Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
pmc-release:
01
06
2024
medline:
5
5
2023
pubmed:
18
3
2023
entrez:
17
3
2023
Statut:
ppublish
Résumé
We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART). We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa. Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen. Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% ( n = 243/283). Of those with TFV detected on the POC assay, 91% ( n = 204/224) had HIVDR, vs. only 66% ( n = 39/59) among those with no TFV detected ( P- value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively. In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.
Identifiants
pubmed: 36928169
doi: 10.1097/QAD.0000000000003520
pii: 00002030-202306010-00011
pmc: PMC10164085
mid: NIHMS1874425
doi:
Substances chimiques
Tenofovir
99YXE507IL
Anti-HIV Agents
0
Anti-Retroviral Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1109-1113Subventions
Organisme : NIAID NIH HHS
ID : P30 AI050409
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124718
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143340
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH122286
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI145537
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI060354
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Références
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Available at: https://clinicalinfo.hiv.gov/sites/default/files/inline-files/AdultandAdolescentGL.pdf [Accessed 5 October 2020].
World Health Organization. Updated recommendations on HIV prevention, infant diagnosis, antiretroviral initiation and monitoring. 2021. Available at: https://www.who.int/publications-detail-redirect/9789240022232 [Accessed 25 March 2021].
Castillo-Mancilla JR, Haberer JE. Adherence measurements in HIV: new advancements in pharmacologic methods and real-time monitoring . Curr HIV/AIDS Rep 2018; 15:49–59.
Spinelli MA, Haberer JE, Chai PR, Castillo-Mancilla J, Anderson PL, Gandhi M. Approaches to objectively measure antiretroviral medication adherence and drive adherence interventions . Curr HIV/AIDS Rep 2020; 17:301–314.
Gandhi M, Bacchetti P, Spinelli MA, Okochi H, Baeten JM, Siriprakaisil O, et al. Validation of a urine tenofovir immunoassay for adherence monitoring to PrEP and ART and establishing the cutoff for a point-of-care test . J Acquir Immune Defic Syndr 2019; 81:72–77.
Gandhi M, Wang G, King R, Rodrigues WC, Vincent M, Glidden DV, et al. Development and validation of the first point-of-care assay to objectively monitor adherence to HIV treatment and prevention in real-time in routine settings . AIDS 2020; 34:255–260.
Pratt GW, Fan A, Melakeberhan B, Klapperich CM. A competitive lateral flow assay for the detection of tenofovir . Anal Chim Acta 2018; 1017:34–40.
Sevenler D, Niu X, Dossantos S, Toner M, Cressey TR, Sandlin RD, et al. Point-of-care semi-quantitative test for adherence to tenofovir alafenamide or tenofovir disoproxil fumarate . J Antimicrob Chemother 2022; 77:996–999.
Spinelli MA, Rodrigues WC, Wang G, Vincent M, Glidden DV, Okochi H, et al. High accuracy of a real-time urine antibody-based tenofovir point-of-care test compared with laboratory-based ELISA in diverse populations . J Acquir Immune Defic Syndr 2020; 84:149–152.
Siedner MJ, Bwana MB, Moosa MS, Paul M, Pillay S, McCluskey S, et al. The REVAMP trial to evaluate HIV resistance testing in sub-Saharan Africa: a case study in clinical trial design in resource limited settings to optimize effectiveness and cost effectiveness estimates . HIV Clin Trials 2017; 18:149–155.
Siedner MJ, Moosa M-YS, McCluskey S, Gilbert RF, Pillay S, Aturinda I, et al. Resistance testing for management of HIV virologic failure in sub-Saharan Africa: an unblinded randomized controlled trial . Ann Intern Med 2021; 174:1683–1692.
Liu TF, Shafer RW. Web resources for HIV type 1 genotypic-resistance test interpretation . Clin Infect Dis 2006; 42:1608–1618.
Collier DA, Monit C, Gupta RK. The impact of HIV-1 drug escape on the global treatment landscape . Cell Host Microbe 2019; 26:48–60.
Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, noninferiority SAILING study . Lancet 2013; 382:700–708.
Musinguzi N, Muganzi CD, Boum Y, Ronald A, Marzinke MA, Hendrix CW, et al. Comparison of subjective and objective adherence measures for preexposure prophylaxis against HIV infection among serodiscordant couples in East Africa . AIDS 2016; 30:1121–1129.
Arnsten JH, Demas PA, Farzadegan H, Grant RW, Gourevitch MN, Chang CJ, et al. Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: comparison of self-report and electronic monitoring . Clin Infect Dis 2001; 33:1417–1423.
Jennings L, Kellermann T, Spinelli M, Nkantsu Z, Cogill D, van Schalkwyk M, et al. Drug resistance, rather than low tenofovir levels in blood or urine, is associated with tenofovir emtricitabine, and efavirenz failure in resource-limited settings . AIDS Res Hum Retroviruses 2022; 38:455–462.
Hermans LE, Steegen K, Ter Heine R, Schuurman R, Tempelman HA, Moraba R, et al. Drug level testing as a strategy to determine eligibility for drug resistance testing after failure of ART: a retrospective analysis of South African adult patients on second-line ART . J Int AIDS Soc 2020; 23:e25501.
Castillo-Mancilla JR, Edwards JA, Brijkumar J, Moosa M-Y, Zhao Y, Ofotokun I, et al. Tenofovir diphosphate levels in dried blood spots are associated with virologic failure and resistance to first-line therapy in South Africa: a case-control cohort study . J Int AIDS Soc 2021; 24:e25849.
van Zyl G, Jennings L, Kellermann T, Nkantsu Z, Cogill D, van Schalkwyk M, et al. Urine tenofovir-monitoring predicts HIV viremia in patients treated with high genetic-barrier regimens . AIDS 2022; 36:2057–2062.
Podsadecki TJ, Vrijens BC, Tousset EP, Rode RA, Hanna GJ. White coat compliance limits the reliability of therapeutic drug monitoring in HIV-1-infected patients . HIV Clin Trials 2008; 9:238–246.