HIV‐1 testing in the context of expanding PrEP modalities

Abstract Introduction Multiple effective antiretroviral‐based pre‐exposure prophylaxis (PrEP) modalities for HIV‐1 prevention are now available or under investigation but their safe rollout requires implementable HIV‐1 testing strategies that accurately identify rare cases of HIV‐1 acquisition. Curr...

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Main Authors: Urvi M. Parikh, Jana L. Jacobs, Njambi Njuguna, Kristine Torjesen, John W. Mellors
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Journal of the International AIDS Society
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Online Access:https://doi.org/10.1002/jia2.26491
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author Urvi M. Parikh
Jana L. Jacobs
Njambi Njuguna
Kristine Torjesen
John W. Mellors
author_facet Urvi M. Parikh
Jana L. Jacobs
Njambi Njuguna
Kristine Torjesen
John W. Mellors
author_sort Urvi M. Parikh
collection DOAJ
description Abstract Introduction Multiple effective antiretroviral‐based pre‐exposure prophylaxis (PrEP) modalities for HIV‐1 prevention are now available or under investigation but their safe rollout requires implementable HIV‐1 testing strategies that accurately identify rare cases of HIV‐1 acquisition. Current PrEP testing guidelines and testing algorithms in PrEP studies are varied, using single or combinations of rapid antibody‐based diagnostic testing, qualitative or quantitative nucleic acid testing, and/or sample collection for retrospective analyses with sensitive research assays for HIV‐1 nucleic acid detection. The objective of this commentary is to summarize current and alternative HIV testing approaches for PrEP implementation to guide best practices for individual programmes. Discussion Diagnosing HIV‐1 in PrEP users is challenging because (1) rarity of breakthrough HIV‐1 in individuals on PrEP that increases the risk of a false‐positive test; (2) modification of acute HIV infection by PrEP; and (3) PrEP delivery in community settings with inadequate testing infrastructure. Current best practices indicate the use of rapid diagnostic tests or self‐testing as recommended by national testing algorithms and the World Health Organization (WHO). The use of nucleic acid testing such as plasma HIV‐1 RNA polymerase chain reaction may allow earlier detection of HIV‐1 but feasibility and risk of false positive are downsides. Sensitive tests to detect single‐copy HIV‐1 RNA in plasma and integrated proviral DNA in blood mononuclear cells may be important methods to resolve ambiguous HIV‐1 diagnosis in research settings. Delayed diagnoses could lead to drug resistance emergence under long‐acting PrEP selection, whereas single unconfirmed false‐positive tests could create diagnostic challenges in users of long‐acting PrEP. The cost, feasibility and positive predictive value of HIV tests are important considerations for PrEP programmes. Conclusions Optimal strategies to detect HIV‐1 acquisition among users of different PrEP modalities are evolving. While new guidance from the WHO recommends HIV‐1 testing by serological assays or self‐testing with PrEP use, feasible plans for clinical management of rare cases of breakthrough on PrEP and ambiguous diagnoses are still needed. The data from PrEP studies and scale‐up will help us assess the value of different tests and testing approaches for their inclusion in HIV detection algorithms across PrEP modalities.
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spelling doaj-art-5f104f9be10b4eeeb947b2b4b8749cb02025-08-20T03:17:39ZengWileyJournal of the International AIDS Society1758-26522025-07-0128S2n/an/a10.1002/jia2.26491HIV‐1 testing in the context of expanding PrEP modalitiesUrvi M. Parikh0Jana L. Jacobs1Njambi Njuguna2Kristine Torjesen3John W. Mellors4Division of Infectious Diseases Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Infectious Diseases Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USAFHI 360 Kenya Nairobi KenyaFHI 360 Durham North Carolina USADivision of Infectious Diseases Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USAAbstract Introduction Multiple effective antiretroviral‐based pre‐exposure prophylaxis (PrEP) modalities for HIV‐1 prevention are now available or under investigation but their safe rollout requires implementable HIV‐1 testing strategies that accurately identify rare cases of HIV‐1 acquisition. Current PrEP testing guidelines and testing algorithms in PrEP studies are varied, using single or combinations of rapid antibody‐based diagnostic testing, qualitative or quantitative nucleic acid testing, and/or sample collection for retrospective analyses with sensitive research assays for HIV‐1 nucleic acid detection. The objective of this commentary is to summarize current and alternative HIV testing approaches for PrEP implementation to guide best practices for individual programmes. Discussion Diagnosing HIV‐1 in PrEP users is challenging because (1) rarity of breakthrough HIV‐1 in individuals on PrEP that increases the risk of a false‐positive test; (2) modification of acute HIV infection by PrEP; and (3) PrEP delivery in community settings with inadequate testing infrastructure. Current best practices indicate the use of rapid diagnostic tests or self‐testing as recommended by national testing algorithms and the World Health Organization (WHO). The use of nucleic acid testing such as plasma HIV‐1 RNA polymerase chain reaction may allow earlier detection of HIV‐1 but feasibility and risk of false positive are downsides. Sensitive tests to detect single‐copy HIV‐1 RNA in plasma and integrated proviral DNA in blood mononuclear cells may be important methods to resolve ambiguous HIV‐1 diagnosis in research settings. Delayed diagnoses could lead to drug resistance emergence under long‐acting PrEP selection, whereas single unconfirmed false‐positive tests could create diagnostic challenges in users of long‐acting PrEP. The cost, feasibility and positive predictive value of HIV tests are important considerations for PrEP programmes. Conclusions Optimal strategies to detect HIV‐1 acquisition among users of different PrEP modalities are evolving. While new guidance from the WHO recommends HIV‐1 testing by serological assays or self‐testing with PrEP use, feasible plans for clinical management of rare cases of breakthrough on PrEP and ambiguous diagnoses are still needed. The data from PrEP studies and scale‐up will help us assess the value of different tests and testing approaches for their inclusion in HIV detection algorithms across PrEP modalities.https://doi.org/10.1002/jia2.26491HIV preventionHIV‐1 diagnosticsHIV testing algorithmslong‐acting cabotegravirpre‐exposure prophylaxisrapid diagnostic tests
spellingShingle Urvi M. Parikh
Jana L. Jacobs
Njambi Njuguna
Kristine Torjesen
John W. Mellors
HIV‐1 testing in the context of expanding PrEP modalities
Journal of the International AIDS Society
HIV prevention
HIV‐1 diagnostics
HIV testing algorithms
long‐acting cabotegravir
pre‐exposure prophylaxis
rapid diagnostic tests
title HIV‐1 testing in the context of expanding PrEP modalities
title_full HIV‐1 testing in the context of expanding PrEP modalities
title_fullStr HIV‐1 testing in the context of expanding PrEP modalities
title_full_unstemmed HIV‐1 testing in the context of expanding PrEP modalities
title_short HIV‐1 testing in the context of expanding PrEP modalities
title_sort hiv 1 testing in the context of expanding prep modalities
topic HIV prevention
HIV‐1 diagnostics
HIV testing algorithms
long‐acting cabotegravir
pre‐exposure prophylaxis
rapid diagnostic tests
url https://doi.org/10.1002/jia2.26491
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