Characterization of HIV-1 envelopes in acutely and chronically infected injection drug users

BACKGROUND: Mucosally acquired human immunodeficiency virus type 1 (HIV-1) infection results from a limited number of variants, and these infecting strains potentially have unique properties, such as increased susceptibility to entry blockers, relative interferon-alpha (IFN-α) resistance, and replication differences in some primary cells. There is no data about the phenotypic properties of HIV-1 envelope variants found early after acquisition among subjects infected through injection drug use (IDU). For the first time, we compared the characteristics of virus envelopes among injection drug users sampled prior to seroconversion (HIV RNA+/Ab-), within 1 year (early), and more than 2 years (chronic) after estimated acquisition. RESULTS: Virus envelopes from 7 HIV RNA+/Ab- subjects possessed lower genetic diversity and divergence compared to 7 unrelated individuals sampled during the chronic phase of disease. Replication competent recombinant viruses incorporating the HIV RNA+/Ab- as compared to the chronic phase envelopes were significantly more sensitive to a CCR5 receptor inhibitor and IFN-α and showed a statistical trend toward greater sensitivity to a fusion blocker. The early as compared to chronic infection envelopes also demonstrated a statistical trend or significantly greater sensitivity to CCR5 and fusion inhibitor and IFN- α. The HIV RNA+/Ab- as compared to chronic envelope viruses replicated to a lower extent in mature monocyte derived dendritic cells – CD4+ T cell co-cultures, but there were no significant replication differences in other primary cells among the viruses with envelopes from the 3 different stages of infection. CONCLUSIONS: Similar to mucosal acquisition, HIV-1 envelope quasispecies present in injection drug users prior to seroconversion have unique phenotypic properties compared to those circulating during the chronic phase of disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0106-8) contains supplementary material, which is available to authorized users

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration

An analysis of fast photochemistry over high northern latitudes during spring and summer using in-situ observations from ARCTAS and TOPSE

Observations of chemical constituents and meteorological quantities obtained during the two Arctic phases of the airborne campaign ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) are analyzed using an observationally constrained steady state box model. Measurements of OH and HO2 from the Penn State ATHOS instrument are compared to model predictions. Forty percent of OH measurements below 2 km are at the limit of detection during the spring phase (ARCTAS-A). While the median observed-to-calculated ratio is near one, both the scatter of observations and the model uncertainty for OH are at the magnitude of ambient values. During the summer phase (ARCTAS-B), model predictions of OH are biased low relative to observations and demonstrate a high sensitivity to the level of uncertainty in NO observations. Predictions of HO2 using observed CH2O and H2O2 as model constraints are up to a factor of two larger than observed. A temperature-dependent terminal loss rate of HO2 to aerosol recently proposed in the literature is shown to be insufficient to reconcile these differences. A comparison of ARCTAS-A to the high latitude springtime portion of the 2000 TOPSE campaign (Tropospheric Ozone Production about the Spring Equinox) shows similar meteorological and chemical environments with the exception of peroxides; observations of H2O2 during ARCTAS-A were 2.5 to 3 times larger than those during TOPSE. The cause of this difference in peroxides remains unresolved and has important implications for the Arctic HOx budget. Unconstrained model predictions for both phases indicate photochemistry alone is unable to simultaneously sustain observed levels of CH2O and H2O2; however when the model is constrained with observed CH2O, H2O2 predictions from a range of rainout parameterizations bracket its observations. A mechanism suitable to explain observed concentrations of CH2O is uncertain. Free tropospheric observations of acetaldehyde (CH3CHO) are 2–3 times larger than its predictions, though constraint of the model to those observations is sufficient to account for less than half of the deficit in predicted CH2O. The box model calculates gross O3 formation during spring to maximize from 1–4 km at 0.8 ppbv d−1, in agreement with estimates from TOPSE, and a gross production of 2–4 ppbv d−1 in the boundary layer and upper troposphere during summer. Use of the lower observed levels of HO2 in place of model predictions decreases the gross production by 25–50%. Net O3 production is near zero throughout the ARCTAS-A troposphere, and is 1–2 ppbv in the boundary layer and upper altitudes during ARCTAS-B

High Rate of Obesity-Associated Hypertension among Primary Schoolchildren in Sudan

Cardiovascular disease (CVD) frequently has roots in childhood, including following childhood-onset hypertension. Incidence of CVD has increased in developing countries in East Africa during recent urbanization. Effects of these shifts on childhood hypertension are unclear. Our objectives were to (1) Determine the prevalence of hypertension among primary schoolchildren in Khartoum, Sudan; (2) Determine whether hypertension in this setting is associated with obesity. We performed a cross sectional study of 6-12y children from two schools randomly selected in Khartoum, Sudan. Height, weight, BMI, BP and family history of hypertension were assessed. Age-, height- and gender-specific BP curves were used to determine pre-hypertension (90–95%) and hypertension (>95%). Of 304 children, 45 (14.8%) were overweight; 32 (10.5%) were obese; 15 (4.9%) were pre-hypertensive and 15 (4.9%) were hypertensive. Obesity but not family history of hypertension was associated with current hypertension. In multiple logistic regression, adjusting for family history, children who were obese had a relative-risk of 14.7 (CI 2.45-88.2) for systolic hypertension compared to normal-weight children. We conclude that overweight and obesity are highly prevalent among primary schoolchildren in urban Sudan and are strongly associated with hypertension. That obesity-associated cardiovascular sequelae exist in the developing world at young ages may be a harbinger of future CVD in sub-Saharan Africa

CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome.

Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interfered with interactions between the RNA-binding protein Raly and the CCR5 3' untranslated region, protecting CCR5 messenger RNA from Raly-mediated degradation. Reduction in CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ T cells with CCR5-tropic HIV in vitro. These data represent a rare determination of the functional importance of a genome-wide disease association where expression of a lncRNA affects HIV infection and disease progression

Classification of Aerosol Retrievals from Spaceborne Polarimetry Using a Multiparameter Algorithm

In this presentation, we demonstrate application of a new aerosol classification algorithm to retrievals from the POLDER-3 polarimter on the PARASOL spacecraft. Motivation and method: Since the development of global aerosol measurements by satellites and AERONET, classification of observed aerosols into several types (e.g., urban-industrial, biomass burning, mineral dust, maritime, and various subtypes or mixtures of these) has proven useful to: understanding aerosol sources, transformations, effects, and feedback mechanisms; improving accuracy of satellite retrievals and quantifying assessments of aerosol radiative impacts on climate

Langevin Simulation of Thermally Activated Magnetization Reversal in Nanoscale Pillars

Numerical solutions of the Landau-Lifshitz-Gilbert micromagnetic model incorporating thermal fluctuations and dipole-dipole interactions (calculated by the Fast Multipole Method) are presented for systems composed of nanoscale iron pillars of dimension 9 nm x 9 nm x 150 nm. Hysteresis loops generated under sinusoidally varying fields are obtained, while the coercive field is estimated to be 1979 $\pm$ 14 Oe using linear field sweeps at T=0 K. Thermal effects are essential to the relaxation of magnetization trapped in a metastable orientation, such as happens after a rapid reversal of an external magnetic field less than the coercive value. The distribution of switching times is compared to a simple analytic theory that describes reversal with nucleation at the ends of the nanomagnets. Results are also presented for arrays of nanomagnets oriented perpendicular to a flat substrate. Even at a separation of 300 nm, where the field from neighboring pillars is only $\sim$ 1 Oe, the interactions have a significant effect on the switching of the magnets.Comment: 19 pages RevTeX, including 12 figures, clarified discussion of numerical technique

KIR/HLA Pleiotropism: Protection against Both HIV and Opportunistic Infections

The compound genotype KIR3DS1/HLA-B Bw4-80I, which presumably favors natural killer cell activation, has been implicated in protection against HIV disease. We show that this genotype confers dual protection over the course of HIV disease; early direct containment of HIV viral load, and late specific defense against opportunistic infections, but not AIDS-related malignancies. The double protection of KIR3DS1/Bw4-80I in an etiologically complex disease such as AIDS, along with the disease specificity of its effects is conceptually novel and underscores the intricacy of host immunogenetics against HIV/AIDS