Abstract

In this paper, we review serological and molecular based methods to identify HIV infection recency. The accurate identification of recent HIV infection continues to be an important research area and has implications for HIV prevention and treatment interventions. Longitudinal cohorts that follow HIV negative individuals over time are the current gold standard approach, but they are logistically challenging, time consuming and an expensive enterprise. Methods that utilize cross-sectional testing and biomarker information have become an affordable alternative to the longitudinal approach. These methods use well-characterized biological makers to differentiate between recent and established HIV infections. However, recent results have identified a number of limitations in serological based assays that are sensitive to the variability in immune responses modulated by HIV subtypes, viral load and antiretroviral therapy. Molecular methods that explore the dynamics between the timing of infection and viral evolution are now emerging as a promising approach. The combination of serological and molecular methods may provide a good solution to identify recent HIV infection in cross-sectional data. As part of this review, we present the advantages and limitations of serological and molecular based methods and their potential complementary role for the identification of HIV infection recency.

Highlights

  • Identification of HIV infection recency is crucial for the accurate estimation of HIV incidence, the monitoring of HIV spread [1,2,3], the understanding of HIV transmission dynamics [4,5,6,7] and the evaluation of prevention strategies [8]

  • Implementing single genome amplification and next generation sequencing (NGS) will be of further value in terms of addressing specific research questions related to viral linkage, sexual networks and the identification of sub-epidemics

  • HIV infection recency can be estimated by a set of contemporary serological and molecular methods based using cross-sectional sampling

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Summary

Introduction

Identification of HIV infection recency is crucial for the accurate estimation of HIV incidence, the monitoring of HIV spread [1,2,3], the understanding of HIV transmission dynamics [4,5,6,7] and the evaluation of prevention strategies [8]. The current “gold-standard” approach to identify the recency of infection involves the longitudinal follow-up and repeated testing of uninfected individuals [9,10,11]. Implementation of this approach is logistically challenging, time consuming and expensive [8]. Methods that utilize cross-sectional testing have become an affordable alternative to the longitudinal cohort approach [12] These methods rely on previously characterized biomarkers of recent Vinirufseecs t2i0o15n, 7[,1p3ag–e1–p5a]g.e Serology assays like Calypte Incidence Assay (BED) and Limiting Antigen Assay (LAg) classify recent infections based on markers of the host immune response to HIV, such as antibody leMveetlhs,odasvitdhiatty,uistiolitzyepceroasnsd-sepcrtioopnoalrttieosntin[1g3–h1av6e]. EIA: Enzyme immunoassay test for anti-HIV antibodies; WB: Western Blot. 2

Serological Tests of Recent HIV Infection
Proportion of HIV-1 Specific IgG Antibodies
Antibody Avidity Assays
Anti-p24 IgG3
Inno-LIA HIV Adaptation
Limitations
Molecular Tests of Recent HIV Infection
High Resolution Melting Assay
Sequence Ambiguities as a Marker of Recent HIV Infection
Naïve Bayes Classifiers
Hamming Distances
Sequence Clustering Based Diversity Measure
Multi-Assay Algorithms
Findings
Discussion
Conclusions
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