Impact of resistance mutations on efficacy of dolutegravir plus rilpivirine or plus lamivudine as maintenance regimens: a cohort study

Gagliardini, Roberta; Baccini, Michela; Modica, Sara; Montagnani, Francesca; Zanelli, Giacomo; Borghetti, Alberto; Dreassi, Emanuela; Lombardi, Francesca; Pecorari, Monica; Borghi, Vanni; Callegaro, Annapaola; Micheli, Valeria; Lodi, Marco; Rossetti, Barbara; Zazzi, Maurizio

doi:10.1016/j.jgar.2022.01.018

Journal of Global Antimicrobial Resistance

2022

DOI: 10.1016/j.jgar.2022.01.018

|View full text |Cite

Impact of resistance mutations on efficacy of dolutegravir plus rilpivirine or plus lamivudine as maintenance regimens: a cohort study

Roberta Gagliardini

Michela Baccini

Sara Modica

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2022

2024

Publication Types

Select...

Article4

Relationship

Self Cite0

Independent4

Authors

Journals

Cited by 4 publications

(1 citation statement)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These aspects complicated isolating the effectiveness of DTG/3TC in clinical practice. Only 1 cohort (Antiretroviral Resistance Cohort Analysis database (ARCA)) on off-label DTG/3TC use in PWH with resistance had matched controls [ 13 ]. This study pooled PWH on DTG/3TC and DTG with rilpivirine without disaggregating the treatment outcomes to DTG/3TC use.…”

mentioning

confidence: 99%

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study

Vasylyev,

Wit,

Jordans

et al. 2024

Open Forum Infectious Diseases

View full text Add to dashboard Cite

Background Confirming the efficacy of dolutegravir/lamivudine in clinical practice with matched controls on suppressive triple-drug antiretroviral regimens would solidify recommendations on its use. Methods DUALING was a prospective cohort study in 24 HIV treatment centers in the Netherlands. HIV-RNA suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+T-cell nadir and HIV-RNA zenith. Follow-up was calendar time-synchronized between matched pairs. The primary endpoint was the treatment failure rate in cases on dolutegravir/lamivudine and controls on continued dolutegravir-based triple-drug antiretroviral regimens at 1 year by intention-to-treat (missing data=failure) and on-treatment analyses with 5% non-inferiority margin. Results The 2040 participants were 680 cases (390 dolutegravir-based and 290 non-dolutegravir-based regimens) and 1380 controls. Treatment failure in the dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference:-3.78%, 95%CI:-7.49%-0.08%) by intention-to-treat and 1.39% and 0.80% (difference:0.59% 95%CI:-0.80%-1.98%) by on-treatment analyses. The treatment failure risk in non-dolutegravir-based cases was also non-inferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure defined as 2 consecutive HIV-RNA>50copies/mL occurred in 4 cases and 5 controls but without genotypic resistance detected. Other treatment outcomes of clinical interest indicated a comparable low viral blip rate in cases and controls but more weight gain in cases, especially when tenofovir-based regimens were discontinued. Conclusions In routine care, dolutegravir/lamivudine was non-inferior to continuing triple-drug antiretroviral regimens after 1 year. This supports the use of dolutegravir/lamivudine in clinical practice.

show abstract

mentioning

confidence: 99%

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study

Vasylyev,

Wit,

Jordans

et al. 2024

Open Forum Infectious Diseases

View full text Add to dashboard Cite

show abstract

Virological efficacy of switch to DTG plus 3TC in a retrospective observational cohort of suppressed HIV-1 patients with or without past M184V: the LAMRES study

Santoro¹,

Armenia²,

Teyssou³

et al. 2022

Journal of Global Antimicrobial Resistance

View full text Add to dashboard Cite

Evaluation of integrase resistance in individuals who failed a regimen containing dolutegravir in French and Italian clinical settings

Armenia

Santoro

Charpentier

et al. 2023

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

Background This work aims to evaluate integrase resistance and its predictors in HIV-1 infected combined antiretroviral therapy (cART) experienced individuals failing a dolutegravir-based regimen. Methods Major resistance mutations (MRM) and genotypic susceptibility score (GSS) of dolutegravir companion drugs were evaluated on plasma genotypic resistance test (GRT) performed at dolutegravir failure. Logistic regression was used to evaluate factors associated to the risk of integrase strand-transfer inhibitors (INSTI)-resistance at dolutegravir failure. Results We retrospectively analysed 467 individuals. At failure GRT, individuals had been under dolutegravir for a median (IQR) time of 11 (5–20) months; around half of them had never been exposed to INSTI (52%) and 10.7% were at first-line regimen. Fifty-eight (12.4%) individuals showed ≥1 INSTI MRM. Among them, people INSTI-exposed showed significantly higher prevalence of INSTI resistance compared to those who were INSTI naïve [46 (21.2%) versus 9 (3.9%), P < 0.001]. N155H was the most prevalent MRM (5.4%), followed by G140S (4.5%) and Q148H (4.3%). These MRM were more probably present in INSTI-experienced individuals compared to those INSTI naïve. Despite failure, 89.5% of individuals harboured viral strains fully susceptible to dolutegravir and bictegravir and 85.0% to all INSTI. No INSTI exposure before receiving dolutegravir [OR: 0.35 (0.16–0.78), P < 0.010] and a GSS for companion drugs ≥2 (OR: 0.09 [0.04–0.23], P < 0.001) were negatively associated with INSTI resistance at failure. Conclusions In a large set of individuals failing dolutegravir in real-life, INSTI resistance was low and mainly related to previous first-generation INSTI exposure. Surveillance of integrase resistance remains crucial to preserve efficacy of INSTI class in the future.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Impact of resistance mutations on efficacy of dolutegravir plus rilpivirine or plus lamivudine as maintenance regimens: a cohort study

Cited by 4 publications

References 24 publications

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study

Virological efficacy of switch to DTG plus 3TC in a retrospective observational cohort of suppressed HIV-1 patients with or without past M184V: the LAMRES study

Evaluation of integrase resistance in individuals who failed a regimen containing dolutegravir in French and Italian clinical settings

Contact Info

Product

Resources

About