Viral dynamics in human immunodeficiency virus type 1 infection.
ABSTRACT The dynamics of HIV-1 replication in vivo are largely unknown yet they are critical to our understanding of disease pathogenesis. Experimental drugs that are potent inhibitors of viral replication can be used to show that the composite lifespan of plasma virus and virus-producing cells is remarkably short (half-life approximately 2 days). Almost complete replacement of wild-type virus in plasma by drug-resistant variants occurs after fourteen days, indicating that HIV-1 viraemia is sustained primarily by a dynamic process involving continuous rounds of de novo virus infection and replication and rapid cell turnover.
SourceAvailable from: Preeti Saini[Show abstract] [Hide abstract]
ABSTRACT: The emerging drug resistance towards anti-HIV compounds attracted the attention of scientific community. Development of potent anti-HIV therapy using non-nucleoside reverse transcriptase inhibitors (NNRTIs) known to be a promising strategy. Although NNRTIs has great importance in HIV-1 treatment and prevention but their mechanism of action has not yet been studied in detail. The present review discusses cellular interactions of HIV-1 followed by the FDA approved anti-HIV-1 chemotherapy. The review highlights the importance of NNRTIs and their mechanism of action in HIV-1 treatment. Also the current challenges and future prospective of NNRTIs to prevent HIV-1infection are well addressed so as to propose the development of novel therapeutic strategies for its treatment.
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ABSTRACT: We propose an stochastic model of HIV-1 infection dynamics under HAART in order to analyse the origin and dynamics of the so-called viral blips, i.e. episodes of transient viremia that occur in the phase of where the disease remains in a latent state during which the viral load raises above the detection limit of standard clinical assays. Based on prior work in the subject, we consider an infection model in which latently infected cell compartment sustains a residual (latent) infection over long periods of time. Unlike previous models, we include the effects of inhomogeneities in cell and virus concentration in the blood stream. We further consider the effect of burst virion production. By comparing with the experimental results obtained during an study in which intensive sampling was carried out on HIV-1-infected patients undergoing HAART over a long period of time, we conclude that our model supports the hypothesis that viral blips are consistent with random fluctuations around the average viral load. We further observe that agreement between our simulation results and the blip statistics obtained in the aformentioned study improves when burst virion production is considered. We also study the effect of sample manipulation artifacts on the results produced by our model, in particular, that of the post-extraction handling time, i.e. the time elapsed between sample extraction and actual test. Our results support the notion that the statistics of viral blips can be critically affected by such artifacts.Journal of Theoretical Biology 02/2015; DOI:10.1016/j.jtbi.2015.02.001 · 2.35 Impact Factor
Conference Paper: A Mathematical Study of Combined Use of Anti-HIV Drugs and a Mutagen[Show abstract] [Hide abstract]
ABSTRACT: The multidrug therapy for acquired immunodeficiency syndrome (AIDS) is efficacious in suppressing viral load, but it is an inappropriate treatment for AIDS patients suffering from side effects of anti-human immunodeficiency virus (HIV) drugs or who have developed resistance against these drugs. To cure these patients, alternative AIDS therapy is necessary. In a previous study 1, we discussed the availability of an alternative AIDS treatment that plunges viral activities into chaos by inducing excessive mutations by mutagenic activity in the HIV RNA genome and established a theoretical basis for its successful use in treatment. However concurrently mathematical analyses revealed treatment is only successful when the virulence of a virus was relatively low. In this study, we develop a new treatment to tackle HIV that has high virus virulence by examining the combined effects of a mutagenic agent and existing anti-HIV drugs. The drugs used include a reverse transcriptase inhibitor and a protease inhibitor. We prove that a therapy combining drug treatments with a mutagen is superior for its capacity to handle HIV with high virulence and its shorter treatment duration.Knowledge-Based and Intelligent Information & Engineering Systems 18th Annual Conference, KES-2014, Gdynia, Poland; 09/2014