Real-world efficacy and safety of dolutegravir plus lamivudine versus tenofovir plus lamivudine and efavirenz in ART-naïve HIV-1-infected adults

Li, Jin; Chen, Dabiao; Zhang, Wen; Du, Yanzhang; Huang, Zheping; Zhong, Huijun; Wang, Yanhao; Yin, Sichun

doi:10.1097/md.0000000000031100

Cited by 5 publications

(4 citation statements)

References 24 publications

(47 reference statements)

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“…Three cohort studies included 581 PLWH who received DTG plus 3TC and were followed for a median of 48 weeks [ 39 , 49 , 50 ] ( Supplementary Table S2 ). Two studies were from Spain, and one was from China.…”

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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“…So far, several observational studies have compared the clinical outcomes between TLE and DTG + 3TC or TLE and B/F/TAF in treatmentnaïve individuals, respectively, and all have consistently showed that either DTG + 3TC or B/F/TAF was superior to TLE in terms of rapid decline in VL or regimen persistence. [14][15][16] However, we still lack comparative data in regard to efficacy and safety of DTG + 3TC and B/F/ TAF in ART-naïve individuals in a real-life scenario. Therefore, we conducted this study to fill this knowledge gap.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety profiles of dolutegravir plus lamivudine vs. bictegravir/emtricitabine/tenofovir alafenamide in therapy-naïve adults with HIV-1

Wei,

Li,

et al. 2023

Chinese Medical Journal

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Background: Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China. Methods: This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs. ≥100,000 copies/mL) and CD4+ cell count (<200 vs. ≥200 cell/µL). Median time to TND VL was assessed by Kaplan–Meier method. We also measured changes from baseline in CD4+ cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). Results: We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND (P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) (P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) (P <0.001). No differences were seen in CD4+ cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) (P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. Conclusions: In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4+ cell count. CD4+ recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.

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“…Three cohort studies included 581 PLWH who received DTG plus 3TC and were followed for a median of 48 weeks [39,49,50] (Supplementary Table 2). Two studies were from Spain, and one was from China.…”

Section: Art-naïve Plwhmentioning

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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Real-world efficacy and safety of dolutegravir plus lamivudine versus tenofovir plus lamivudine and efavirenz in ART-naïve HIV-1-infected adults

Cited by 5 publications

References 24 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

Efficacy and safety profiles of dolutegravir plus lamivudine vs. bictegravir/emtricitabine/tenofovir alafenamide in therapy-naïve adults with HIV-1

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

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