24
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Challenges of HIV diagnosis and management in the context of pre‐exposure prophylaxis (PrEP), post‐exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV‐status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV‐specific antibody point‐of‐care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre‐exposure prophylaxis (PrEP) or post‐exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false‐negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection.

          Discussion

          Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV‐specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource‐limited, high HIV burden settings where HIV‐antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource‐wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified.

          Conclusions

          With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.

          Related collections

          Most cited references45

          • Record: found
          • Abstract: found
          • Article: not found

          The immune response during acute HIV-1 infection: clues for vaccine development

          Key Points The early virological factors in HIV-1 infection, including transmission and the nature of the founder virus, can affect the time course of viraemia through the early peak to set point. The identification of patients within the first few weeks of HIV-1 infection has provided early evidence of immune system damage, including massive apoptosis of CD4+ T cells, which is associated with the presence of apoptotic microparticles and TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) in the blood, and damage to germinal centres in mucosal lymphoid tissues. The first innate immune responses include the appearance of acute-phase proteins, early cytokine storm and activation of natural killer (NK) cells. An innate immune response to HIV-1 can be damaging, however, as it can draw susceptible T cells to the infection foci. The first T cell response controls the founder virus by killing infected T cells. However, the T cell response also selects mutational changes in the founder virus, allowing immune evasion. The first B cell response consists of early immune complexes, followed by non-neutralizing antibodies against the founder virus and then the slow development of broadly acting neutralizing antibodies. Development of vaccines that rapidly induce broadly acting neutralizing antibodies might be beneficial in preventing HIV infection. Understanding the early events and immune responses is crucial to devising vaccine strategies that can improve the weak protection offered by current HIV vaccines that are being trialled, such as the RV144 (Thai) efficacy trial.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection.

            The characterization of primary HIV infection by the analysis of serial plasma samples from newly infected persons using multiple standard viral assays. A retrospective study involving two sets of archived samples from HIV-infected plasma donors. (A) 435 samples from 51 donors detected by anti-HIV enzyme immunoassays donated during 1984-1994; (B) 145 specimens from 44 donors detected by p24 antigen screening donated during 1996-1998. Two US plasma products companies. The timepoints of appearance of HIV-1 markers and viral load concentrations during primary HIV infection. The pattern of sequential emergence of viral markers in the 'A' panels was highly consistent, allowing the definition and estimation of the duration of six sequential stages. From the 'B' panels, the viral load at p24 antigen seroconversion was estimated by regression analysis at 10 000 copies/ml (95% CI 2000-93 000) and the HIV replication rate at 0.35 log copies/ml/day, corresponding to a doubling time in the preseroconversion phase of 20.5 h (95% CI 18.2-23.4 h). Consequently, an RNA test with 50 copies/ml sensitivity would detect HIV infection approximately 7 days before a p24 antigen test, and 12 days before a sensitive anti-HIV test. The sequential emergence of assay reactivity allows the classification of primary HIV-1 infection into distinct laboratory stages, which may facilitate the diagnosis of recent infection and stratification of patients enrolled in clinical trials. Quantitative analysis of preseroconversion replication rates of HIV is useful for projecting the yield and predictive value of assays targeting primary HIV infection.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection

              Antiretroviral therapy (ART) during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical treatment interruption (ATI). We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following ATI, indicating that additional strategies are required to control or eradicate HIV.
                Bookmark

                Author and article information

                Contributors
                s.fidler@imperial.ac.uk
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                18 December 2019
                December 2019
                : 22
                : 12 ( doiID: 10.1002/jia2.v22.12 )
                : e25419
                Affiliations
                [ 1 ] Imperial College London London United Kingdom
                [ 2 ] Imperial College Healthcare NHS Trust London United Kingdom
                [ 3 ] Kenya Medical Research Institute‐Wellcome Trust Research Programme Kilifi Kenya
                [ 4 ] Nuffield Department of Medicine University of Oxford Oxford United Kingdom
                [ 5 ] Department of HIV and Global Hepatitis Programme WHO Geneva Switzerland
                [ 6 ] Africa Health Research Institute Durban South Africa
                [ 7 ] HIV Pathogenesis Programme Doris Duke Medical Research Institute University of KwaZulu‐Natal Durban South Africa
                [ 8 ] The Ragon Institute of Massachusetts General Hospital Massachusetts Institute of Technology and Harvard University Cambridge MA USA
                [ 9 ] Max Planck Institute for Infection Biology Berlin Germany
                [ 10 ] Department of Internal Medicine Division of Infectious Diseases UNC School of Medicine University of North Carolina At Chapel Hill Chapel Hill NC USA
                [ 11 ] Division of Global HIV and TB Centers for Disease Control and Prevention Atlanta GA USA
                [ 12 ] NAM Aidsmap London United Kingdom
                [ 13 ] PrEP in Europe Initiative London United Kingdom
                [ 14 ] U.S. Military HIV Research Program Walter Reed Army Institute of Research Silver Spring MD USA
                [ 15 ] Henry M. Jackson Foundation for the Advancement of Military Medicine Bethesda MD USA
                [ 16 ] National Infection Service, Public Health England London United Kingdom
                [ 17 ] Department of Infection Royal Free London NHS Foundation Trust London United Kingdom
                [ 18 ] Imperial College NIHR BRC London United Kingdom
                Author notes
                [*] [* ] Corresponding author: Sarah Fidler, Faculty of Medicine, Imperial College London, Jefferiss Research Trust Laboratories, 2nd Floor, Medical School Building, St Mary's Campus, Norfolk Place, Paddington, London W2 1PG, United Kingdom. Tel +44 (0)20 7594 3910/+44 7912 205671. ( s.fidler@ 123456imperial.ac.uk )

                Author information
                https://orcid.org/0000-0001-8232-9413
                https://orcid.org/0000-0001-5917-9664
                https://orcid.org/0000-0003-1369-3224
                https://orcid.org/0000-0003-1676-7583
                Article
                JIA225419
                10.1002/jia2.25419
                6918508
                31850686
                f55b5ec5-4f55-41b1-b225-a26b2e47358c
                © 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 June 2019
                : 22 October 2019
                Page count
                Figures: 0, Tables: 0, Pages: 6, Words: 6997
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                December 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.3 mode:remove_FC converted:18.12.2019

                Infectious disease & Microbiology
                acute hiv infection,pre‐exposure prophylaxis,post‐exposure prophylaxis,immediate antiretroviral therapy,hiv testing algorithms,indeterminate hiv test

                Comments

                Comment on this article