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dc.contributor.authorGeretti, AM
dc.contributor.authorFox, Z
dc.contributor.authorJohnson, JA
dc.contributor.authorBooth, C
dc.contributor.authorLipscomb, J
dc.contributor.authorStuyver, LJ
dc.contributor.authorTachedjian, G
dc.contributor.authorBaxter, J
dc.contributor.authorTouloumi, G
dc.contributor.authorLehmann, C
dc.contributor.authorOwen, A
dc.contributor.authorPhillips, A
dc.date.accessioned2021-02-04T02:26:00Z
dc.date.available2021-02-04T02:26:00Z
dc.date.issued2013-07-18
dc.identifierpii: PONE-D-13-11224
dc.identifier.citationGeretti, A. M., Fox, Z., Johnson, J. A., Booth, C., Lipscomb, J., Stuyver, L. J., Tachedjian, G., Baxter, J., Touloumi, G., Lehmann, C., Owen, A. & Phillips, A. (2013). Sensitive Assessment of the Virologic Outcomes of Stopping and Restarting Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy. PLOS ONE, 8 (7), https://doi.org/10.1371/journal.pone.0069266.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/259678
dc.description.abstractBACKGROUND: Non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants have been shown to emerge after interruption of suppressive NNRTI-based antiretroviral therapy (ART) using routine testing. The aim of this study was to quantify the risk of resistance by sensitive testing and correlate the detection of resistance with NNRTI concentrations after treatment interruption and virologic responses after treatment resumption. METHODS: Resistance-associated mutations (RAMs) and NNRTI concentrations were studied in plasma from 132 patients who interrupted suppressive ART within SMART. RAMs were detected by Sanger sequencing, allele-specific PCR, and ultra-deep sequencing. NNRTI concentrations were measured by sensitive high-performance liquid chromatography. RESULTS: Four weeks after NNRTI interruption, 19/31 (61.3%) and 34/39 (87.2%) patients showed measurable nevirapine (>0.25 ng/ml) or efavirenz (>5 ng/ml) concentrations, respectively. Median eight weeks after interruption, 22/131 (16.8%) patients showed ≥1 NNRTI-RAM, including eight patients with NNRTI-RAMs detected only by sensitive testing. The adjusted odds ratio (OR) of NNRTI-RAM detection was 7.62 (95% confidence interval [CI] 1.52, 38.30; p = 0.01) with nevirapine or efavirenz concentrations above vs. below the median measured in the study population. Staggered interruption, whereby nucleos(t)ide reverse transcriptase inhibitors (NRTIs) were continued for median nine days after NNRTI interruption, did not prevent NNRTI-RAMs, but increased detection of NRTI-RAMs (OR 4.25; 95% CI 1.02, 17.77; p = 0.03). After restarting NNRTI-based ART (n = 90), virologic suppression rates <400 copies/ml were 8/13 (61.5%) with NNRTI-RAMs, 7/11 (63.6%) with NRTI-RAMs only, and 51/59 (86.4%) without RAMs. The ORs of re-suppression were 0.18 (95% CI 0.03, 0.89) and 0.17 (95% CI 0.03, 1.15) for patients with NNRTI-RAMs or NRTI-RAMs only respectively vs. those without RAMs (p = 0.04). CONCLUSIONS: Detection of resistant mutants in the rebound viremia after interruption of efavirenz- or nevirapine-based ART affects outcomes once these drugs are restarted. Further studies are needed to determine RAM persistence in untreated patients and impact on newer NNRTIs.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSensitive Assessment of the Virologic Outcomes of Stopping and Restarting Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0069266
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS One
melbourne.source.volume8
melbourne.source.issue7
dc.rights.licenseCC BY
melbourne.elementsid1216467
melbourne.contributor.authorTachedjian, Gilda
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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