Interpreting HIV diagnostic histories into infection time estimates: analytical framework and online tool.

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.

Effects of antiretroviral therapy in HIV-positive adults on new HIV infections among young women: a systematic review protocol.

BACKGROUND: The HIV/AIDS pandemic has struck regions, countries, and populations in different ways. With the introduction of antiretroviral drugs, people living with HIV (PLHIV) have a much better prognosis, even though there are still many new infections in young women. The role of widespread antiretroviral therapy (ART) on the incidence of HIV in young women is unknown. METHODS: We will conduct a comprehensive search of MEDLINE (PubMed), Excerpta Medica database (EMBASE), Scopus, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization's (WHO's) library database, Latin American and Caribbean Health Sciences Literature (LILACS), conference abstracts, and gray literature sources to identify any relevant literature. We will include randomized and non-randomized clinical trials and cohort studies in which ART was offered to adults aged 18 and above reporting outcomes in females aged 15 to 24 years. The outcomes of interest are HIV incidence, ART initiation, adherence, retention, and viral load suppression. We will screen titles, abstracts, and the full texts of relevant articles in duplicate. Disagreements will be resolved by consensus. We will extract data on the risk of HIV infection in younger females after the use of ART in the adult population. DISCUSSION: To our knowledge, this is the first systematic review to look at the impact of ART use among adults on HIV incidence in young women. The results of this review will be used in a modeling study to simulate the effects of using ART as an effective tool to prevent sexual transmission of HIV to young women. Our findings will inform the treatment-as-prevention (TasP) strategy to reduce new HIV infections among young women. SYSTEMATIC REVIEW REGISTRATION: The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018099174 .