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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

May 15, 2020

Herbert A Mbunkah, Silvia Bertagnolio, Raph L Hamers, Gillian Hunt, Seth Inzaule, Tobias F Rinke De Wit, Roger Paredes, Neil T Parkin, Michael R Jordan, Karin J Metzner, WHO HIVResNet Working Group

The Journal of Infectious Diseases, Volume 221, Issue 10, 15 May 2020, Pages 1584–1597

PMID: 31809534 | PMCID: PMC7184901 (available on ) | DOI: 10.1093/infdis/jiz650



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.

Source: https://academic.oup.com/jid/article-abstract/221/10/1584/5664819?redirectedFrom=fulltext