Use of HIV Recency Assays for HIV Incidence Estimation and Other Surveillance Use Cases: Systematic Review

Abstract

Background HIV assays designed to detect recent infection, also known as “recency assays,” are often used to estimate HIV incidence in a specific country, region, or subpopulation, alone or as part of recent infection testing algorithms (RITAs). Recently, many countries and organizations have become interested in using recency assays within case surveillance systems and routine HIV testing services to measure other indicators beyond incidence, generally referred to as “non-incidence surveillance use cases.” Objective This review aims to identify published evidence that can be used to validate methodological approaches to recency-based incidence estimation and non-incidence use cases. The evidence identified through this review will be used in the forthcoming technical guidance by the World Health Organization (WHO) and United Nations Programme on HIV/AIDS (UNAIDS) on the use of HIV recency assays for identification of epidemic trends, whether for HIV incidence estimation or non-incidence indicators of recency. Methods To identify the best methodological and field implementation practices for the use of recency assays to estimate HIV incidence and trends in recent infections for specific populations or geographic areas, we conducted a systematic review of the literature to (1) understand the use of recency testing for surveillance in programmatic and laboratory settings, (2) review methodologies for implementing recency testing for both incidence estimation and non-incidence use cases, and (3) assess the field performance characteristics of commercially available recency assays. Results Among the 167 documents included in the final review, 91 (54.5%) focused on assay or algorithm performance or methodological descriptions, with high-quality evidence of accurate age- and sex-disaggregated HIV incidence estimation at national or regional levels in general population settings, but not at finer geographic levels for prevention prioritization. The remaining 76 (45.5%) described the field use of incidence assays including field-derived incidence (n=45), non-incidence (n=25), and both incidence and non-incidence use cases (n=6). The field use of incidence assays included integrating RITAs into routine surveillance and assisting with molecular genetic analyses, but evidence was generally weaker or only reported on what was done, without validation data or findings related to effectiveness of using non-incidence indicators calculated through the use of recency assays as a proxy for HIV incidence. Conclusions HIV recency assays have been widely validated for estimating HIV incidence in age- and sex-specific populations at national and subnational regional levels; however, there is a lack of evidence validating the accuracy and effectiveness of using recency assays to identify epidemic trends in non-incidence surveillance use cases. More research is needed to validate the use of recency assays within HIV testing services, to ensure findings can be accurately interpreted to guide prioritization of public health programming.

A systematic review of limiting antigen avidity enzyme immunoassay for detection of recent HIV-1 infection to expand supported applications

“…This review complements the findings of Facente et al 's systematic review of the use of recency assays for HIV incidence estimation. 56 In addition, LAg has the potential to be used in other study designs, such as HIV PrEP clinical trials, where measuring HIV incidence is critical for assessing the efficacy of new prevention modalities. 6 The potential use in HIV PrEP clinical trials could expand the available options of prevention modalities.…”

Recent HIV infections among newly diagnosed individuals living with HIV in rural Lesotho: Secondary data from the VIBRA cluster-randomized trial

“…These figures provide important insights into ongoing transmission patterns in the region. However, they should be viewed critically since there is still a lack of proper field validation of these rapid recency assays [ 28 ] and especially misleading when not combined with VL testing [ 29 ]. More research is needed to validate such assays in the field.…”

Recent HIV Infection: Diagnosis and Public Health Implications

“…Therefore, the detection and measurement of recent infections can serve HIV surveillance by providing a more accurate picture of new transmission events [ 54 ]. Beyond assisting in incidence measurement and serving surveillance purposes, testing for recency could also help public health personnel identify clusters and geographical hotspots of recent HIV transmission, and conduct contact tracing [ 55 , 56 ]. All these pieces of information could be extremely useful for designing and evaluating prevention interventions [ 31 ].…”

“…This initial immaturity includes lower levels/titers of IgG antibodies, reduced avidity of antibodies with antigens, and fewer IgG antibodies specifically against HIV compared to the overall IgG amount [ 31 ]. Specific assays take advantage of the quantitative and qualitative characteristics of the evolution of the antibody response and are able to detect recent infections in the post-seroconversion period [ 55 , 77 ]. The first effort of this kind was based on using sensitive/less sensitive (detuned) enzyme immunoassays (EIA) on specimens that had been collected cross-sectionally [ 58 ].…”

“…In general, the performance of serological assays for detecting recent HIV infection in the post-seroconversion period depends on the HIV infection stage, receipt of antiretrovirals as treatment or prevention, variability associated with HIV subtypes, and individual variability in immune response [ 33 , 55 , 79 ]. In particular, the wrong classification of long-term infections as recent increases in HIV-infected people with low CD4 T-cell counts or in HIV-infected people on antiretrovirals, including those who started ART soon after their infection [ 79 , 88 , 89 , 93 , 99 , 100 , 101 ].…”