Browsing by Author "Welte, Alex"

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    Open Access
    Interpreting HIV diagnostic histories into infection time estimates: analytical framework and online tool
    (2019-10-26) Grebe, Eduard; Facente, Shelley N; Bingham, Jeremy; Pilcher, Christopher D; Powrie, Andrew; Gerber, Jarryd; Priede, Gareth; Chibawara, Trust; Busch, Michael P; Murphy, Gary; Kassanjee, Reshma; Welte, Alex
    Abstract Background It is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the ‘Fiebig staging’ system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results using tests of different sensitivity. To develop a new, more nuanced infection dating algorithm, we generalised the Fiebig approach to accommodate positive and negative diagnostic results generated on the same or different dates, and arbitrary current or future tests – as long as the test sensitivity is known. For this purpose, test sensitivity is the probability of a positive result as a function of time since infection. Methods The present work outlines the analytical framework for infection date estimation using subject-level diagnostic testing histories, and data on test sensitivity. We introduce a publicly-available online HIV infection dating tool that implements this estimation method, bringing together 1) curatorship of HIV test performance data, and 2) infection date estimation functionality, to calculate plausible intervals within which infection likely became detectable for each individual. The midpoints of these intervals are interpreted as infection time ‘point estimates’ and referred to as Estimated Dates of Detectable Infection (EDDIs). The tool is designed for easy bulk processing of information (as may be appropriate for research studies) but can also be used for individual patients (such as in clinical practice). Results In many settings, including most research studies, detailed diagnostic testing data are routinely recorded, and can provide reasonably precise estimates of the timing of HIV infection. We present a simple logic to the interpretation of diagnostic testing histories into infection time estimates, either as a point estimate (EDDI) or an interval (earliest plausible to latest plausible dates of detectable infection), along with a publicly-accessible online tool that supports wide application of this logic. Conclusions This tool, available at https://tools.incidence-estimation.org/idt/ , is readily updatable as test technology evolves, given the simple architecture of the system and its nature as an open source project.
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    Open Access
    Treatment as prevention: preparing the way
    (BioMed Central Ltd, 2011) Williams, Brian; Wood, Robin; Dukay, Victor; Delva, Wim; Ginsburg, David; Hargrove, John; Stander, Martinus; Sheneberger, Robert; Montaner, Julio; Welte, Alex
    Potent antiretroviral therapy (ART) reduces mortality and morbidity in people living with HIV by reducing viral load and allowing their immune systems to recover. The reduction in viral load soon after starting ART has led to the hypothesis that early and widespread ART could prevent onward transmission and therefore eliminate the HIV epidemic in the long term. While several authors have argued that it is feasible to use HIV treatment as prevention (TasP), provided treatment is started sufficiently early, others have reasonably drawn attention to the many operational difficulties that will need to be overcome if the strategy is to succeed in reducing HIV transmission. Furthermore, international public health policy must be based on more than theoretical studies, no matter how appealing. Community randomized controlled trials provide the gold standard for testing the extent to which early treatment reduces incidence, but much still needs to be understood and the immediate need is for operational studies to explore the practical feasibility of this approach. Here, we examine some of the issues to be addressed, the obstacles to be overcome, and strategies that may be necessary if TasP is to be effective. Studies of this kind will provide valuable information for the design of large-scale trials, as well as essential information that will be needed if early treatment is to be incorporated into public health policy.