Re-assessing the late HIV diagnosis surveillance definition in the era of increased and frequent testing.

Objectives: Late HIV diagnosis (CD4 <350 cells/mm ) is a key public health metric. In an era of more frequent testing, the likelihood of HIV diagnosis occurring during seroconversion, when CD4 counts may dip below 350, is greater. We applied a correction, considering markers of recent infection, and re-assessed 1-year mortality following late diagnosis.

PrEP use and unmet PrEP-need among men who have sex with men in London prior to the implementation of a national PrEP programme, a cross-sectional study from June to August 2019.

Background: Access to prevention options, including HIV pre-exposure prophylaxis (PrEP), remains a public health priority for gay, bisexual, and other men who have sex with men (MSM), especially in London. We describe PrEP use in a London community sample of MSM before the introduction of a national PrEP programme in October 2020.

Methods: From June-August 2019, MSM aged ≥ 18 recruited from London commercial venues were asked to self-complete a sexual health questionnaire and provide an oral fluid sample for anonymous HIV antibody testing.

Ecosystem design as an avenue for improving services provided by carbonate producing marine ecosystems.

Ecosystem Design (ED) is an approach for constructing habitats that places human needs for ecosystem services at the center of intervention, with the overarching goal of establishing self-sustaining habitats which require limited management. This concept was originally developed for use in mangrove ecosystems, and is understandably controversial, as it markedly diverges from other protection approaches that assign human use a minor priority or exclude it. However, the advantage of ED lies within the considered implementation of these designed ecosystems, thus preserving human benefits from potential later disturbances.

Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance.

Background: Precise and cost-efficient human immunodeficiency virus (HIV) incidence and drug resistance surveillances are in high demand for the advancement of the 90-90-90 "treatment for all" target.

Methods: We developed microdrop HIV sequencing for the HIV incidence and drug resistance assay (HIDA), a single-blood-draw surveillance tool for incidence and drug resistance mutation (DRM) detection. We amplified full-length HIV envelope and pol gene sequences within microdroplets, and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences.

Surveillance of HIV-1 transmitted integrase strand transfer inhibitor resistance in the UK.

Background: HIV treatment guidelines have traditionally recommended that all HIV-positive individuals are tested for evidence of drug resistance prior to starting ART. Testing for resistance to reverse transcriptase inhibitors and PIs is well established in routine care. However, testing for integrase strand transfer inhibitor (InSTI) resistance is less consistent.

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.

Challenges to the performance of current HIV diagnostic assays and the need for centralized specimen archives: a review of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) repository.

New challenges for diagnosis of HIV infection abound, including the impact on key viral and immunological markers of HIV vaccine studies, pre-exposure prophylaxis usage and breakthrough infections, and very early initiation of anti-retroviral treatment. These challenges impact the performance of current diagnostic assays, and require suitable specimens for development and evaluation. In this article we review and describe an archive developed by the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA), in order to identify the critical features required to create a centralized specimen archive to support these current and future developments.

Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance.

Background: Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance.

Methods: We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens.

Combination prevention and HIV: a cross-sectional community survey of gay and bisexual men in London, October to December 2016.

BackgroundMen who have sex with men (MSM) are at risk of HIV and are an important population to monitor and ameliorate combination prevention efforts.AimTo estimate HIV prevalence and identify factors associated with frequent HIV testing (≥ 2 HIV tests in the last year) and pre-exposure prophylaxis (PrEP) use among MSM in London.MethodsFor this cross-sectional study, MSM recruited from 22 social venues provided oral-fluid samples for anonymous HIV antibody (Ab) testing and completed a questionnaire.

The concordance of the limiting antigen and the Bio-Rad avidity assays in persons from Estonia infected mainly with HIV-1 CRF06_cpx.

Background: Serological assays to determine HIV incidence have contributed to estimates of HIV incidence, monitoring of HIV spread, and evaluation of prevention strategies. Two frequently used incidence assays are the Sedia HIV-1 LAg-Avidity EIA (LAg) and the Bio-Rad avidity incidence (BRAI) assays with a mean duration of recent infection (MDRI) of 130 and 240 days for subtype B infections, respectively. Little is known about how these assays perform with recombinant HIV-1 strains.

HIV Testing and Sexual Health Among Black African Men and Women in London, United Kingdom.

Importance: Black African adults are disproportionately affected by HIV in the United Kingdom. Many within this population acquire HIV after migration or are diagnosed late. Data are needed to inform targeted interventions to increase HIV testing and prevention in this population.

A generalizable method for estimating duration of HIV infections using clinical testing history and HIV test results.

Objective: To determine the precision of new and established methods for estimating duration of HIV infection.

Design: A retrospective analysis of HIV testing results from serial samples in commercially available panels, taking advantage of extensive testing previously conducted on 53 seroconverters.

Methods: We initially investigated four methods for estimating infection timing: method 1, 'Fiebig stages' based on test results from a single specimen; method 2, an updated '4th gen' method similar to Fiebig stages but using antigen/antibody tests in place of the p24 antigen test; method 3, modeling of 'viral ramp-up' dynamics using quantitative HIV-1 viral load data from antibody-negative specimens; and method 4, using detailed clinical testing history to define a plausible interval and best estimate of infection time.

Discrimination between recent and non-recent HIV infections using routine diagnostic serological assays.

The suitability of routine diagnostic HIV assays to accurately discriminate between recent and non-recent HIV infections has not been fully investigated. The aim of this study was to compare an established HIV recency assay, the Sedia limiting antigen HIV avidity assay (LAg), with the diagnostic assays; Abbott ARCHITECT HIV Ag/Ab Combo and INNO-LIA HIV line assays. Samples from all new HIV diagnoses in Ireland from January to December 2016 (n = 455) were tested.

Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction.

Background: Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired human immunodeficiency virus type 1 (HIV-1) can be transmitted, generated de novo through virus replication, or technical errors. The first form is likely to persist and result in treatment failure, while the latter two could be stochastic and transient.

Methods: Ultradeep sequencing of plasma samples from 835 individuals with recent HIV-1 infection in the United Kingdom was performed to detect DRMinVs at a mutation frequency between 2% and 20%.

Short Communication: Dried Blood Spots Stored at Room Temperature Should Not Be Used for HIV Incidence Testing.

The limiting antigen (LAg)-avidity assay is a serologic assay used for cross-sectional HIV incidence testing. We compared the results obtained with the LAg-avidity assay using dried blood spot (DBS) samples stored at room temperature (18°C-25°C) or stored frozen at -80°C with results obtained from matched plasma samples. Matched DBS and plasma samples (306 paired samples) were collected in the HIV Prevention Trials Network (HPTN) 068 trial in South Africa (2012-2014).

HIV incidence among sexual health clinic attendees in England: First estimates for black African heterosexuals using a biomarker, 2009-2013.

Introduction: The HIV epidemic in England is largely concentrated among heterosexuals who are predominately black African and men who have sex with men (MSM). We present for the first time trends in annual HIV incidence for adults attending sexual health clinics, where 80% of all HIV diagnoses are made.

Methods: We identified newly diagnosed incident HIV using a recent infection testing algorithm (RITA) consisting of a biomarker (AxSYM assay, modified to determine antibody avidity), epidemiological and clinical information.

Loss of coral reef growth capacity to track future increases in sea level.

Sea-level rise (SLR) is predicted to elevate water depths above coral reefs and to increase coastal wave exposure as ecological degradation limits vertical reef growth, but projections lack data on interactions between local rates of reef growth and sea level rise. Here we calculate the vertical growth potential of more than 200 tropical western Atlantic and Indian Ocean reefs, and compare these against recent and projected rates of SLR under different Representative Concentration Pathway (RCP) scenarios. Although many reefs retain accretion rates close to recent SLR trends, few will have the capacity to track SLR projections under RCP4.

Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates.

Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening, and next-generation assays.

Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms.

Background: Custom HIV staging assays, including the Sedia HIV-1 Limiting Antigen (LAg) Avidity EIA and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify "recent" infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and long-standing infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications.

Methods: We tested a panel of 2500 well-characterized specimens with estimable duration of HIV infection with the 3 assays and the unmodified ARCHITECT.

A Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Sequences in Kiev: Findings Among Key Populations.

Background: The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission.

Methods: Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013-March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering.

HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral Replication.

Background: Human immunodeficiency virus (HIV) antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals receiving antiretroviral therapy (ART).

Methods: HIV antibody responses were measured over time in the presence or absence of suppressive ART and were compared to the HIV reservoir size and expression of antiviral restriction factors.

Comparison of cross-sectional HIV incidence assay results from dried blood spots and plasma.

Background: Assays have been developed for cross-sectional HIV incidence estimation using plasma samples. Large scale surveillance programs are planned using dried blood spot (DBS) specimens for incidence assessment. However, limited information exists on the performance of HIV cross-sectional incidence assays using DBS.