Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of 2-Drug Therapy With Dolutegravir(DTG)/Rilpivirine(RPV) Fixed Dose Combination(FDC) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With NNRTI Mutation K103N

Summary

HIV-1 infected subjects that experience virological failure while on non nucleoside reverse-transcriptase inhibitors (NNRTIs), including those with the K103N mutation, are usually switched to a boosted Protease Inhibitor (PI)-based regimen or other antiretroviral (ARV) combinations. The same is true for subjects who need to start antiretroviral therapy and have acquired virus that is already resistant to antiretrovirals. These "second line" combinations are often associated with numerous issues that can have a potential impact on the quality of life (QoL) of these patients. Therefore a simpler and better tolerated alternative second line treatment option would be a useful tool for the clinical management of these patients. The aim of this study is to assess the efficacy and tolerability of a dual combined therapy of Dolutegravir (DTG) 50 mg Once Daily (OD) + Rilpivirine (RPV) 25 mg OD in virologically suppressed participants with previous virological failure with NNRTIs and having the clinically significant mutation K103N. The secondary objective of the study is to assess whether a simplification of the treatment in terms of pill burden, long term metabolic toxicity and potential for drug interactions improves the QOL of the participants. The study will also evaluate DTG \& RPV concentrations in the blood plus changes in cell associated virus. In order to compare the first line treatment (boosted PI and/or other antiretroviral combinations) and the DTG+RPV combination, two thirds of study participants will be switched to DTG+RPV immediately and receive DTG+RPV for 96 weeks. The other third will be switched after 48 weeks of continuing on their first line treatment and receive DTG+RPV for 48 weeks. All participants will then be followed up for a further 30 days. Participants will be recruited from sites across Europe, and randomised onto either arm of the study. After randomisation, participants will attend approximately 10 visits over the course of two years.

Timeline

Start

2018-11-05

Primary completion

2021-11-15

Completion

2022-11-09

Publications

• Moyle G, Assoumou L, De Castro N, Post FA, Curran A, Rusconi S, De Wit S, Stephan C, Raffi F, Johnson M, Masia M, Vera J, Jones B, Fletcher C, Morris K, Pozniak A; for NEAT Foundation, WISARD study group. Durable efficacy of dolutegravir/rilpivirine switch in subjects with HIV RNA <50 copies/ml and history of K103N mutation. AIDS. 2026 Jul 1;40(7):885-893. doi: 10.1097/QAD.0000000000004451. Epub 2026 Jan 22.
• Moyle G, Assoumou L, de Castro N, Post FA, Curran A, Rusconi S, De Wit S, Stephan C, Raffi F, Johnson M, Masia M, Vera J, Jones B, Grove R, Fletcher C, Duffy A, Morris K, Pozniak A; NEAT ID Foundation and the WISARD study group. 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. Lancet HIV. 2024 Mar;11(3):e156-e166. doi: 10.1016/S2352-3018(23)00292-8.

Drugs

Indications