Extensive drug resistance during low-level HIV viraemia while taking NNRTI-based ART supports lowering the viral load threshold for regimen switch in resource-limited settings: a pre-planned analysis from the SESOTHO trial

被引:14
作者
Brown, Jennifer Anne [1 ,2 ,3 ]
Amstutz, Alain [1 ,3 ,4 ]
Nsakala, Bienvenu Lengo [5 ]
Seeburg, Ulrike [2 ,3 ]
Vanobberghen, Fiona [1 ,3 ]
Muhairwe, Josephine [5 ]
Klimkait, Thomas [2 ,3 ]
Labhardt, Niklaus Daniel [1 ,3 ,4 ]
机构
[1] Swiss Trop & Publ Hlth Inst, Basel, Switzerland
[2] Univ Basel, Dept Biomed, Mol Virol, Basel, Switzerland
[3] Univ Basel, Basel, Switzerland
[4] Univ Hosp Basel, Dept Infect Dis & Hosp Epidemiol, Basel, Switzerland
[5] SolidarMed, Partnerships Hlth, Maseru, Lesotho
基金
瑞士国家科学基金会;
关键词
ANTIRETROVIRAL THERAPY; VIROLOGICAL FAILURE; MULTICENTER; 2ND-LINE;
D O I
10.1093/jac/dkab025
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objectives: WHO guidelines on ART define the HIV-1 viral load (VL) threshold for treatment failure at 1000 copies/mL. The Switch Either near Suppression Or THOusand (SESOTHO) trial, conducted in Lesotho from 2017 to 2020, found that patients with persistent viraemia below this threshold (100-999 copies/mL) benefit from switching to second-line ART. This pre-planned nested study assesses the prevalence of resistance-associated mutations (RAMs) in SESOTHO trial participants. Methods: The SESOTHO trial [registered at ClinicalTrials.gov (NCT03088241)] enrolled 80 persons taking NNRTI-based first-line ART with low-level HIV-1 viraemia (100-999 copies/mL) and randomized them (1:1) to switch to a PI-based second-line regimen (switch) or continue on first-line therapy (control). We sequenced relevant regions of the viral pol gene using plasma samples obtained at enrolment and 36 weeks. RAMs were classified with the Stanford HIV Drug Resistance Database. Results: Sequencing data were obtained for 37/80 (46%) participants at baseline and 26/48 (54%) participants without viral suppression to <50 copies/mL at 36 weeks (21 control participants and 5 switch participants). At baseline, 31/37 (84%) participants harboured high-level resistance to at least two drugs of their current regimen. At 36 weeks, 17/21 (81%) control participants harboured resistance to at least two drugs of their current regimen, while no PI-associated resistance was detected in the 5 switch participants with ongoing viraemia. Conclusions: Among persons with low-level viraemia while taking NNRTI-based first-line ART enrolled in the SESOTHO trial, the majority harboured HIV-1 with RAMs that necessitate ART modification. These findings support lowering the VL threshold triggering a switch to second-line ART in future WHO guidelines.
引用
收藏
页码:1294 / 1298
页数:5
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