Analysing the efficacy and tolerability of dolutegravir plus either rilpivirine or lamivudine in a multicentre cohort of virologically suppressed PLWHIV

Ciccullo, Arturo; Baldin, Gianmaria; Borghi, Vanni; Cossu, MV; Giacomelli, Andrea; Lagi, Filippo; Farinacci, Damiano; Iannone, Valentina; Passerotto, Rosa Anna; Capetti, A; Sterrantino, Gaetana; Mussini, Cristina; Antinori, Spinello; Giambenedetto, Simona Di

doi:10.1093/jac/dkac362

Cited by 7 publications

(10 citation statements)

References 11 publications

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“…In addition, data from the real‐life ODOCARE cohort showed similar efficacy of 2DR DTG‐based regimens and 3DR INSTI‐based regimens in virologically suppressed PLWHIV but with better tolerability [18]. Compared to other 2DR, similar results have been reported with DTG/RPV and DTG/3TC [17, 18], although for patients with extensive experience with ART and prior virological failures, DTG/RPV would be a better option. Data with 2DR with the last available NNRTI doravirine (DOR) are scanty, showing a favourable impact on lipid profile [19], similar to that reported in our cohort with DTG/RPV.…”

Section: Discussionmentioning

confidence: 80%

“…Our results are in line with these data. Cicullo et al [17] have more recently published analysis from a cohort of PLWHIV switching to 2DR DTG-based regimens, which included 286 cases on DTG/RPV and 306 on DTG/3TC; they only observed four virological failures (0.6 per 100 patients-year of follow-up) in the RPV group, and nine (1.4 per 100 patients-year of follow-up) in the 3TC group, with no acquired RAMs. All patients had HIV RNA <50 copies/mL at the start of the study regimen, and they excluded data from PLWHIV with no prior resistance mutation available, which is a relevant difference with our cohort.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of dolutegravir/rilpivirine in real‐world clinical practice. GeSIDA study 1119

et al. 2023

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Introduction Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real‐world clinical practice. Methods Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. Results A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/μL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non‐nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV‐RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1–92.6) by intention‐to‐treat (ITT) and 94.2% (95% CI 91.3–96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low‐density lipoprotein‐cholesterol, glutamic–pyruvic transaminase (GPT), gamma‐glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. Conclusions This study confirms the effectiveness, tolerability and safety of DTG/RPV in real‐world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one‐third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of dolutegravir/rilpivirine in real‐world clinical practice. GeSIDA study 1119

et al. 2023

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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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“…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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Analysing the efficacy and tolerability of dolutegravir plus either rilpivirine or lamivudine in a multicentre cohort of virologically suppressed PLWHIV

Cited by 7 publications

References 11 publications

Efficacy and safety of dolutegravir/rilpivirine in real‐world clinical practice. GeSIDA study 1119

Efficacy and safety of dolutegravir/rilpivirine in real‐world clinical practice. GeSIDA study 1119

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

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