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Low-abundance drug-resistant HIV-1 variants in antiretroviral drug-naïve individuals: A systematic review of detection methods, prevalence, and clinical impact


Mbunkah, Herbert A; Bertagnolio, Silvia; Hamers, Raph L; Hunt, Gillian; Inzaule, Seth; Rinke de Wit, Tobias F; Paredes, Roger; Parkin, Neil T; Jordan, Michael R; Metzner, Karin J (2020). Low-abundance drug-resistant HIV-1 variants in antiretroviral drug-naïve individuals: A systematic review of detection methods, prevalence, and clinical impact. Journal of Infectious Diseases, 221(10):1584-1597.

Abstract

BACKGROUND

The presence of high-abundance drug-resistant HIV-1 jeopardizes the success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) present at levels <15-25% of the virus population in antitretroviral (ARV) drug-naïve individuals remains controversial.

METHODS

We systematically reviewed 103 studies assessing the prevalence, detection methods, technical and clinical detection cut-offs, and the clinical significance of LA-DRVs in antiretroviral drug-naïve adults.

RESULTS

In total, 14,919 ARV drug-naïve individuals were included. The prevalence of LA-DRVs, i.e., the proportion of individuals harboring LA-DRVs, varied between 0 and 100%. Technical detection cut-offs showed a 4 log range (0.001-10%). 42/103 (40.8%) studies investigating the impact of LA-DRVs on ART; 25 studies (67.6%) included only individuals on first-line NNRTI-based ART regimens. Eleven of those 25 studies (44.0%) reported a significantly association between pre-existing LA-DRVs and risk of virological failure whereas 14/25 (66.0%) did not.

CONCLUSIONS

The comparability of the 103 studies is hampered by the high heterogeneity of the studies' designs and the use of different methods to detect LA-DRVs. Thus, evaluating the 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.

Abstract

BACKGROUND

The presence of high-abundance drug-resistant HIV-1 jeopardizes the success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) present at levels <15-25% of the virus population in antitretroviral (ARV) drug-naïve individuals remains controversial.

METHODS

We systematically reviewed 103 studies assessing the prevalence, detection methods, technical and clinical detection cut-offs, and the clinical significance of LA-DRVs in antiretroviral drug-naïve adults.

RESULTS

In total, 14,919 ARV drug-naïve individuals were included. The prevalence of LA-DRVs, i.e., the proportion of individuals harboring LA-DRVs, varied between 0 and 100%. Technical detection cut-offs showed a 4 log range (0.001-10%). 42/103 (40.8%) studies investigating the impact of LA-DRVs on ART; 25 studies (67.6%) included only individuals on first-line NNRTI-based ART regimens. Eleven of those 25 studies (44.0%) reported a significantly association between pre-existing LA-DRVs and risk of virological failure whereas 14/25 (66.0%) did not.

CONCLUSIONS

The comparability of the 103 studies is hampered by the high heterogeneity of the studies' designs and the use of different methods to detect LA-DRVs. Thus, evaluating the 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.

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Additional indexing

Contributors:HIVResNet working group
Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:27 April 2020
Deposited On:06 Feb 2020 08:13
Last Modified:29 Jul 2020 13:25
Publisher:Oxford University Press
ISSN:0022-1899
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/infdis/jiz650
PubMed ID:31809534

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