Evidence map›Paper›PMID 40782815›Full record

ArticleThe lancet. HIV2025

The clinical and economic impact of genotypic resistance testing for people diagnosed with persistent virological non-suppression on tenofovir-lamivudine-dolutegravir in South Africa: a modelling study.

Emily P Hyle, Linda-Gail Bekker, Suzanne M McCluskey, Wanyi Chen, Paul E Sax, Mahomed-Yunus Moosa, Munashe Machoko, Audrey Bangs, Kim Steegen, Mark J Siedner and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The lancet. HIV, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Trial
  2. 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

20 authors.

Emily P HyleDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: ehyle@mgh.harvard.edu.
Linda-Gail BekkerDesmond Tutu HIV Center, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Suzanne M McCluskeyDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; University of KwaZulu-Natal, Durban, South Africa.
Wanyi ChenMedical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.
Paul E SaxHarvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Mahomed-Yunus MoosaDepartment of Infectious Diseases, University of KwaZulu-Natal, Durban, South Africa.
Munashe MachokoMedical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.
Audrey BangsMedical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.
Kim SteegenNational Priority Programme, National Health Laboratory Service, Johannesburg, South Africa; Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
Mark J SiednerDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; University of KwaZulu-Natal, Durban, South Africa; Africa Health Research Institute, KwaZulu-Natal, South Africa.
David A M C van de VijverDepartment of Viroscience, Erasmus University Rotterdam, Rotterdam, Netherlands.
Stephen C ReschCenter for Health Decision Science, Harvard T H Chan School of Public Health, Boston, MA, USA.
Anne M NeilanDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of General Academic Pediatrics, Massachusetts General Hospital, Boston, MA, USA.
Andrew PhillipsEpidemiology and Biostatistics, University College London, London, UK.
Rochelle P WalenskyHarvard Kennedy School, Cambridge, MA, USA; American Academy of Berlin, Berlin, Germany.
Richard J LessellsKwaZulu-Natal Research and Innovation Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa.
Milton C WeinsteinCenter for Health Decision Science, Harvard T H Chan School of Public Health, Boston, MA, USA.
Caitlin M DugdaleDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Robin WoodDesmond Tutu HIV Center, University of Cape Town, Cape Town, South Africa.
Kenneth A FreedbergDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.

Funding

Adolescent-tailored HIV treatment and prevention strategies in South Africa: projecting clinical benefits and valueR01HD111355 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$1.1M
A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure for Individuals on TLD in Sub-Saharan AfricaR01AI167699 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$665k
Virologic and pharmacologic determinants of dolutegravir failure in East AfricaK23AI143470 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Suzanne McCluskey · 2021 to 2023
$631k
NIAID NIH HHS K23 AI143470NIAID NIH HHS R01 AI167699NIAID NIH HHS R37 AI058736NICHD NIH HHS K08 HD101342NICHD NIH HHS R01 HD111355Wellcome Trust
6 · The paper itself

Abstract

backgroundPersistent virological non-suppression among people with HIV receiving tenofovir-lamivudine-dolutegravir (TLD) can result from poor adherence with or without resistance; however, genotypic resistance testing (GRT) is not recommended routinely in South Africa. We examined the clinical and economic effect of GRT for all South African adults diagnosed with persistent virological non-suppression on TLD.

methodsIn this modelling study, we used the previously validated Cost-Effectiveness of Preventing AIDS Complications-International microsimulation model to compare three strategies: (1) continued TLD (baseline); (2) immediate switch to tenofovir-lamivudine plus ritonavir-boosted darunavir; and (3) GRT prompting switch to tenofovir-lamivudine plus ritonavir-boosted darunavir for people with dolutegravir resistance or TLD continuation for people without dolutegravir resistance. We estimated that 2·3% and 28·5% of the baseline population have dolutegravir resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance, respectively. We also examined the effect of a low-cost, point-of-care urine tenofovir test in development to detect recent antiretroviral therapy use (84% sensitivity and 50% specificity), with GRT only when positive. Costs included GRT (US$157 per test), TLD ($45 per year), tenofovir-lamivudine plus ritonavir-boosted darunavir ($247 per year), and urine tenofovir testing ($2 per test). Outcomes included life-years, costs (provider perspective), and incremental cost-effectiveness ratios (ICERs; $ per disability-adjusted life-year [DALY]). We considered cost-effectiveness thresholds of less than $3310 per DALY (base case) and less than $1100 to $4250 per DALY.

findingsBased on our model, we estimated that continued TLD results in 14·11 undiscounted life-years and costs $5380 discounted at 3%; GRT results in 14·36 life-years and costs $5860 (0·14 discounted DALYs averted; ICER $3500 per DALY). Immediate switch results in fewer DALYs averted and higher costs. GRT has an ICER of $3310 per DALY or less when baseline dolutegravir resistance prevalence is ≥2·5% or genotypic resistance test costs ≤$147 per test. Urine tenofovir testing to identify GRT eligibility results in an ICER of $2300 per DALY; the ICER would be less than $1100 per DALY if urine test specificity is 0·87 or greater and costs $2 per test or test specificity is higher than 0·98 and costs $10 per test or less.

interpretationGRT could increase life expectancy for people with HIV and persistent virological non-suppression on TLD in South Africa and could be cost-effective, especially at lower test costs. At current effectiveness and costs of tenofovir-lamivudine plus ritonavir-boosted darunavir, an immediate switch would not be preferred.

fundingNational Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the MGH Jerome and Celia Reich Endowed Scholar in HIV/AIDS Research Award.

Indexed as

Anti-HIV AgentsDrug Resistance, ViralHeterocyclic Compounds, 3-RingHIV-1HIV InfectionsAdultCost-Benefit AnalysisDolutegravirFemaleGenotypeHumansLamivudineMaleOxazinesPiperazinesPyridonesAnti-HIV AgentsDolutegravirHeterocyclic Compounds, 3-RingLamivudineOxazinesPiperazinesPyridonesTenofovir

Identifiers

PMID40782815
PMCPMC12403227

What Socratic holds

Textmetadata
LicenceTDM
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.