TY - JOUR
T1 - Low-Abundance Drug-Resistant HIV-1 Variants in Antiretroviral Drug-Naive Individuals
T2 - A systematic review of detection methods, prevalence, and clinical impact
AU - Mbunkah, Herbert A.
AU - Bertagnolio, Silvia
AU - Hamers, Raph L.
AU - Hunt, Gillian
AU - Inzaule, Seth
AU - Rinke de Wit, Tobias F.
AU - Paredes, Roger
AU - Parkin, Neil T.
AU - Jordan, Michael R.
AU - Metzner, Karin J.
N1 - Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/27
Y1 - 2020/4/27
N2 - Background: The presence of high-abundance drug-resistant HIV-1 jeopardizes success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) at levels <15%-25% of the virus population in antiretroviral (ARV) drug-naive individuals remains controversial. Methods: We systematically reviewed 103 studies assessing prevalence, detection methods, technical and clinical detection cutoffs, and clinical significance of LA-DRVs in antiretroviral drug-naive adults. Results: In total, 14 919 ARV drug-naive individuals were included. Prevalence of LA-DRVs (ie, proportion of individuals harboring LA-DRVs) was 0%-100%. Technical detection cutoffs showed a 4 log range (0.001%-10%); 42/103 (40.8%) studies investigating the impact of LA-DRVs on ART; 25 studies included only individuals on first-line nonnucleoside reverse transcriptase inhibitor-based ART regimens. Eleven of those 25 studies (44.0%) reported a significantly association between preexisting LA-DRVs and risk of virological failure whereas 14/25 (56.0%) did not. Conclusions: Comparability of the 103 studies is hampered by high heterogeneity of the studies' designs and use of different methods to detect LA-DRVs. Thus, evaluating clinical impact of LA-DRVs on first-line ART remains challenging. We, the WHO HIVResNet working group, defined central areas of future investigations to guide further efforts to implement ultrasensitive resistance testing in routine settings.
AB - Background: The presence of high-abundance drug-resistant HIV-1 jeopardizes success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) at levels <15%-25% of the virus population in antiretroviral (ARV) drug-naive individuals remains controversial. Methods: We systematically reviewed 103 studies assessing prevalence, detection methods, technical and clinical detection cutoffs, and clinical significance of LA-DRVs in antiretroviral drug-naive adults. Results: In total, 14 919 ARV drug-naive individuals were included. Prevalence of LA-DRVs (ie, proportion of individuals harboring LA-DRVs) was 0%-100%. Technical detection cutoffs showed a 4 log range (0.001%-10%); 42/103 (40.8%) studies investigating the impact of LA-DRVs on ART; 25 studies included only individuals on first-line nonnucleoside reverse transcriptase inhibitor-based ART regimens. Eleven of those 25 studies (44.0%) reported a significantly association between preexisting LA-DRVs and risk of virological failure whereas 14/25 (56.0%) did not. Conclusions: Comparability of the 103 studies is hampered by high heterogeneity of the studies' designs and use of different methods to detect LA-DRVs. Thus, evaluating clinical impact of LA-DRVs on first-line ART remains challenging. We, the WHO HIVResNet working group, defined central areas of future investigations to guide further efforts to implement ultrasensitive resistance testing in routine settings.
KW - HIV-1
KW - HIV-1 drug resistance
KW - antiretroviral therapy
KW - antitretroviral drug-naive individuals
KW - low-abundance drug-resistant HIV-1 variants
KW - minority variants
KW - next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=85085710912&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/infdis/jiz650
DO - https://doi.org/10.1093/infdis/jiz650
M3 - Review article
C2 - 31809534
SN - 0022-1899
VL - 221
SP - 1584
EP - 1597
JO - Journal of infectious diseases
JF - Journal of infectious diseases
IS - 10
ER -