Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review
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 rec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/16/3/399 |
| _version_ | 1797239081923510272 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Carolyn Chu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T17:45:52Z |
| format | Article |
| id | doaj.art-34d25c7a03884a529279d268af3e72b0 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-24T17:45:52Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-34d25c7a03884a529279d268af3e72b02024-03-27T14:07:46ZengMDPI AGViruses1999-49152024-03-0116339910.3390/v16030399Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping ReviewCarolyn Chu0Kaiming Tao1Vinie Kouamou2Ava Avalos3Jake Scott4Philip M. Grant5Soo-Yon Rhee6Suzanne M. McCluskey7Michael R. Jordan8Rebecca L. Morgan9Robert W. Shafer10Department of Family and Community Medicine, University of California San Francisco, San Francisco, CA 94110, USADivision of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USAFaculty of Medicine and Health Sciences, University of Zimbabwe, Harare 00263, ZimbabweCareena Center for Health, Gaborone, BotswanaDivision of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USADivision of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USADivision of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USADivision of Infectious Diseases, Harvard Medical School, Boston, MA 02115, USADivision of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USASchool of Medicine, Case Western Reserve University, Cleveland, OH 44106, USADivision of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USABackground: 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.https://www.mdpi.com/1999-4915/16/3/399HIVepidemiologysystematic reviewtreatment |
| spellingShingle | 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 Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review Viruses HIV epidemiology systematic review treatment |
| title | Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review |
| title_full | Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review |
| title_fullStr | Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review |
| title_full_unstemmed | Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review |
| title_short | Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review |
| title_sort | prevalence of emergent dolutegravir resistance mutations in people living with hiv a rapid scoping review |
| topic | HIV epidemiology systematic review treatment |
| url | https://www.mdpi.com/1999-4915/16/3/399 |
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