High virological suppression regardless of the genotypic susceptibility score after switching to a dolutegravir-based regimen: week 48 results in an observational cohort

Charpentier, Charlotte; Peytavin, Gilles; Lê, Minh Patrick; Joly, Véronique; Cabras, Ornella; Perrier, Marine; Gac, Sylvie Le; Phung, Bao; Yazdanpanah, Yazdan; Descamps, Diane; Landman, Roland

doi:10.1093/jac/dky062

Cited by 15 publications

(8 citation statements)

References 13 publications

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“…To the best of my knowledge, there is no set factor for weighting different INSTIs. More recent studies have, similar to our results, found DTG-based ART to be robust even with GSS < 1.5 (149). However, in both studies, participants with GSS scores in effect close to DTG monotherapy were few.…”

Section: Discussionsupporting

confidence: 90%

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations

Sörstedt

Carlander²,

Flamholc

et al. 2018

International Journal of Antimicrobial Agents

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Until the introduction of dolutegravir (DTG), people living with HIV (PLWH) who have developed nucleoside reverse transcriptase inhibitor (NRTI) mutations have had few other treatment options outside of regimens based on ritonavir-boosted protease inhibitors (PI/r). Here we report treatment results among PLWH in Sweden with pre-existing NRTI mutations on antiretroviral treatment (ART) with DTG and one to two NRTIs. All PLWH on ART with DTG and one to two NRTIs with pre-existing NRTI mutations were retrospectively identified from the National InfCare HIV database. As controls, PLWH on PI/r and one to two NRTIs, matched according to Genotypic Susceptibility Score and observation time, were included. Data were collected as long as the study population was on treatment with DTG; controls were monitored for the same interval. Outcome was classified as either treatment success or failure. In total, 244 participants (122 individuals treated with DTG and 122 individuals treated with PI/r) were included. Median observation time was 78 weeks (interquartile range 50-98 weeks) for participants on DTG and 75 weeks (50-101 weeks) for individuals on PI/r. Viral failure was detected in four individuals treated with DTG and three individuals treated with PI/r, resulting in similar success rates of 96.7% and 97.5%, respectively. No new mutations were found among participants with treatment failure. DTG in combination with one to two NRTIs was as efficient as PI/r in individuals with pre-existing NRTI mutations in this setting. It may be considered an alternative to PI/r-based ART even in the presence of NRTI resistance.

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Section: Discussionsupporting

confidence: 90%

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations

Sörstedt

Carlander²,

Flamholc

et al. 2018

International Journal of Antimicrobial Agents

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“…The ART-PRO study reported that no participants experienced virological failure when integrase-inhibitor-naïve, virologically suppressed patients were switched to dual therapy with dolutegravir plus lamivudine, even though 21 of the 41 participants had lamivudine resistance mutations in historical plasma genotypes( 24 ). Similar findings were reported in switch studies evaluating lamivudine and dolutegravir dual therapy( 25 ) and dolutegravir with companion drugs to which resistance was documented( 26 ). The efficacy of TLD in our study, despite resistance to one or both of tenofovir and lamivudine in 89% of our participants, may be attributable to the crippling effect that NRTI mutations have on viral fitness, resulting in residual antiviral activity( 13 ).…”

Section: Discussionsupporting

confidence: 84%

Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen

Keene

Griesel

Zhao

et al. 2021

Aids

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Objective Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine. Design Single arm, prospective, interventional study Setting Two primary care clinics in Khayelitsha, South Africa Participants 60 adult patients with two viral loads (VL)>1000 copies/mL Intervention Participants were switched to TLD with additional dolutegravir (50mg) for two weeks to overcome efavirenz induction. Primary outcome Proportion achieving VL<50 copies/mL at week 24 using the FDA snapshot algorithm. Results Baseline median CD4 count was 248 cells/mm 3 , VL 10580 copies/mL and 48/54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51/60 (85%, 95% CI 73-93%) were virologically suppressed, six had VL 50-100 copies/mL, one VL 100-1000 copies/mL, one no VL in window, and one switched due to tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29/35 (83%, 95% CI 66-93%) with resistance to tenofovir and XTC, 11/13 (85%, 95% CI 55-98%) with resistance to XTC, and 6/6 (100%, 95% CI 54-100%) with resistance to neither. Conclusion A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/mL). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option.

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“…Also, NRTI resistance may prevent the emergence of DTG resistance [12]. Other trials and observational studies have also found DTG, or the similar drug bictegravir, combined with fewer than one active NRTI, to be effective, though typically as a switch strategy in the setting of virologic suppression, which makes the current study findings even more notable [13][14][15].…”

mentioning

confidence: 61%

Growing data for recycling tenofovir and lamivudine with dolutegravir as empiric second-line antiretroviral therapy in resource-limited settings

Marukutira

Wood

2021

Aids

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High virological suppression regardless of the genotypic susceptibility score after switching to a dolutegravir-based regimen: week 48 results in an observational cohort

Abstract: This observational cohort study showed a high level of virological suppression maintenance in the first year following the switch to a dolutegravir-based regimen, even in patients with GSS ≤2.

Cited by 15 publications

References 13 publications

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations

Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen

Growing data for recycling tenofovir and lamivudine with dolutegravir as empiric second-line antiretroviral therapy in resource-limited settings

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