Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review

Carolyn Chu; Kaiming Tao; Vinie Kouamou; Ava Avalos; Jake Scott; Philip M. Grant; Soo-Yon Rhee; Suzanne M. McCluskey; Michael R. Jordan; Rebecca L. Morgan; Robert W. Shafer

doi:10.3390/v16030399

Viruses (Mar 2024)

Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review

Carolyn Chu,
Kaiming Tao,
Vinie Kouamou,
Ava Avalos,
Jake Scott,
Philip M. Grant,
Soo-Yon Rhee,
Suzanne M. McCluskey,
Michael R. Jordan,
Rebecca L. Morgan,
Robert W. Shafer

Affiliations

Carolyn Chu: Department of Family and Community Medicine, University of California San Francisco, San Francisco, CA 94110, USA
Kaiming Tao: Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
Vinie Kouamou: Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare 00263, Zimbabwe
Ava Avalos: Careena Center for Health, Gaborone, Botswana
Jake Scott: Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
Philip M. Grant: Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
Soo-Yon Rhee: Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
Suzanne M. McCluskey: Division of Infectious Diseases, Harvard Medical School, Boston, MA 02115, USA
Michael R. Jordan: Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA
Rebecca L. Morgan: School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
Robert W. Shafer: Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA

DOI: https://doi.org/10.3390/v16030399
Journal volume & issue: Vol. 16, no. 3
p. 399

Abstract

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Background: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART. Methods: We performed a PubMed search using the term “Dolutegravir”, last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART. Results: Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details. Conclusions: In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.

Published in Viruses

ISSN: 1999-4915 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/viruses

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