PubMed · 2052233
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P J Noble. 1991-06-12. HIV infection.. https://pubmed.ncbi.nlm.nih.gov/2052233/
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BACKGROUND: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. RESULTS: We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. CONCLUSIONS: We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.
BACKGROUND: Preventing HIV infection is still an essential goal in tackling the HIV/AIDS pandemic. Remarkably little is known about how best to reduce HIV incidence because most trials focus on the reduction of risk behaviours and assume an effect on HIV incidence. OBJECTIVE: To discuss the evidence for the effectiveness of HIV prevention strategies, exploring the different types of evidence available: individual and community randomised controlled trials, and observational studies. RESULTS: Although providing a gold standard for evidence, trials have been limited in their scope and are difficult to interpret and generalize. There have been examples of national level successes in preventing HIV which have been detected in surveillance data and understood through behavioural and modelling studies. These have the advantage of being to scale and indicating effectiveness rather than efficacy. CONCLUSIONS: Although randomised trials are important because of their scientific rigor, it is also important that evidence from observational epidemiology is not overlooked. Only if good quality, consistent data are available can the history of the HIV epidemic be appropriately analysed.
Immunoglobulin molecules have long been used in biomedical research as in vitro tools for identification, purification and functional manipulation of target proteins. The specificity and diversity of immunoglobulins can be exploited to target a wide range of intracellular proteins by expressing them in vivo. Such antibody molecules, which are expressed intracellularly and directed to defined sub-cellular compartments, are termed 'intrabodies'. They represent a new and versatile tool that has the potential to manipulate diverse biological processes. Gene knockout, antisense and small interfering RNA knockdown techniques, are employed to characterize the function of many gene products and to validate these gene products as potential drug targets for novel therapeutics, but they have their limitations. The experimental results to date suggest that intrabodies represent a powerful alternative to modulate protein function and analyze its effects. Moreover, they can also be utilized to target specific domains of a particular target protein. Even though their clinical application might take a long time, they can play an important role for target identification and validation in functional genomics and/or proteomics. Here we review the latest advances in the concept, construction and applications of Intrabodies.