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Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring.
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- Author(s): Villa, Giovanni; Ruggiero, Alessandra; Beloukas, Apostolos; Geretti, Anna Maria; Phillips, Richard O; Smith, Colette; Stockdale, Alexander J; Appiah, Lambert T; Sarfo, Fred S; Chadwick, David
- Source:
Journal of Antimicrobial Chemotherapy (JAC); Nov2018, Vol. 73 Issue 11, p3148-3157, 10p- Subject Terms:
DRUG resistance; TENOFOVIR; BISOPROLOL; DRUG monitoring; COMPARATIVE studies; DRUG resistance in microorganisms; HETEROCYCLIC compounds; HIV; HIV infections; RESEARCH methodology; MEDICAL cooperation; GENETIC mutation; RESEARCH; RESEARCH funding; TIME; VIRAL load; EVALUATION research; HIGHLY active antiretroviral therapy; TREATMENT effectiveness; VIREMIA; LAMIVUDINE; ANTI-HIV agents; REVERSE transcriptase inhibitors - Source:
- Additional Information
- Subject Terms:
- Abstract:
Objectives: The resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care.Methods: We studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI. Using deep sequencing, resistance-associated mutations (RAMs) were detected in stored samples collected at tenofovir introduction (T0) and after a median of 4.0 years (T1).Results: At T0, 19/87 (21.8%) subjects showed a detectable viral load and 8/87 (9.2%) had one or more major NNRTI RAMs, whereas 82/87 (94.3%) retained full tenofovir susceptibility. At T1, 79/87 (90.8%) subjects remained on NNRTI-based ART, 5/87 (5.7%) had introduced lopinavir/ritonavir due to immunological failure, and 3/87 (3.4%) had interrupted ART. Whilst 68/87 (78.2%) subjects maintained or achieved virological suppression between T0 and T1, a detectable viral load with NNRTI RAMs at T0 predicted lack of virological suppression at T1. Each treatment interruption, usually reflecting unavailability of the dispensary, doubled the risk of T1 viraemia. Tenofovir, lamivudine and efavirenz selected for K65R, K70E/T, L74I/V and Y115F, alongside M184V and multiple NNRTI RAMs; this resistance profile was accompanied by high viral loads and low CD4 cell counts.Conclusions: Viraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission. [ABSTRACT FROM AUTHOR] - Abstract: Copyright of Journal of Antimicrobial Chemotherapy (JAC) is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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