Switching to dolutegravir plus rilpivirine versus maintaining current antiretroviral therapy regimen in virologically suppressed people with HIV-1 and the Lys103Asn (K103N) mutation: 48-week results from a randomised, open-label pilot clinical trial.

Journal

The lancet. HIV

ISSN: 2352-3018

Titre abrégé: Lancet HIV

Pays: Netherlands

ID NLM: 101645355

Informations de publication

Date de publication:
Mar 2024

Historique:

received: 09 05 2023

revised: 26 10 2023

accepted: 30 10 2023

medline: 29 2 2024

pubmed: 29 2 2024

entrez: 28 2 2024

Statut: ppublish

Résumé

The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens. In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38. Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups. Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine. ViiV Healthcare.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38.

FINDINGS RESULTS

Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups.

INTERPRETATION CONCLUSIONS

Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine.

FUNDING BACKGROUND

ViiV Healthcare.

Identifiants

DOI: 10.1016/S2352-3018(23)00292-8 PMID: 38417976

pubmed: 38417976

pii: S2352-3018(23)00292-8

doi: 10.1016/S2352-3018(23)00292-8

pii:

doi:

Banques de données

ClinicalTrials.gov

['NCT05349838']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

e156-e166

Investigateurs

Graeme Moyle (G)

Nathalie de Castro (N)

Frank Post (F)

Adrian Curran (A)

Stefano Rusconi (S)

Stephane De Wit (S)

Christoph Stephan (C)

François Raffi (F)

Margaret Johnson (M)

Mar Masia (M)

Jaime Vera (J)

Alan Winston (A)

Stephen Kegg (S)

Laura Waters (L)

Chole Orkin (C)

Andrew Ustianowski (A)

Iain Reeves (I)

Clifford Leen (C)

Meghan Perry (M)

Joaquin Portilla (J)

Jose Luis Blanco (JL)

Rocio Montejaro (R)

Pere Domingo (P)

Jean Michel Molina (JM)

Christine Katlama (C)

Philippe Morlat (P)

Christopher Kenyon (C)

Massimo Puoti (M)

Giuliano Rizzardini (G)

Antonella Castagna (A)

Francesco Castelli (F)

Andrea Giacomelli (A)

Jürgen Rockstroh (J)

Stefan Esser (S)

Christian Hoffmann (C)

Patrick Mallon (P)

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of interests GM has received fees for educational activities or advisory services from Gilead, Merck Sharp & Dohme, Theratechnologies, and ViiV Healthcare. AC has received fees for educational activities and consultancies, and financial support for attending conferences from Gilead, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare. SR has received honoraria for presentations and scientific advice from Merck Sharp & Dohme, Theratechnologies, GSK, Janssen Cilag, ViiV Healthcare, and Gilead, and research grants paid to his institution from Janssen Cilag, ViiV Healthcare, and Gilead. MM has participated in lectures and advisory boards for ViiV Healthcare, Janssen, and MSD. BJ is a ViiV Healthcare employee and holds GSK stock. RG is an employee of GSK and owns shares in the company. AP has delivered lectures and participated in advisory boards for ViiV Healthcare, Janssen, Gilead, and MSD. All other authors declare no competing interests.