Impact of High-Risk Sex and Focused Interventions in Heterosexual HIV Epidemics: A Systematic Review of Mathematical Models

Background: The core-group theory of sexually transmitted infections suggests that targeting prevention to high-risk groups (HRG) could be very effective. We aimed to quantify the contribution of heterosexual HRGs and the potential impact of focused interventions to HIV transmission in the wider community. Methods: We systematically identified studies published between 1980 and 2011. Studies were included if they used dynamical models of heterosexual HIV transmission, incorporated behavioural heterogeneity in risk, and provided at least one of the following primary estimates in the wider community (a) the population attributable fraction (PAF) of HIV infections due to HRGs, or (b) the number per capita or fraction of HIV infections averted, or change in HIV prevalence/incidence due to focused interventions. Findings: Of 267 selected articles, 22 were included. Four studies measured the PAF, and 20 studies measured intervention impact across 265 scenarios. In low-prevalence epidemics (≤5% HIV prevalen

The effect of the dynamical state of clusters on gas expulsion and infant mortality

The star formation efficiency (SFE) of a star cluster is thought to be the critical factor in determining if the cluster can survive for a significant (>50 Myr) time. There is an often quoted critical SFE of ~30 per cent for a cluster to survive gas expulsion. I reiterate that the SFE is not the critical factor, rather it is the dynamical state of the stars (as measured by their virial ratio) immediately before gas expulsion that is the critical factor. If the stars in a star cluster are born in an even slightly cold dynamical state then the survivability of a cluster can be greatly increased.Comment: 6 pages, 2 figures. Review talk given at the meeting on "Young massive star clusters - Initial conditions and environments", E. Perez, R. de Grijs, R. M. Gonzalez Delgado, eds., Granada (Spain), September 2007, Springer: Dordrecht. Replacement to correct mistake in a referenc

Past dynamics of HIV transmission among men who have sex with men in Montréal, Canada: a mathematical modeling study

BACKGROUND: Gay, bisexual, and other men who have sex with men (gbMSM) experience disproportionate risks of HIV acquisition and transmission. In 2017, Montréal became the first Canadian Fast-Track City, setting the 2030 goal of zero new HIV infections. To inform local elimination efforts, we estimate the evolving role of prevention and sexual behaviours on HIV transmission dynamics among gbMSM in Montréal between 1975 and 2019. METHODS: Data from local bio-behavioural surveys were analyzed to develop, parameterize, and calibrate an agent-based model of sexual HIV transmission. Partnership dynamics, HIV's natural history, and treatment and prevention strategies were considered. The model simulations were analyzed to estimate the fraction of HIV acquisitions and transmissions attributable to specific groups, with a focus on age, sexual partnering level, and gaps in the HIV care-continuum. RESULTS: The model-estimated HIV incidence peaked in 1985 (2.3 per 100 person years (PY); 90% CrI: 1.4-2.9 per 100 PY) and decreased to 0.1 per 100 PY (90% CrI: 0.04-0.3 per 100 PY) in 2019. Between 2000-2017, the majority of HIV acquisitions and transmissions occurred among men aged 25-44 years, and men aged 35-44 thereafter. The unmet prevention needs of men with > 10 annual anal sex partners contributed 90-93% of transmissions and 67-73% of acquisitions annually. The primary stage of HIV played an increasing role over time, contributing to 11-22% of annual transmissions over 2000-2019. In 2019, approximately 70% of transmission events occurred from men who had discontinued, or never initiated antiretroviral therapy. CONCLUSIONS: The evolving HIV landscape has contributed to the declining HIV incidence among gbMSM in Montréal. The shifting dynamics identified in this study highlight the need for continued population-level surveillance to identify gaps in the HIV care continuum and core groups on which to prioritize elimination efforts

Dynamic Evolution of a Quasi-Spherical General Polytropic Magnetofluid with Self-Gravity

In various astrophysical contexts, we analyze self-similar behaviours of magnetohydrodynamic (MHD) evolution of a quasi-spherical polytropic magnetized gas under self-gravity with the specific entropy conserved along streamlines. In particular, this MHD model analysis frees the scaling parameter $n$ in the conventional polytropic self-similar transformation from the constraint of $n+\gamma=2$ with $\gamma$ being the polytropic index and therefore substantially generalizes earlier analysis results on polytropic gas dynamics that has a constant specific entropy everywhere in space at all time. On the basis of the self-similar nonlinear MHD ordinary differential equations, we examine behaviours of the magnetosonic critical curves, the MHD shock conditions, and various asymptotic solutions. We then construct global semi-complete self-similar MHD solutions using a combination of analytical and numerical means and indicate plausible astrophysical applications of these magnetized flow solutions with or without MHD shocks.Comment: 21 pages, 7 figures, accepted for publication in APS

Population-level impact of expanding PrEP coverage by offering long-acting injectable PrEP to MSM in three high-resource settings: a model comparison analysis

INTRODUCTION: Long-acting injectable cabotegravir (CAB-LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB-LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. METHODS: Three risk-stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person-years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB-LA users and by switching different proportions of TDF/FTC users to CAB-LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. RESULTS: Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB-LA users among PrEP-eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5-10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP-indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. CONCLUSIONS: Achieving high PrEP coverage by offering CAB-LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands)

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

Spiral anchoring in anisotropic media with multiple inhomogeneities: a dynamical system approach

Various PDE models have been suggested in order to explain and predict the dynamics of spiral waves in excitable media. In two landmark papers, Barkley noticed that some of the behaviour could be explained by the inherent Euclidean symmetry of these models. LeBlanc and Wulff then introduced forced Euclidean symmetry-breaking (FESB) to the analysis, in the form of individual translational symmetry-breaking (TSB) perturbations and rotational symmetry-breaking (RSB) perturbations; in either case, it is shown that spiral anchoring is a direct consequence of the FESB. In this article, we provide a characterization of spiral anchoring when two perturbations, a TSB term and a RSB term, are combined, where the TSB term is centered at the origin and the RSB term preserves rotations by multiples of $\frac{2\pi}{\jmath^*}$, where $\jmath^*\geq 1$ is an integer. When $\jmath^*>1$ (such as in a modified bidomain model), it is shown that spirals anchor at the origin, but when $\jmath^* =1$ (such as in a planar reaction-diffusion-advection system), spirals generically anchor away from the origin.Comment: Revised versio

HIV Epidemic Appraisals for Assisting in the Design of Effective Prevention Programmes: Shifting the Paradigm Back to Basics

To design HIV prevention programmes, it is critical to understand the temporal and geographic aspects of the local epidemic and to address the key behaviours that drive HIV transmission. Two methods have been developed to appraise HIV epidemics and guide prevention strategies. The numerical proxy method classifies epidemics based on current HIV prevalence thresholds. The Modes of Transmission (MOT) model estimates the distribution of incidence over one year among risk-groups. Both methods focus on the current state of an epidemic and provide short-term metrics which may not capture the epidemiologic drivers. Through a detailed analysis of country and sub-national data, we explore the limitations of the two traditional methods and propose an alternative approach.We compared outputs of the traditional methods in five countries for which results were published, and applied the numeric and MOT model to India and six districts within India. We discovered three limitations of the current methods for epidemic appraisal: (1) their results failed to identify the key behaviours that drive the epidemic; (2) they were difficult to apply to local epidemics with heterogeneity across district-level administrative units; and (3) the MOT model was highly sensitive to input parameters, many of which required extraction from non-regional sources. We developed an alternative decision-tree framework for HIV epidemic appraisals, based on a qualitative understanding of epidemiologic drivers, and demonstrated its applicability in India. The alternative framework offered a logical algorithm to characterize epidemics; it required minimal but key data.Traditional appraisals that utilize the distribution of prevalent and incident HIV infections in the short-term could misguide prevention priorities and potentially impede efforts to halt the trajectory of the HIV epidemic. An approach that characterizes local transmission dynamics provides a potentially more effective tool with which policy makers can design intervention programmes