Switching to DTG/3TC in virologically suppressed HIV-infected adults
Research type
Research Study
Full title
A Phase III, randomized, multicenter, open-label, non-inferiority study evaluating the efficacy, safety and tolerability of switching to dolutegravir/lamivudine fixed dose combination in HIV-1 infected adults who are virologically suppressed
IRAS ID
265213
Contact name
Stephen Taylor
Contact email
Sponsor organisation
ViiV Healthcare UK Limited
Eudract number
2018-000177-72
Duration of Study in the UK
2 years, 0 months, 19 days
Research summary
Research Summary
The purpose of this study is to look at a new fixed-dose combination (FDC) for the treatment of HIV. The study will investigate a FDC of dolutegravir (DTG) plus lamivudine (3TC), in comparison to a 3 or more-drug current anti-retroviral regimen (CAR) in people with HIV who are virologically suppressed, potentially reducing the long-term toxicity and future drug-drug interactions. The FDC of DTG and 3TC has been approved in the EU for the treatment of HIV-1 infection in adults and adolescents with no known or suspected resistance to the integrase inhibitor class or lamivudine.
Participants will be assigned by chance into two treatment groups, at a 1:1 ratio. On Day 1, one group of about 300 participants will switch from CAR to DTG/3TC FDC and continue for approximately 52 weeks. Another group will continue to take CAR for approximately 52 weeks.
The study doctor, staff and participant will know to which group they are assigned. Participants assigned to take DTG/3TC FDC, will take one tablet each day at approximately the same time, with or without food. Participants assigned to continue CAR will continue to take these medications as prescribed. The effects of the drugs (good and bad) will be compared.
After 52 weeks, if the participant is taking DTG/3TC FDC, they may choose to stay on DTG/3TC FDC. If the participant is taking CAR, they will complete the study at Week 52.
The study involves assessments including: physical exams, cardiovascular risk assessment, vital signs, electrocardiogram (ECG), questionnaires, blood and urine tests and questions about how the participant is feeling and about the medications they are taking.
This study is sponsored by ViiV Healthcare and has a global target population of 600 participants located in about 131 sites globally. Approximately 22 patients will be based in the UK across 11 hospitals.Summary of Results
Study doctors collected blood samples and measured participants’ viral loads.
In the Randomised Phase, the study compared the number of participants in the two treatment groups, who had a detectable viral load (50 c/mL or more) at Week 48.
One of 246 participants (less than 1%) in the DTG and 3TC group and three of 247 participants (1%) in the CAR group had a detectable viral load at Week 48.
The study also compared the percentage of participants in the two treatment groups, who had an undetectable viral load (less than 50 c/mL) at Week 48.
At Week 48, there were 13 participants (5%) in the DTG and 3TC group and 15 participants (6%) in the CAR group with no results. These participants had left the study or missed the Week 48 visit.
Out of 246 participants in the DTG and 3TC group, 96 (39%) participants entered the Continuation Phase. All participants completed the study and transitioned to locally available DTG/3TC. One participant was withdrawn during the Continuation Phase due to a detectable viral load (50 c/mL or more). At the end of Continuation Phase, no participant had detectable viral load (50 c/mL or more).
No serious side effects were reported in the study.
Non-serious side effects are side effects that do not result in death, hospitalisation or disability. These were reported by 48 participants (20%) in the DTG and 3TC group,16 participants (6%) in the CAR group in the Randomised Phase and 6 participants (6%) in the Continuation Phase.
The study showed that participants who switched to a combination tablet of DTG and 3TC had a similar response in maintaining an undetectable viral load compared with participants who continued taking CAR. The Continuation Phase also showed similar results to that of Randomised Phase and thus supporting switching to DTG/3TC was an effective treatment option.
The side effects reported in this study were as expected. More participants in the DTG and 3TC group reported side effects compared with those in the CAR group. This could be because participants in the CAR group continued receiving their current medicines and were stable for several months before starting the study, while those in the DTG and 3TC group had started new medicines. The DTG/3TC medicine was well tolerated during the Continuation Phase. This was a phase III study. Phase III studies collect information about how well new medicines work and how safe they are.REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
19/EM/0220
Date of REC Opinion
14 Aug 2019
REC opinion
Further Information Favourable Opinion