Drug resistance outcomes of long-term ART with tenofovir disoproxil.pdf (363.49 kB)
Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring
journal contribution
posted on 2023-06-09, 20:04 authored by Giovanni Villa, Richard O Phillips, Colette Smith, Alexander J Stockdale, Alessandra Ruggiero, Apostolos Beloukas, Lambert T Appiah, David Chadwick, Fred S Sarfo, Anna Maria GerettiObjectives: 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.
History
Publication status
- Published
File Version
- Published version
Journal
Journal of Antimicrobial ChemotherapyISSN
0305-7453Publisher
Oxford University PressExternal DOI
Issue
11Volume
73Page range
3148-3157Department affiliated with
- BSMS Publications
Research groups affiliated with
- Brighton and Sussex Centre for Global Health Research Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2020-01-03First Open Access (FOA) Date
2020-01-03First Compliant Deposit (FCD) Date
2020-01-02Usage metrics
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