Evidence mapPaperPMID 37705102Full record

Observational studyAIDS research and therapy2023

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

Y Singh, J Castillo-Mancilla, R Madimabe, L Jennings, C M Ferraris, R N Robbins, P L Anderson, R H Remien, C Orrell

Open access · goldAbstract readObservational Study
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Y SinghDesmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa. Yashna.Singh@hiv-research.org.za.
J Castillo-MancillaUniversity of Colorado, Aurora, CO, USA.
R MadimabeDesmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa.
L JenningsDesmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa.
C M FerrarisNew York State Psychiatric Institute, New York, USA.
R N RobbinsNew York State Psychiatric Institute, New York, USA.
P L AndersonUniversity of Colorado, Aurora, CO, USA.
R H RemienNew York State Psychiatric Institute, New York, USA.
C OrrellDesmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa.
Desmond Tutu HIV Foundation · ZANew York State Psychiatric InstituteUniversity of Colorado Anschutz Medical Campus · USColumbia University Irving Medical Center · USUniversity of Cape Town · ZA

Funding

NIAID NIH HHS R01 AI122300
6 · The paper itself

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.

Indexed as

HIV-1HIV InfectionsHIV SeropositivityAdenineAdultAnti-Retroviral AgentsFemaleHumansMaleOrganophosphatesSouth AfricaAdenineAnti-Retroviral AgentsOrganophosphatestenofovir diphosphateAdherenceDried blood spotsHIV resistanceSouth AfricaTenofovir diphosphate

Identifiers

PMID37705102
PMCPMC10500931
OpenAlexW4386726726

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.