The epidemiological impact of antiretroviral use predicted by mathematical models: a review

This review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented

Modelling the impact of antiretroviral use in resource-poor settings.

BACKGROUND: The anticipated scale-up of antiretroviral therapy (ART) in high-prevalence, resource-constrained settings requires operational research to guide policy on the design of treatment programmes. Mathematical models can explore the potential impacts of various treatment strategies, including timing of treatment initiation and provision of laboratory monitoring facilities, to complement evidence from pilot programmes. METHODS AND FINDINGS: A deterministic model of HIV transmission incorporating ART and stratifying infection progression into stages was constructed. The impact of ART was evaluated for various scenarios and treatment strategies, with different levels of coverage, patient eligibility, and other parameter values. These strategies included the provision of laboratory facilities that perform CD4 counts and viral load testing, and the timing of the stage of infection at which treatment is initiated. In our analysis, unlimited ART provision initiated at late-stage infection (AIDS) increased prevalence of HIV infection. The effect of additionally treating pre-AIDS patients depended on the behaviour change of treated patients. Different coverage levels for ART do not affect benefits such as life-years gained per person-year of treatment and have minimal effect on infections averted when treating AIDS patients only. Scaling up treatment of pre-AIDS patients resulted in more infections being averted per person-year of treatment, but the absolute number of infections averted remained small. As coverage increased in the models, the emergence and risk of spread of drug resistance increased. Withdrawal of failing treatment (clinical resurgence of symptoms), immunologic (CD4 count decline), or virologic failure (viral rebound) increased the number of infected individuals who could benefit from ART, but effectiveness per person is compromised. Only withdrawal at a very early stage of treatment failure, soon after viral rebound, would have a substantial impact on emergence of drug resistance. CONCLUSIONS: Our analysis found that ART cannot be seen as a direct transmission prevention measure, regardless of the degree of coverage. Counselling of patients to promote safe sexual practices is essential and must aim to effect long-term change. The chief aims of an ART programme, such as maximised number of patients treated or optimised treatment per patient, will determine which treatment strategy is most effective

Quantum vortex reconnections

We study reconnections of quantum vortices by numerically solving the governing Gross-Pitaevskii equation. We find that the minimum distance between vortices scales differently with time before and after the vortex reconnection. We also compute vortex reconnections using the Biot-Savart law for vortex filaments of infinitesimal thickness, and find that, in this model, reconnection are time-symmetric. We argue that the likely cause of the difference between the Gross-Pitaevskii model and the Biot-Savart model is the intense rarefaction wave which is radiated away from a Gross-Pitaeveskii reconnection. Finally we compare our results to experimental observations in superfluid helium, and discuss the different length scales probed by the two models and by experiments.Comment: 23 Pages, 12 Figure

The Kelvin-wave cascade in the vortex filament model

The energy transfer mechanism in zero temperature superfluid turbulence of helium-4 is still a widely debated topic. Currently, the main hypothesis is that weakly nonlinear interacting Kelvin waves transfer energy to sufficiently small scales such that energy is dissipated as heat via phonon excitations. Theoretically, there are at least two proposed theories for Kelvin-wave interactions. We perform the most comprehensive numerical simulation of weakly nonlinear interacting Kelvin-waves to date and show, using a specially designed numerical algorithm incorporating the full Biot-Savart equation, that our results are consistent with nonlocal six-wave Kelvin wave interactions as proposed by L'vov and Nazarenko.Comment: 6 pages, 6 figure

Aspects of the Mass Distribution of Interstellar Dust Grains in the Solar System from In-Situ Measurements

The in-situ detection of interstellar dust grains in the Solar System by the dust instruments on-board the Ulysses and Galileo spacecraft as well as the recent measurements of hyperbolic radar meteors give information on the properties of the interstellar solid particle population in the solar vicinity. Especially the distribution of grain masses is indicative of growth and destruction mechanisms that govern the grain evolution in the interstellar medium. The mass of an impacting dust grain is derived from its impact velocity and the amount of plasma generated by the impact. Because the initial velocity and the dynamics of interstellar particles in the Solar System are well known, we use an approximated theoretical instead of the measured impact velocity to derive the mass of interstellar grains from the Ulysses and Galileo in-situ data. The revised mass distributions are steeper and thus contain less large grains than the ones that use measured impact velocities, but large grains still contribute significantly to the overall mass of the detected grains. The flux of interstellar grains with masses $> 10^{-14} {\rm kg}$ is determined to be $1\cdot 10^{-6} {\rm m}^{-2} {\rm s}^{-1}$. The comparison of radar data with the extrapolation of the Ulysses and Galileo mass distribution indicates that the very large ($m > 10^{-10} {\rm kg}$) hyperbolic meteoroids detected by the radar are not kinematically related to the interstellar dust population detected by the spacecraft.Comment: 14 pages, 11 figures, to appear in JG

Modeling the Impact of Antiretroviral Use in Developing Countries

Bertozzi and Bautista-Arredondo discuss the implications of a new PLoS Medicine study that models the impact of antiretroviral drugs upon HIV transmission in developing countries

A note on the propagation of quantized vortex rings through a quantum turbulence tangle:energy transport or energy dissipation?

We investigate quantum vortex ring dynamics at scales smaller than the inter-vortex spacing in quantum turbulence. Through geometrical arguments and high-resolution numerical simulations, we examine the validity of simple estimates for the mean free path and the structure of vortex rings post-reconnection. We find that a large proportion of vortex rings remain coherent objects where approximately 75% of their energy is preserved. This leads us to consider the effectiveness of energy transport in turbulent tangles. Moreover, we show that in low density tangles, appropriate for the ultra-quantum regime, ring emission cannot be ruled out as an important mechanism for energy dissipation. However at higher vortex line densities, typically associated with the quasi-classical regime, loop emission is expected to make a negligible contribution to energy dissipation, even allowing for the fact that our work shows rings can survive multiple reconnection events. Hence the Kelvin wave cascade seems the most plausible mechanism leading to energy dissipatio

Effectiveness and safety of oral HIV preexposure prophylaxis for all populations.

ObjectivePreexposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP containing tenofovir disoproxil fumarate as an additional HIV prevention strategy in populations at substantial risk for HIV based on HIV acquisition, adverse events, drug resistance, sexual behavior, and reproductive health outcomes.DesignRigorous systematic review and meta-analysis.MethodsA comprehensive search strategy reviewed three electronic databases and conference abstracts through April 2015. Pooled effect estimates were calculated using random-effects meta-analysis.ResultsEighteen studies were included, comprising data from 39 articles and six conference abstracts. Across populations and PrEP regimens, PrEP significantly reduced the risk of HIV acquisition compared with placebo. Trials with PrEP use more than 70% demonstrated the highest PrEP effectiveness (risk ratio = 0.30, 95% confidence interval: 0.21-0.45, P < 0.001) compared with placebo. Trials with low PrEP use did not show a significantly protective effect. Adverse events were similar between PrEP and placebo groups. More cases of drug-resistant HIV infection were found among PrEP users who initiated PrEP while acutely HIV-infected, but incidence of acquiring drug-resistant HIV during PrEP use was low. Studies consistently found no association between PrEP use and changes in sexual risk behavior. PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness.ConclusionPrEP is protective against HIV infection across populations, presents few significant safety risks, and there is no evidence of behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV risk