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dc.contributor.authorAllison L. Agwuen_US
dc.contributor.authorMeredith G. Warshawen_US
dc.contributor.authorElizabeth J. McFarlanden_US
dc.contributor.authorGeorge K. Siberryen_US
dc.contributor.authorAnn J. Melvinen_US
dc.contributor.authorAndrew A. Wizniaen_US
dc.contributor.authorLee Fairlieen_US
dc.contributor.authorSandra Boyden_US
dc.contributor.authorPaul Hardingen_US
dc.contributor.authorHans M.L. Spiegelen_US
dc.contributor.authorElaine J. Abramsen_US
dc.contributor.authorVincent J. Careyen_US
dc.contributor.authorMurli Purswanien_US
dc.contributor.authorLinda Aurpibulen_US
dc.contributor.authorVirat Sirisanthanaen_US
dc.contributor.authorChintana Khamrongen_US
dc.contributor.authorJoan Wilsonen_US
dc.contributor.authorMargaret Donnellyen_US
dc.contributor.authorJohn Swetnamen_US
dc.contributor.authorErica Stankievichen_US
dc.contributor.authorSilvina A. Ivaloen_US
dc.contributor.authorIrene Foradorien_US
dc.contributor.authorIvete Martins Gomesen_US
dc.contributor.authorJose Henrique Pilottoen_US
dc.contributor.authorCintia Lopes Da Silvaen_US
dc.contributor.authorMarinella Della Negraen_US
dc.contributor.authorYu Ching Lianen_US
dc.contributor.authorDenise Peluso Pacolaen_US
dc.contributor.authorThuy C. Andersonen_US
dc.contributor.authorTodd C. Nolettoen_US
dc.description.abstractIntroduction: Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a "bridging strategy" to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. Materials & methods: Participants with documented nonadherence, M184V mutation, CD4+T cell count ≥100 cells/mm3and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. Results: Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14-20), 472 cells/mm3(IQR 384-651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2-4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. Conclusions: Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleDecline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trialen_US
article.title.sourcetitlePLoS ONEen_US
article.volume12en_US Johns Hopkins School of Medicineen_US for Biostatistics in AIDS Researchen_US of Colorado School of Medicineen_US Institute of Child Health and Human Developmenten_US's Hospital and Regional Medical Centeren_US Medical Centeren_US of Witwatersranden_US Jude Children's Research Hospitalen_US Institute of Allergy and Infectious Diseasesen_US University, College of Physicians and Surgeonsen_US Hospitalsen_US Mai Universityen_US National Health Systemen_US General de Agudos Carlos G. Duranden_US Geral De Nova Igaucuen_US de Infectologia Emilio Ribasen_US Hopkins Universityen_US University School of Medicineen_US
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