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Response to Therapy in Antiretroviral Therapy–Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor–Associated Transmitted Drug Resistance
BACKGROUND: Nonnucleoside reverse transcriptase inhibitor (NNRTI)–associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance. METHODS: We reviewed treatment outcomes in a cohort of HIV-1–...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
JAIDS Journal of Acquired Immune Deficiency Syndromes
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866916/ https://www.ncbi.nlm.nih.gov/pubmed/26855248 http://dx.doi.org/10.1097/QAI.0000000000000942 |
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author | Clutter, Dana S. Fessel, W. Jeffrey Rhee, Soo-Yon Hurley, Leo B. Klein, Daniel B. Ioannidis, John P. A. Silverberg, Michael J. Shafer, Robert W. |
author_facet | Clutter, Dana S. Fessel, W. Jeffrey Rhee, Soo-Yon Hurley, Leo B. Klein, Daniel B. Ioannidis, John P. A. Silverberg, Michael J. Shafer, Robert W. |
author_sort | Clutter, Dana S. |
collection | PubMed |
description | BACKGROUND: Nonnucleoside reverse transcriptase inhibitor (NNRTI)–associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance. METHODS: We reviewed treatment outcomes in a cohort of HIV-1–infected patients with isolated NNRTI TDR who initiated ART between April 2002 and May 2014. In an as-treated analysis, virological failure (VF) was defined as not reaching undetectable virus levels within 24 weeks, virological rebound, or switching regimens during viremia. In an intention-to-treat analysis, failure was defined more broadly as VF, loss to follow-up, and switching during virological suppression. RESULTS: Of 3245 patients, 131 (4.0%) had isolated NNRTI TDR; 122 received a standard regimen comprising 2 NRTIs plus a boosted protease inhibitor (bPI; n = 54), an integrase strand transfer inhibitor (INSTI; n = 52), or an NNRTI (n = 16). The median follow-up was 100 weeks. In the as-treated analysis, VF occurred in 15% (n = 8), 2% (n = 1), and 25% (n = 4) of patients in the bPI, INSTI, and NNRTI groups, respectively. In multivariate regression, there was a trend toward a lower risk of VF with INSTIs than with bPIs (hazard ratio: 0.14; 95% confidence interval: 0.02 to 1.1; P = 0.07). In intention-to-treat multivariate regression, INSTIs had a lower risk of failure than bPIs (hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.82; P = 0.01). CONCLUSIONS: Patients with isolated NNRTI TDR experienced low VF rates with INSTIs and bPIs. INSTIs were noninferior to bPIs in an analysis of VF but superior to bPIs when frequency of switching and loss to follow-up were also considered. |
format | Online Article Text |
id | pubmed-4866916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | JAIDS Journal of Acquired Immune Deficiency Syndromes |
record_format | MEDLINE/PubMed |
spelling | pubmed-48669162016-08-26 Response to Therapy in Antiretroviral Therapy–Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor–Associated Transmitted Drug Resistance Clutter, Dana S. Fessel, W. Jeffrey Rhee, Soo-Yon Hurley, Leo B. Klein, Daniel B. Ioannidis, John P. A. Silverberg, Michael J. Shafer, Robert W. J Acquir Immune Defic Syndr Clinical Science BACKGROUND: Nonnucleoside reverse transcriptase inhibitor (NNRTI)–associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance. METHODS: We reviewed treatment outcomes in a cohort of HIV-1–infected patients with isolated NNRTI TDR who initiated ART between April 2002 and May 2014. In an as-treated analysis, virological failure (VF) was defined as not reaching undetectable virus levels within 24 weeks, virological rebound, or switching regimens during viremia. In an intention-to-treat analysis, failure was defined more broadly as VF, loss to follow-up, and switching during virological suppression. RESULTS: Of 3245 patients, 131 (4.0%) had isolated NNRTI TDR; 122 received a standard regimen comprising 2 NRTIs plus a boosted protease inhibitor (bPI; n = 54), an integrase strand transfer inhibitor (INSTI; n = 52), or an NNRTI (n = 16). The median follow-up was 100 weeks. In the as-treated analysis, VF occurred in 15% (n = 8), 2% (n = 1), and 25% (n = 4) of patients in the bPI, INSTI, and NNRTI groups, respectively. In multivariate regression, there was a trend toward a lower risk of VF with INSTIs than with bPIs (hazard ratio: 0.14; 95% confidence interval: 0.02 to 1.1; P = 0.07). In intention-to-treat multivariate regression, INSTIs had a lower risk of failure than bPIs (hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.82; P = 0.01). CONCLUSIONS: Patients with isolated NNRTI TDR experienced low VF rates with INSTIs and bPIs. INSTIs were noninferior to bPIs in an analysis of VF but superior to bPIs when frequency of switching and loss to follow-up were also considered. JAIDS Journal of Acquired Immune Deficiency Syndromes 2016-06-01 2016-05-16 /pmc/articles/PMC4866916/ /pubmed/26855248 http://dx.doi.org/10.1097/QAI.0000000000000942 Text en Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. |
spellingShingle | Clinical Science Clutter, Dana S. Fessel, W. Jeffrey Rhee, Soo-Yon Hurley, Leo B. Klein, Daniel B. Ioannidis, John P. A. Silverberg, Michael J. Shafer, Robert W. Response to Therapy in Antiretroviral Therapy–Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor–Associated Transmitted Drug Resistance |
title | Response to Therapy in Antiretroviral Therapy–Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor–Associated Transmitted Drug Resistance |
title_full | Response to Therapy in Antiretroviral Therapy–Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor–Associated Transmitted Drug Resistance |
title_fullStr | Response to Therapy in Antiretroviral Therapy–Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor–Associated Transmitted Drug Resistance |
title_full_unstemmed | Response to Therapy in Antiretroviral Therapy–Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor–Associated Transmitted Drug Resistance |
title_short | Response to Therapy in Antiretroviral Therapy–Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor–Associated Transmitted Drug Resistance |
title_sort | response to therapy in antiretroviral therapy–naive patients with isolated nonnucleoside reverse transcriptase inhibitor–associated transmitted drug resistance |
topic | Clinical Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866916/ https://www.ncbi.nlm.nih.gov/pubmed/26855248 http://dx.doi.org/10.1097/QAI.0000000000000942 |
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