Moving towards a reliable HIV incidence test - current status, resources available, future directions and challenges ahead

Abstract

In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.

Keywords: HIV/AIDS; incidence.

Fig. 1.

Impact of mean duration of recent infection and false recency ratio on sample size requirements to detect reductions in incidence. This figure demonstrates the sample size required to detect a 40% reduction in incidence for the country of Botswana (power 0·8, alpha 0·05, design effect 1·3). Calculations come from https://finddx.shinyapps.io/Sample_size_calculator/.

Fig. 2.

CEPHIA incidence assay critical path. Listed on the right are specific milestones that should be demonstrated before an assay moves forward to further development.

Fig. 3.

Clade/geographical breakdown of CEPHIA repository specimens.