ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2015
Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00084136 (Randomized, Open-Label Evaluation of Efficacy of Once-Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Persons From Resource-Limited Settings), which is not on this map. Cited by 48 papers, 4 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.
Randomized, Open-Label Evaluation of Efficacy of Once-Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Persons From Resource-Limited Settings (PEARLS) Trial
Who cites it
48 citing papers in PubMed, 4 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- HIV-1 Antiretroviral Drug Resistance in Mozambique: A Systematic Review and Meta-Analysis.Viruses · 2024Pooled it
- 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
- HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis.The Lancet. Infectious diseases · 2018Pooled 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
- High rates of transmitted NNRTI resistance among persons with acute HIV infection in Malawi: implications for first-line dolutegravir scale-up.AIDS research and therapy · 2019Trial
- Virologic outcomes in early antiretroviral treatment: HPTN 052.HIV clinical trials · 2017Trial
- Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.Journal of acquired immune deficiency syndromes (1999) · 2016Trial
- Treatment of Advanced HIV in the Modern Era.Drugs · 2025Review
- Evaluating the Efficacy of Repurposed Antiretrovirals in Hepatitis B Virus Treatment: A Narrative Review of the Pros and Cons.International journal of molecular sciences · 2025Review
- Genotypic Diversity and Pre-Treatment Resistance Characteristic Analysis Among Newly Diagnosed HIV-1-Positive MSM from 2020-2022 in Jiaxing City, China.Current HIV research · 2025Article
- HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST).BMJ open · 2024Article
- The Burden of Pretreatment HIV Drug Resistance in Trinidad and Tobago.AIDS research and human retroviruses · 2024Article
- Pre-existing low-frequency resistance mutations increase the risk of antiretroviral treatment failure in HIV-1 naïve patients.Chinese medical journal · 2023Article
- Genetic Diversity and Characteristics of Drug Resistance Among Treatment-Naive People Living with HIV in Xi'an, China.Drug design, development and therapy · 2023Article
- Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations.Pathogens (Basel, Switzerland) · 2022Article
- A Phase IV Study on Safety, Tolerability and Efficacy of Dolutegravir, Lamivudine, and Tenofovir Disoproxil Fumarate in Treatment Naïve Adult Indian Patients Living with HIV-1.Pragmatic and observational research · 2022Article
- 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
28 authors at 19 institutions in 8 countries.
Funding
Abstract
backgroundEvaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites.
methodsPol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance-failure association.
resultsIn the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex-treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04-2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22-.98).
conclusionsIn this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. CLINICAL TRIALS REGISTRATION: NCT00084136.
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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.