in the absence of data from randomized trials

The coupled boundary layers and air-sea transfer experiment in low winds

Author Posting. © American Meteorological Society, 2007. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 88 (2007): 341-356, doi:10.1175/bams-88-3-341.The Office of Naval Research's Coupled Boundary Layers and Air–Sea Transfer (CBLAST) program is being conducted to investigate the processes that couple the marine boundary layers and govern the exchange of heat, mass, and momentum across the air–sea interface. CBLAST-LOW was designed to investigate these processes at the low-wind extreme where the processes are often driven or strongly modulated by buoyant forcing. The focus was on conditions ranging from negligible wind stress, where buoyant forcing dominates, up to wind speeds where wave breaking and Langmuir circulations play a significant role in the exchange processes. The field program provided observations from a suite of platforms deployed in the coastal ocean south of Martha's Vineyard. Highlights from the measurement campaigns include direct measurement of the momentum and heat fluxes on both sides of the air–sea interface using a specially constructed Air–Sea Interaction Tower (ASIT), and quantification of regional oceanic variability over scales of O (1–104 mm) using a mesoscale mooring array, aircraft-borne remote sensors, drifters, and ship surveys. To our knowledge, the former represents the first successful attempt to directly and simultaneously measure the heat and momentum exchange on both sides of the air–sea interface. The latter provided a 3D picture of the oceanic boundary layer during the month-long main experiment. These observations have been combined with numerical models and direct numerical and large-eddy simulations to investigate the processes that couple the atmosphere and ocean under these conditions. For example, the oceanic measurements have been used in the Regional Ocean Modeling System (ROMS) to investigate the 3D evolution of regional ocean thermal stratification. The ultimate goal of these investigations is to incorporate improved parameterizations of these processes in coupled models such as the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS) to improve marine forecasts of wind, waves, and currents.This work was supported by the Office of Naval Research

Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305)

Maraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis