Wei, X. et al. Viral dynamics in human immunodeficiency virus type I infection. Nature 373, 117−122
Division of Hematology/Oncology, University of Alabama at Birmingham 35294. Nature
(Impact Factor: 41.46).
02/1995; 373(6510):117-22. DOI: 10.1038/373117a0
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.
Available from: Sam T Douthwaite
- "ETECTION and quantification of HIV-1 is important not only for diagnosis of HIV-1 infections but also for management of HIV-1 patients  and research applications , . Quantitative measurements of HIV in the peripheral blood has shown that higher viral loads may be correlated with increased risk of clinical progression of HIV-associated disease, and reductions in plasma virus levels may be associated with decreased risk of clinical progression -. "
Available from: Abdon Atangana
- "The infection results in high T-cell activation and turnover. An immediately intuitive assumption is that HIV-mediated destruction of CD4 + cells directly reduces the number of these cells and that the high turnover rates of T cells and the slow progression to AIDS reflect a long but eventually lost struggle of the immune system to replace killed cells in its effort to maintain T-cell homeostasis    . However, HIV mainly infects activated CD4 + cells, and activated cells normally follow different dynamics than cells that belong to resting populations whose numbers are controlled by homeostatic mechanisms. "
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ABSTRACT: An analysis of the model underpinning the description of the spread of HIV infection of CD4
T cells is examined in detail in this work. Investigations of the disease free and endemic equilibrium are done using the method of Jacobian matrix. An iteration technique, namely, the homotopy decomposition method (HDM), is implemented to give an approximate solution of nonlinear ordinary differential equation systems. The technique is described and illustrated with numerical examples. The approximated solution obtained via HDM is compared with those obtained via other methods to prove the trustworthiness of HDM. Moreover, the lessening and simplicity in calculations furnish HDM with a broader applicability.
Available from: Gabriel E Leventhal
- "The genetic diversity of HIV within a patient is large as HIV is prone to errors during replication (Overbaugh and Bangham, 2001; Rambaut et al., 2004). Furthermore, the virus population has a high turnover with a mean half-life of 1–2 days (Coffin, 1995; Ho et al., 1995; Perelson et al., 1996; Wei et al., 1995). The high heritability , the fitness differences between virus genotypes, the large virus population size within a host, the high mutation rate and the short generation time together lead to the expectation that within-host evolution should lead to higher viral loads over the long duration of the asymptomatic phase (Read and Taylor, 2001). "
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ABSTRACT: The asymptomatic phase of HIV-1 infections is characterised by a stable set-point viral load (SPVL) within patients. The SPVL is a strong predictor of disease progression and shows considerable variation of multiple orders of magnitude between patients. Recent studies have found that the SPVL in donor and recipient pairs is strongly correlated indicating that the virus genotype strongly influences viral load. Viral genetic factors that increase both viral load and the replicative capacity of the virus would result in rapid within-host evolution to higher viral loads. Reconciling a stable SPVL over time with high SPVL heritability requires viral genetic factors that strongly influence SPVL but only weakly influence the competitive ability of the virus within hosts. We propose a virus trait that affects the activation of target cells, and therefore viral load, but does not confer a competitive advantage to the virus. We incorporate this virus-induced target cell activation into within- and between-host models and determine its effect on the competitive ability of virus strains and on the variation in SPVL in the host population. On the within-host level, our results show that higher rates of virus-induced target cell activation increase the SPVL and confer no selective advantage to the virus. This leads to a build up of diversity in target cell activation rates in the virus population during within-host evolution. On the between-host level, higher rates of target cell activation and therefore higher SPVL affect the transmission potential of the virus. Random selection of a new founder strain from the diverse virus population within a donor results in a standing variation in SPVL in the host population. Therefore, virus-induced target cell activation can explain the heritability of SPVL, the absence of evolution to higher viral loads during infection and a large standing variation in SPVL between hosts.
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