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Review
. 2025 Nov 6;81(4):e132-e136.
doi: 10.1093/cid/ciaf161.

Utilizing HIV Proviral DNA to Assess for the Presence of HIV Drug Resistance

Annemarie M Wensing  1   2 , Charlotte Charpentier  3 , Vincent Calvez  4 , Francesca Ceccherini-Silberstein  5 , Huldrych F Günthard  6 , Donna M Jacobsen  7 , Roger Paredes  8   9 , Robert W Shafer  10 , Douglas D Richman  11
Affiliations
Review

Utilizing HIV Proviral DNA to Assess for the Presence of HIV Drug Resistance

Annemarie M Wensing et al. Clin Infect Dis. .

Abstract

The improved efficacy and tolerability of newer antiretroviral drugs, as well as the introduction of long-acting regimens, have prompted more frequent therapy switches in individuals on suppressive antiretroviral therapy (ART). For these individuals, the assessment of HIV drug resistance using DNA from peripheral blood lymphocytes has become increasingly popular. However, compared with HIV RNA-based analyses, implementation of HIV DNA testing as an alternative approach in clinical care requires new documented quality-assessment procedures and clinical validation. Furthermore, the use of HIV DNA to assess drug resistance has some distinct technical and biologic challenges that are relevant to the clinical management of people with HIV. This Viewpoint article addresses the issues relevant to clinical virologists and treating physicians for the interpretation of drug-resistance testing or subtype assessment based on DNA analysis, when HIV RNA genotypic assessment is not possible.

Keywords: HIV-1; antiretroviral drugs; drug resistance; long-acting drug regimen; proviral DNA testing.

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Conflict of interest statement

Potential conflicts of interest. A. M. W.: investigator-initiated grant paid to their institution from Gilead Sciences, Inc; consulting fees from Gilead Sciences, Inc, ViiV Healthcare/GSK, and Merck Sharp & Dohme; and drug-level kits for research use provided to their institution from Ark. C. C.: grant funds from Gilead Sciences, Inc, ViiV Healthcare, and Merck & Co, Inc; and support for attending meetings and/or travel from Gilead Sciences, Inc, and ViiV Healthcare. V. C.: consulting fees to self and their institution from ViiV Healthcare, Gilead Sciences, Inc, Merck & Co, Inc, and Moderna; patent on HHV8-related disease treatment; data safety monitoring boards for academic trials; and stock in SkinDermic. F. C.-S.: payments to their institution from Gilead Sciences, Inc, Merck & Co. Inc, and ViiV Healthcare; and consulting fees from Gilead Sciences, Inc, Merck & Co. Inc, and ViiV Healthcare. H. F. G.: payments to their institution from the Swiss National Science Foundation, Swiss HIV Cohort Study, and the Yvonne Jacob Foundation (a subcontractor to a Bill and Melinda Gates Foundation grant); unrestricted research grants from ViiV Healthcare and Gilead Sciences, Inc; and personal fees for participating in data safety monitoring boards or advisory boards for Merck & Co, Inc, Gilead Sciences, Inc, Johnson and Johnson, GSK, Janssen, and ViiV Healthcare. D. M. J.: employee of IAS–USA. R. P.: funding to their institution from Merck & Co; grants or contracts with Gilead Sciences, Inc, Merck & Co, Inc, PharmaMar, and ViiV Healthcare; and consulting fees from Gilead Sciences, Inc, Pfizer, Inc, Roche Therapeutics, Merck & Co, Inc, GSK, ViiV Healthcare, Eli Lilly and Company, AstraZeneca, Exevir, PharmaMar, and Atea Pharmaceuticals, Inc. R. W. S.: consulting fees from Gilead Sciences, Inc, and GSK; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Gilead Sciences (prior to 2022), Inc, and GSK. D. D. R.: payment to self from Generate Biosciences for participation in an advisory board; payment to self from Gilead Sciences, Inc, for participation in a data safety monitoring board; and an unpaid member of the Board of Directors for the Human Immunome Project. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References

    1. Wensing AM, Calvez V, Ceccherini-Silberstein F, et al. 2025 Update of the drug resistance mutations in HIV-1 [manuscript published online ahead of print 4 March 2025]. Top Antivir Med. - PubMed
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