Observational studyAIDS research and therapy2023
Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa.
Observational study in AIDS research and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Trial
- In-utero exposure to tenofovir-containing pre-exposure prophylaxis and bone mineral content in HIV-unexposed infants in South Africa.Journal of the International AIDS Society · 2024Trial
- Predictors of treatment-emergent resistance to dolutegravir.The lancet. HIV · 2025Review
- Tenofovir diphosphate concentrations in dried blood spots predict future HIV suppression but not virologic failure in adolescents with HIV.AIDS (London, England) · 2025Article
- Novel Micro-LC-MS/MS Method for the Quantification of Tenofovir and Its Active Metabolite Tenofovir-Diphosphate in Biological Matrices for Therapeutic Drug Monitoring.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Resistance to Dolutegravir in Treatment-experienced Patients in South Africa: A Retrospective Cohort Study.Journal of acquired immune deficiency syndromes (1999) · 2025Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundSuboptimal 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.
methodsAdult 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.
resultsOf 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).
conclusionTFV-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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.