Dolutegravir Plus 3TC in Virologically Suppressed PLWHIV: Immunological Outcomes in a Multicenter Retrospective Cohort in Spain during the COVID-19 Pandemic

Buzón, L; Dueñas, Carlos; Pedrero-Tomé, Roberto; Iribarren, José Antonio; Santos, Ignacio; Santiago, Alberto Díaz de; Morán, Miguel Ángel; Pousada, Guillermo; Moreno-García, Estela; Ferreira, Eva Maria Luiz; Iglesias, Alejandro Villamor; Martín, Cristina Domínguez; Gómez, Julia; Rodríguez, Laura; Egido, M.; Sepulveda, María-Antonia; Troya, Jesús

doi:10.3390/v15020322

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…Eighteen observational studies described 5930 PLWH with VS for six or more months on a wide variety of previous ART regimens who changed their therapy primarily to DTG/3TC or DTG/rilpivirine ( Supplementary Table S5 ) [ 81 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. Sixteen studies were from Western Europe, one was from Turkey, and one was from South Korea.…”

Section: Resultsmentioning

confidence: 99%

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

Chu,

Tao,

Kouamou

et al. 2024

Viruses

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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.

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Section: Resultsmentioning

confidence: 99%

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

Chu,

Tao,

Kouamou

et al. 2024

Viruses

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“…The proportion of individuals with VF defined as a confirmed plasma HIV- Eighteen observational studies described 5930 PLWH with VS for six or more months on a wide variety of previous ART regimens who changed their therapy primarily to DTG/3TC or DTG/rilpivirine (Supplementary Table 5) [83,[100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116]. Sixteen studies were from Western Europe, one was from Turkey, and one was from South Korea.…”

Section: Art-experienced Plwh With Vsmentioning

confidence: 99%

Risk of Emergent Dolutegravir Resistance Mutations In People Living With HIV: A Rapid Scoping Review

Chu,

Tao,

Kouamou

et al. 2024

Preprint

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BackgroundDolutegravir (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 virological failure (VF) with emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART.MethodsWe performed a PubMed search using the term “Dolutegravir” last updated December 18, 2023, to estimate the prevalence of VF with emergent INSTI DRMs in clinical trials and cohorts of people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART.ResultsOf 2131 records identified by search, 43 clinical trials, 39 cohorts, and six cross-sectional studies provided data across six clinical scenarios based upon ART history, virological status, and ARVs co-administered with DTG: (1) ART-naïve PLWH receiving DTG plus two nucleoside reverse transcriptase inhibitors (NRTIs); (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on their 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 proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.6% for scenario 3 and 2.9% for scenario 6. In the remaining four trial scenarios, prevalence of VF with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, while cross-sectional studies yielded prevalence data lacking denominator details.ConclusionsIn 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 the risk of VF with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.What is already known on this topicDolutegravir is known for its high resistance barrier, yet there remains a concern for virological failure and subsequent drug resistance in people living with HIV who begin first or second-line antiretroviral therapy with a dolutegravir-containing regimen.What this study addsThe prevalence of virological failure with the development of HIV mutations associated with reduced susceptibility to dolutegravir depends on a person’s virological response to previous antiretroviral therapy, the presence of HIV replication at dolutegravir initiation, and the antiretroviral drugs co-administered with dolutegravir.In clinical trial settings, the prevalence of virological failure with emergent dolutegravir resistance was rare among people initiating therapy with a dolutegravir-containing regimen and was 1.6% over a period of one to two years among those who had previously experienced virological failure on an earlier treatment regimen.In the subset of persons with virological failure on a first-line dolutegravir-containing regimen, the prevalence of emergent dolutegravir resistance was 0.7%, whereas in the subset of persons with virological failure on a second-line dolutegravir-containing regimen, the prevalence of emergent dolutegravir resistance was 20.4%.How this study might affect research, practice, or policyIn people living with HIV with virological failure on a first-line dolutegravir-containing regimen, enhancing medication adherence may prove more beneficial than transitioning to an alternative treatment regimen.In cases of virological failure on a second-line dolutegravir-containing regimen, the potential for dolutegravir resistance suggests a need to investigate the role of genotypic resistance testing to inform treatment changes.Population-level surveillance for acquired dolutegravir resistance should take into account the antiretroviral treatment history and level of HIV replication prior to the initiation of dolutegravir-containing therapy.

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“…Several studies have explored the effectiveness, safety, and tolerability of DTG/3TC [17][18][19][20][21][22][23][24][25][26][27][28] or TAF/FTC/BIC [29][30][31][32][33][34] in real-world cohorts of virologically suppressed PLWH. However, to date, there are few comparison data on the effectiveness, tolerability, and safety of these regimens as a switch strategy in clinical practice [35][36][37][38] and a lack of comparative randomized studies.…”

Section: Introductionmentioning

confidence: 99%

Dolutegravir/Lamivudine versus Tenofovir Alafenamide/Emtricitabine/Bictegravir as a Switch Strategy in a Real-Life Cohort of Virogically Suppressed People Living with HIV

De Socio,

Tordi,

Altobelli

et al. 2023

JCM

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Background: The aim of the study is to evaluate the effectiveness, safety, and tolerability of a two-drug regimen (2-DR) dolutegravir/lamivudine (DTG/3TC) versus a three-drug regimen (3-DR) tenofovir alafenamide/emtricitabine/bictegravir (TAF/FTC/BIC) in a real-life cohort of HIV-1 virologically suppressed treatment-experienced (TE) people living with HIV (PLWH). Methods: This was a single-center, retrospective, observational study analyzing adult TE PLWH who started the 2-DR or 3-DR between January 2018 and January 2023. All PLWH with a viral load (VL) <50 copies/mL at the time of switching, and a follow-up of more than 6 months or interruption of treatment at any time, were included. Results: A total of 324 PLWH were included; of these, 110 (34%) were on the 2-DR and 214 (66%) were on the 3-DR. Most patients remained on therapy in both groups (93.6% 2-DR versus 90.2% 3-DR) and, at the last control, 99.1% achieved VL < 50 copies/mL with the 2-DR versus 97.2% with the 3-DR (p = 0.260). No virological failures occurred in either group. Adverse events occurred in a few cases: four (3.6%) in the 2-DR group and five (2.3%) in the 3-DR group (p = 0.500). The median follow-up-time was 19.6 months for the 2-DR and 27.5 months for the 3-DR. Conclusion: Our study shows a similar effectiveness and safety profile in virologically suppressed PLWH switching to DTG/3TC or TAF/FTC/BIC.

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Dolutegravir Plus 3TC in Virologically Suppressed PLWHIV: Immunological Outcomes in a Multicenter Retrospective Cohort in Spain during the COVID-19 Pandemic

Cited by 4 publications

References 23 publications

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

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

Risk of Emergent Dolutegravir Resistance Mutations In People Living With HIV: A Rapid Scoping Review

Dolutegravir/Lamivudine versus Tenofovir Alafenamide/Emtricitabine/Bictegravir as a Switch Strategy in a Real-Life Cohort of Virogically Suppressed People Living with HIV

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