http://precedings.nature.com/tags/HIV Recently posted documents tagged with 'HIV' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/3917/version/1 Recently Granich et al. at the World Health Organization (WHO) concluded, using mathematical modeling, that HIV epidemics could be eliminated within a decade. They assumed all individuals would be tested annually and every infected individual (regardless of stage of infection) would be put on treatment. Based on this modeling study the WHO is considering using universal testing and treatment as an HIV elimination strategy. Here we examine the study by Granich et al. and assess its validity. We present new analyses of their model by varying assumptions and parameter values. We find that under certain very optimistic assumptions HIV elimination would be (theoretically) possible, but it would take at least 70 years. To obtain this result we assumed ~65% of symptomatic and ~20% of asymptomatic individuals would be treated per year; ARVs would reduce infectivity of treated individuals a hundred fold, and only 5% of symptomatic individuals would give up treatment per year. Even under optimistic assumptions we find elimination to be unlikely. For example, we show if ~65% of symptomatic individuals are treated per year and treated individuals are completely noninfectious, HIV will remain endemic with a prevalence of 34% and an incidence of 2% per year. We conclude that the model developed by Granich et al., when used with realistic parameter values, does not show HIV elimination is possible. However our modeling results show treatment could act as an effective prevention tool and significantly reduce transmission, even if only symptomatic individuals receive ARVs. Treatment should first, and foremost, be used for therapeutic purposes. Hence, we recommend – when resources are limited – targeting those in need of treatment. Such a strategy would be ethical, feasible and epidemiologically sound. We advise that models used as health policy tools should be carefully evaluated and their results interpreted with caution. http://precedings.nature.com/documents/3917/version/1 Thu, 29 Oct 2009 14:56:08 UTC Voluntary universal testing and treatment is unlikely to lead to HIV elimination: a modeling analysis hdl:10101/npre.2009.3917.1 2009-10-29 Nature Precedings 2009-10-29T14:56:08Z Manuscript Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2007.1299.1 The successful use of small interfering RNAs (siRNAs) for therapeutic purposes requires safe and efficient delivery to specific cells and tissues. Here we demonstrate cell type-specific delivery of anti-HIV siRNAs via fusion to an anti-gp120 aptamer. The envelope glycoprotein is expressed on the surface of HIV-1 infected cells, allowing binding and interalization of the aptamer-siRNA chimeric molecules. We demonstrate that the anti-gp120 aptamer-siRNA chimera is specifically taken up by cells expressing HIV-1 gp120, and the appended siRNA is processed by Dicer, releasing an anti-tat/rev siRNA which in turn inhibits HIV replication. We show for the first time a dual functioning aptamer-siRNA chimera in which both the aptamer and the siRNA portions have potent anti-HIV activities and that gp120 expressed on the surface of HIV infected cells can be used for aptamer mediated delivery of anti-HIV siRNAs. http://dx.doi.org/10.1038/npre.2007.1299.1 Wed, 14 Nov 2007 20:51:10 UTC Novel Cell type-specific aptamer-siRNA delivery system for HIV-1 therapy doi:10.1038/npre.2007.1299.1 2007-11-14 John Rossi Nature Precedings 2007-11-14T20:51:10Z Manuscript Biotechnology Molecular Cell Biology http://creativecommons.org/licenses/by/2.5/ http://precedings.nature.com/documents/1198/version/1 Steady-state behavior and bistability have been proposed as mechanisms for decision-making in gene circuits. However, transient gene expression has also been proposed to control cell fate with the decision arbitrated by the lifetime of the expression transient. Here, we report that transcriptional positive-feedback plays a critical role in determining HIV infected cell-fate by extending the duration of Tat expression transients far beyond what protein half-life modulation can achieve. To directly quantify feedback strength and its effects on the duration of Tat transcriptional pulses, we exploit the noise inherent to gene-expression and measure shifts in the autocorrelation of expression noise. The results indicate that transcriptional positive-feedback extends the single-cell Tat expression lifetime by ~6-fold for both minimal Tat circuits and full-length, actively-replicating HIV-1. Importantly, artificial weakening of Tat positive-feedback shortened the duration of Tat expression transients and biased the probability in favor of latency. Thus, transcriptional positive-feedback appears to modulate transient expression lifetime and thereby control cell-fate in HIV. http://precedings.nature.com/documents/1198/version/1 Mon, 01 Oct 2007 20:13:11 UTC Transient-mediated fate determination in a transcriptional circuit of HIV hdl:10101/npre.2007.1198.1 2007-10-01 Leor Weinberger Nature Precedings 2007-10-01T20:13:11Z Manuscript Biotechnology Genetics & Genomics Molecular Cell Biology http://creativecommons.org/licenses/by/2.5/