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Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort.
AIDS. 2020 07 15; 34(9):1331-1338.AIDS

Abstract

OBJECTIVE

Pretreatment HIV-drug resistance (PDR, HIVDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is increasing globally. NNRTIs continue to be used as first-line antiretroviral therapy (ART) in some communities due to the cost of dolutegravir-based ART or dolutegravir-associated adverse events. A simplified version of the oligonucleotide ligation assay (OLA) - 'OLA-Simple' - is a low-cost, near point-of-care assay that provides ready-to-use lyophilized reagents and reports HIVDR mutations as colored lines on lateral flow strips. Our objective was to design and validate OLA-Simple for a Mexican cohort.

DESIGN

OLA-Simple probes to detect K65R, K103N/S, Y181C, M184V, and G190A were optimized for HIV Mexican sequences. Sixty clinical plasma specimens were analyzed by OLA-Simple by technicians blinded to Illumina-MiSeq sequences, and HIVDR results were compared.

METHODS

Plasma RNA was tested using OLA-Simple kits. OLA-Simple lateral flow strips were read by in-house software, and were classified as mutant or wild-type at each codon. The comparison of results by OLA-Simple and Miseq was used to generate receiver-operating characteristic curves.

RESULTS

OLA-Simple PCR amplified 59 of 60 specimens and successfully genotyped 287 of 295 codons, with eight of 295 (2.7%) indeterminate results. Compared to MiSeq, OLA-Simple gave five of 295 (1.7%) false-positive and four of 295 (1.4%) false-negative results. Excluding indeterminate results, OLA-Simple classified mutant with an accuracy of 97.4 and 98.8% when using thresholds at 10 and 25% mutant within an individual's HIV quasispecies, respectively.

CONCLUSIONS

Compared to MiSeq, OLA-Simple detected HIVDR with high sensitivity and accuracy. OLA-Simple could expand access to affordable and rapid HIVDR testing to guide appropriate ART choices in populations using NNRTI-based ART.

Authors+Show Affiliations

Department of Bioengineering. Global Health of Women, Adolescents, and Children (Global WACh), School of Public Health, University of Washington.Center for Global Infectious Disease Research, Seattle Children's Research Institute.Department of Bioengineering. Paul G. Allen Center for Computer Science & Engineering, University of Washington, Seattle, Washington, USA.Centre for Research in Infectious Diseases of the National Institute of Respiratory Diseases (CIENI/INER), Mexico City, Mexico.Centre for Research in Infectious Diseases of the National Institute of Respiratory Diseases (CIENI/INER), Mexico City, Mexico.Centre for Research in Infectious Diseases of the National Institute of Respiratory Diseases (CIENI/INER), Mexico City, Mexico.Centre for Research in Infectious Diseases of the National Institute of Respiratory Diseases (CIENI/INER), Mexico City, Mexico.Centre for Research in Infectious Diseases of the National Institute of Respiratory Diseases (CIENI/INER), Mexico City, Mexico.Centre for Research in Infectious Diseases of the National Institute of Respiratory Diseases (CIENI/INER), Mexico City, Mexico.Centre for Research in Infectious Diseases of the National Institute of Respiratory Diseases (CIENI/INER), Mexico City, Mexico.Centre for Research in Infectious Diseases of the National Institute of Respiratory Diseases (CIENI/INER), Mexico City, Mexico.Department of Bioengineering.Center for Global Infectious Disease Research, Seattle Children's Research Institute. Departments of Global Health, Medicine, Pediatrics, and Laboratory Medicine, University of Washington, Seattle, Washington, Washington, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32205723

Citation

Panpradist, Nuttada, et al. "Near Point-of-care, Point-mutation Test to Detect Drug Resistance in HIV-1: a Validation Study in a Mexican Cohort." AIDS (London, England), vol. 34, no. 9, 2020, pp. 1331-1338.
Panpradist N, Beck IA, Ruth PS, et al. Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. AIDS. 2020;34(9):1331-1338.
Panpradist, N., Beck, I. A., Ruth, P. S., Ávila-Ríos, S., García-Morales, C., Soto-Nava, M., Tapia-Trejo, D., Matías-Florentino, M., Paz-Juarez, H. E., Del Arenal-Sanchez, S., Reyes-Terán, G., Lutz, B. R., & Frenkel, L. M. (2020). Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. AIDS (London, England), 34(9), 1331-1338. https://doi.org/10.1097/QAD.0000000000002524
Panpradist N, et al. Near Point-of-care, Point-mutation Test to Detect Drug Resistance in HIV-1: a Validation Study in a Mexican Cohort. AIDS. 2020 07 15;34(9):1331-1338. PubMed PMID: 32205723.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. AU - Panpradist,Nuttada, AU - Beck,Ingrid A, AU - Ruth,Parker S, AU - Ávila-Ríos,Santiago, AU - García-Morales,Claudia, AU - Soto-Nava,Maribel, AU - Tapia-Trejo,Daniela, AU - Matías-Florentino,Margarita, AU - Paz-Juarez,Hector E, AU - Del Arenal-Sanchez,Silvia, AU - Reyes-Terán,Gustavo, AU - Lutz,Barry R, AU - Frenkel,Lisa M, PY - 2020/3/25/pubmed PY - 2020/3/25/medline PY - 2020/3/25/entrez SP - 1331 EP - 1338 JF - AIDS (London, England) JO - AIDS VL - 34 IS - 9 N2 - OBJECTIVE: Pretreatment HIV-drug resistance (PDR, HIVDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is increasing globally. NNRTIs continue to be used as first-line antiretroviral therapy (ART) in some communities due to the cost of dolutegravir-based ART or dolutegravir-associated adverse events. A simplified version of the oligonucleotide ligation assay (OLA) - 'OLA-Simple' - is a low-cost, near point-of-care assay that provides ready-to-use lyophilized reagents and reports HIVDR mutations as colored lines on lateral flow strips. Our objective was to design and validate OLA-Simple for a Mexican cohort. DESIGN: OLA-Simple probes to detect K65R, K103N/S, Y181C, M184V, and G190A were optimized for HIV Mexican sequences. Sixty clinical plasma specimens were analyzed by OLA-Simple by technicians blinded to Illumina-MiSeq sequences, and HIVDR results were compared. METHODS: Plasma RNA was tested using OLA-Simple kits. OLA-Simple lateral flow strips were read by in-house software, and were classified as mutant or wild-type at each codon. The comparison of results by OLA-Simple and Miseq was used to generate receiver-operating characteristic curves. RESULTS: OLA-Simple PCR amplified 59 of 60 specimens and successfully genotyped 287 of 295 codons, with eight of 295 (2.7%) indeterminate results. Compared to MiSeq, OLA-Simple gave five of 295 (1.7%) false-positive and four of 295 (1.4%) false-negative results. Excluding indeterminate results, OLA-Simple classified mutant with an accuracy of 97.4 and 98.8% when using thresholds at 10 and 25% mutant within an individual's HIV quasispecies, respectively. CONCLUSIONS: Compared to MiSeq, OLA-Simple detected HIVDR with high sensitivity and accuracy. OLA-Simple could expand access to affordable and rapid HIVDR testing to guide appropriate ART choices in populations using NNRTI-based ART. SN - 1473-5571 UR - https://www.unboundmedicine.com/medline/citation/32205723/Near_point_of_care_point_mutation_test_to_detect_drug_resistance_in_HIV_1:_a_validation_study_in_a_Mexican_cohort_ L2 - https://doi.org/10.1097/QAD.0000000000002524 DB - PRIME DP - Unbound Medicine ER -