Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa

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dc.contributor.authorSingh, Y.
dc.contributor.authorCastillo-Mancilla, J.
dc.contributor.authorMadimabe, R.
dc.contributor.authorJennings, L.
dc.contributor.authorFerraris, C. M.
dc.contributor.authorRobbins, R. N.
dc.contributor.authorAnderson, P. L.
dc.contributor.authorRemien, R. H.
dc.contributor.authorOrrell, C.
dc.date.accessioned2023-09-20T09:33:02Z
dc.date.available2023-09-20T09:33:02Z
dc.date.issued2023-09-14
dc.date.updated2023-09-17T03:09:41Z
dc.description.abstractBackground Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA. Methods Adult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome. Results Of 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227–661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150–247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch; EA 33.3 [16–38]%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H). Conclusion TFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance.
dc.identifier.apacitationSingh, Y., Castillo-Mancilla, J., Madimabe, R., Jennings, L., Ferraris, C. M., Robbins, R. N., ... Orrell, C. (2023). Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa. <i>AIDS Research and Therapy</i>, 20(1), 67. http://hdl.handle.net/11427/38792en_ZA
dc.identifier.chicagocitationSingh, Y., J. Castillo-Mancilla, R. Madimabe, L. Jennings, C. M. Ferraris, R. N. Robbins, P. L. Anderson, R. H. Remien, and C. Orrell "Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa." <i>AIDS Research and Therapy</i> 20, 1. (2023): 67. http://hdl.handle.net/11427/38792en_ZA
dc.identifier.citationSingh, Y., Castillo-Mancilla, J., Madimabe, R., Jennings, L., Ferraris, C. M., Robbins, R. N., Anderson, P. L. & Remien, R. H. et al. 2023. Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa. <i>AIDS Research and Therapy.</i> 20(1):67. http://hdl.handle.net/11427/38792en_ZA
dc.identifier.ris TY - Journal Article AU - Singh, Y. AU - Castillo-Mancilla, J. AU - Madimabe, R. AU - Jennings, L. AU - Ferraris, C. M. AU - Robbins, R. N. AU - Anderson, P. L. AU - Remien, R. H. AU - Orrell, C. AB - Background Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA. Methods Adult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome. Results Of 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227–661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150–247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch; EA 33.3 [16–38]%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H). Conclusion TFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance. DA - 2023-09-14 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - AIDS Research and Therapy KW - South Africa KW - HIV resistance KW - Adherence KW - Dried blood spots KW - Tenofovir diphosphate LK - https://open.uct.ac.za PY - 2023 T1 - Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa TI - Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa UR - http://hdl.handle.net/11427/38792 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12981-023-00552-w
dc.identifier.urihttp://hdl.handle.net/11427/38792
dc.identifier.vancouvercitationSingh Y, Castillo-Mancilla J, Madimabe R, Jennings L, Ferraris C M, Robbins R N, et al. Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa. AIDS Research and Therapy. 2023;20(1):67. http://hdl.handle.net/11427/38792.en_ZA
dc.language.rfc3066en
dc.publisherBioMed Central
dc.publisher.departmentMedicine
dc.publisher.facultyHealth SciencesH
dc.rights.holderBioMed Central Ltd., part of Springer Nature
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceAIDS Research and Therapy
dc.source.journalissue1
dc.source.journalvolume20
dc.source.pagination67
dc.source.urihttps://aidsrestherapy.biomedcentral.com/
dc.subjectSouth Africa
dc.subjectHIV resistance
dc.subjectAdherence
dc.subjectDried blood spots
dc.subjectTenofovir diphosphate
dc.titleTenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa
dc.typeJournal Article
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