Late HIV diagnosis: Where we stand and the way forward

Despite years of efforts to improve and simplify access to HIV diagnostics across a variety of key affected populations, late diagnosis remains a burning issue in the WHO European region. Depending on region, cohort and country, 30–60% of people living with HIV/AIDS (PLWH) in Europe enter care late, with hardly any significant improvement in these numbers over the last decade, except perhaps for men who have sex with men (MSM), where the introduction of pre-exposure prophylaxis has helped to increase rates of HIV testing overall, leading to earlier HIV diagnosis [1, 2]. Populations who are particularly affected by late diagnosis across multiple studies include heterosexuals, women and migrants, especially of African descent, and people who use drugs [3, 4]. Delay in HIV diagnosis and related late entry into medical care with clinical and immunological features of severe immunodeficiency are firmly associated with increased frequency of AIDS-defining opportunistic infections and malignancies, 10to 13.6-fold higher mortality risk within 6 months from presentation and reduced life expectancy [5, 6]. Late HIV diagnosis also notably reduces the benefit of reduced transmission risk related to early antiretroviral treatment initiation, while risk of comorbidities in PLWH associated with persistent inflammation remains higher and is often associated with a blunted immunological recovery. Within the current special issue themed ‘Late diagnosis in HIV’, a diverse range of topics around late diagnosis are covered, including updated epidemiology, risk factors for late diagnosis, revised definition of late diagnosis, impact of the COVID19 pandemic, integration of phylogenetic models as well as novel testing approaches and a community perspective on late diagnosis. The concept of late HIV diagnosis evolved from the original consensus definition on late presentation and advanced HIV disease published in 2010 [7]. This definition had the aim to harmonizing data collection throughout Europe on late diagnosis and allowing cross-study or cross-country comparisons, improved surveillance and temporal trend analyses. The obtained consensus defined ‘late presentation’ as entering care with either a CD4 count < 350 cells/μL or an AIDS-defining event, regardless of the CD4 count, while ‘advanced HIV disease’ was defined as care entry with a CD4 count < 200 cells/μL or with an AIDS-defining event, regardless of the CD4 cell count [7]. This definition was widely adopted and, indeed, a plethora of clinical analyses on late presentation have been published subsequently. However, it became clear over time that certain aspects of the definition required further refinement. With the scale up of testing worldwide, identification of individuals with acute retroviral infection associated with a transient decrease in CD4 counts, and therefore possibly misclassified as late-diagnosed individuals, was becoming more common. Moreover, the new definition also uses new wording, as ‘late presentation’ has been associated with stigma within the community, whereas late diagnosis appears to be a more accurate technical term. This special issue features the revised definition developed under the EuroTest initiative in collaboration with ECDC, the WHO Regional Office for Europe and the European AIDS Clinical Society (EACS) [8]. The definition of late HIV diagnosis retained the CD4 count threshold of < 350 cells/μL and an AIDS-defining event, regardless of the CD4 cell count; however, reclassification into the ‘not late’ category is allowed based on the hierarchy of evidence of the recent infection (based on either laboratory markers, negative HIV test with the previous 12 months or symptoms of acute HIV illness) [8]. Exclusion of recent infections from populationlevel analyses allowed researchers to correct the total number of late-diagnosed cases to obtain more precise data. Such reclassification was successfully applied in the study by Kirwan et al., and allowed the calculated late diagnosis rate to be decreased by the overall factor of 14% [9]. The correction rates accounting for recent infection were highest among extensively tested populations (e.g. in MSM aged 15–24 years, the correction factor reached 46%), but were notably lower among populations known to be tested less frequently, such as heterosexually infected and/or older individuals. Novel approaches for implementation of molecular data for validation of risk factors and timelines associated with late diagnosis and advanced HIV disease are also included in this issue. Determination of the number of late-diagnosed cases using the standard definition from 2010 supplemented with phylogenetically inferred time interval between HIV infection and diagnosis provides a Received: 20 October 2022 Accepted: 21 October 2022