ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019
Impact of Next-generation Sequencing Defined Human Immunodeficiency Virus Pretreatment Drug Resistance on Virological Outcomes in the ANRS 12249 Treatment-as-Prevention Trial.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01509508 (A Cluster Randomised Trial Comparing the Impact of Immediate Versus South African Recommendations Guided ART Initiation on HIV Incidence. The ARNS 12249 TasP), which is not on this map. Cited by 34 papers, 3 of them syntheses that pooled it.
What it found
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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.
A Cluster Randomised Trial Comparing the Impact of Immediate Versus South African Recommendations Guided ART Initiation on HIV Incidence. The ARNS 12249 TasP (Treatment as Prevention) Trial in Hlabisa Sub-district, KwaZulu-Natal, South Africa.
Who cites it
34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Pooled it
- Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis.The Journal of infectious diseases · 2021Pooled it
- Low-Abundance Drug-Resistant HIV-1 Variants in Antiretroviral Drug-Naive Individuals: A Systematic Review of Detection Methods, Prevalence, and Clinical Impact.The Journal of infectious diseases · 2020Pooled it
- Trial
- Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase.Nature communications · 2020Trial
- Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial.The lancet. HIV · 2020Trial
- The utility of integrating nanopore sequencing into routine HIV-1 drug resistance surveillance.Microbial genomics · 2025Review
- Genetic Diversity and Antiretroviral Resistance in HIV-1-Infected Patients Newly Diagnosed in Cabo Verde.Viruses · 2024Article
- Review
- HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST).BMJ open · 2024Article
- Impact of Human Immunodeficiency Virus Drug Resistance Mutations Detected in Women Prior to Antiretroviral Therapy With Efavirenz + Tenofovir Disoproxil Fumarate + Lamivudine (or Emtricitabine).Open forum infectious diseases · 2024Article
- Performance of the Applied Biosystems HIV-1 Genotyping Kit with Integrase.Journal of clinical microbiology · 2024Article
- Article
- Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients.Clinical case reports · 2022Article
- Evaluating whole HIV-1 genome sequence for estimation of incidence and migration in a rural South African community.Wellcome open research · 2022Article
- Economic, social and demographic impacts of drought on treatment adherence among people living with HIV in rural South Africa: A qualitative analysis.Climate risk management · 2022Article
- Application of Next Generation Sequencing for Diagnosis and Clinical Management of Drug-Resistant Tuberculosis: Updates on Recent Developments in the Field.Frontiers in microbiology · 2022Review
- Optimised electronic patient records to improve clinical monitoring of HIV-positive patients in rural South Africa (MONART trial): study protocol for a cluster-randomised trial.BMC infectious diseases · 2021Article
- Next generation sequencing based in-house HIV genotyping method: validation report.AIDS research and therapy · 2021Article
- Impact of pre-existing drug resistance on risk of virological failure in South Africa.The Journal of antimicrobial chemotherapy · 2021Article
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundPrevious studies in human immunodeficiency virus (HIV)-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS; <50 copies/mL) in individuals prescribed primarily tenofovir/emtricitabine/efavirenz in rural KwaZulu-Natal within a treatment-as-prevention trial.
methodsAmong 1557 HIV-positive individuals who reported no prior ART at study entry and provided plasma samples, 1328 individuals with entry viral load (VL) >1000 copies/mL had next-generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1148 individuals, and the presence of PDR was assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least 1 follow-up VL after ART initiation.
resultsPDR prevalence was 9.5% (109/1148) and 12.8% (147/1148) at 20% and 5% thresholds, respectively. After a median of 1.36 years (interquartile range, 0.91-2.13), mostly on fixed-dose combination tenofovir/emtricitabine/efavirenz, presence of both nonnucleoside reverse transcriptase inhibitor (NNRTI)/nucleoside reverse transcriptase inhibitor PDR vs no PDR was associated with longer time to VS (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.12-0.86), while there was no difference between those with only NNRTI PDR vs no PDR (aHR, 1.05; 95% CI, 0.82-1.34) at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance.
conclusionsNGS uncovered a high prevalence of PDR among participants enrolled in trial clinics in rural KwaZulu-Natal. Dual-class PDR to a mainly tenofovir/emtricitabine/efavirenz regimen was associated with poorer VS. However, there was no impact of NNRTI PDR alone. CLINICAL TRIALS TEGISTRATION: NCT01509508; South African National Clinical Trials Register: DOH-27-0512-3974.
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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 OpenQuestion graph.