Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 2;35(2):227-234.
doi: 10.1097/QAD.0000000000002740.

High-throughput sequencing reveals a high prevalence of pretreatment HIV-1 drug resistance in Sweden

Emmi Andersson  1   2 , Anoop Ambikan  1 , Johanna Brännström  3   4 , Shambhu G Aralaguppe  1 , Aylin Yilmaz  5 , Jan Albert  2   6 , Ujjwal Neogi  1 , Anders Sönnerborg  1   2   3   7
Affiliations

High-throughput sequencing reveals a high prevalence of pretreatment HIV-1 drug resistance in Sweden

Emmi Andersson et al. AIDS. .

Abstract

Objectives: HIV-1 pretreatment drug resistance (PDR) is a global concern. Our aim was to evaluate high-throughput sequencing (HTS) for HIV-1 resistance testing and describe PDR in Sweden, where 75% of diagnosed individuals are foreign-born.

Design: Cross-sectional study.

Methods: Individuals entering HIV-1 care in Sweden 2017 to March 2019 (n = 400) were included if a viremic sample was available (n = 220). HTS was performed using an in-house assay. Drug resistance mutations (DRMs) (based on Stanford HIV DB vs. 8.7) at levels 1-5%, 5-19% and at least 20% of the viral population were described. Results from HTS and routine Sanger sequencing were compared.

Results: HTS was successful in 88% of patients, 92% when viral load was at least 1000 copies/ml. DRMs at any level in protease and/or reverse transcriptase were detected in 95 individuals (49%), whereas DRMs at least 20% in 35 (18%) individuals. DRMs at least 20% correlated well to findings in routine Sanger sequencing. Protease/reverse transcriptase (PR/RT) DRMs at least 20% were predicted by treatment exposure; adjusted OR 9.28 (95% CI 2.24-38.43; P = 0.002) and origin in Asia; adjusted OR 20.65 (95% CI 1.66-256.24; P = 0.02). Nonnucleoside reverse transcriptase inhibitor (NNRTI) DRMs at least 20% were common (16%) and over-represented in individuals originating from sub-Saharan Africa or Asia. Low-level integrase strand transfer inhibitor (INSTI) DRMs less than 20% were detected in 15 individuals (8%) with no association with INSTI exposure.

Conclusion: Our HTS can efficiently detect PDR and findings of DRMs at least 20% compare well to routine Sanger sequencing. The high prevalence of PDR was because of NNRTI DRMs and associated with migration from areas with emerging PDR.

PubMed Disclaimer

References

    1. Gupta RK, Gregson J, Parkin N, Haile-Selassie H, Tanuri A, Andrade Forero L, et al. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis . Lancet Infect Dis 2018; 18:346–355.
    1. World Health Organization, Switzerland. Update of recommendations on first- and second-line antiretroviral regimens, 2019. Available at: www.who.int/hiv ; [Accessed 4 October 2019].
    1. Telele NF, Kalu AW, Gebre-Selassie S, Fekade D, Marrone G, Grossmann S, et al. A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort . BMC Infect Dis 2019; 19:569.
    1. El Bouzidi K, Kemp SA, Datir RP, Murtala-Ibrahim F, Aliyu A, Kwaghe V, et al. High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment . J Antimicrob Chemother 2020; 75:1575–1579.
    1. McGee KS, Okeke NL, Hurt CB, McKellar MS. Canary in the coal mine? Transmitted mutations conferring resistance to all integrase strand transfer inhibitors in a treatment-naive patient . Open Forum Infect Dis 2018; 5:ofy294.

Publication types

Substances