Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch

Study Overview
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Brief Summary
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Combination antiretroviral therapy (cART) HIV treatments are associated with increased quality of life, and a normalisation of life expectancy in people living with HIV. However, long-term use of cART can lead to side-effects through exposure to drug-related toxicity. For this reason researchers are interested in looking at alternative therapies that might expose patients to fewer and less severe side effects while providing the same quality of care as antiretroviral therapies most often used to treat HIV. The purpose of this study is to investigate if the study drug combination that is being tested (doravirine + dolutegravir) is safe compared with other triple cART regimens.

Detailed Description
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A randomised, open label study to assess the efficacy of switching from suppressive triple cART to doravirine + dolutegravir dual cART in people living with HIV (PLWH) with an undetectable viral load A computer-based software will randomise participants 2:1 to either the (1) experimental arm (early switch group) to take two-pill regimen for 96 weeks, or (2) control arm (delayed switch group) where participants continue their current triple cART regimen for 48 weeks, then switch to the two-pill regimen for another 48 weeks. Viral load will be measured at each study visit to determine the percentage of participants in each treatment arm with undetectable plasma HIV RNA levels at week 48. Additional research urine and bloods will be taken, as well as questionnaires completed at baseline and every 24 weeks to further investigate safety, tolerability, and quality of life from switch of suppressive triple cART to doravirine + dolutegravir dual cART.

Official Title
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Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch (DORDOL)

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Doravirine
* Drug: Dolutegravir
* Other: Triple cART regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected, 18 years or older On stable & suppressive triple cART for at least 6 months No evidence of resistance to DOR or DTG No laboratory abnormalities, medical/psychiatric conditions or alcohol/drug use considered a barrier to participation by investigators Women who are pre-menopausal and sexually active should be on one of the following methods of contraception: Implant Depot injection Intra-uterine device or system Oral hormonal contraception Exclusion Criteria: History of virological failure on an NNRTI in absence of a post-failure genotypic resistance test proving absence of resistance to DOR History of virological failure on an INSTI in absence of a post-failure genotypic resistance test proving absence of resistance to DTG (INSTI mutations that will lead to the need of administering DTG twice-daily are considered as resistance to DTG - and the subject will be considered NOT eligible) Concomitant medication contra-indicated with DTG or DOR Haemoglobin <9 g/dL Platelets <80,000/mm3 Creatinine clearance <30 mL/min AST or ALT ≥5N Acute Hepatitis A infection. Concomitant DAA for anti-HCV therapy Known acute or chronic viral hepatitis B or C. Individuals testing positive for HBcAb, but negative HBsAg/HBeAg, may be included on the trial. Individuals with positive anti-HCV results, but with HCV RNA not detected may be included on the trial. Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate Switch<br>Two-pill regimen, doravirine (100 mg) + dolutegravir (50 mg) tablets taken orally once daily for 96 weeks. | Drug: Doravirine<br>* Antiretroviral, Non-nucleoside Reverse Transcriptase Inhibitor<br>* Other names: Pifeltro;Drug: Dolutegravir<br>* Antiretroviral, Integrase strand transfer inhibitors<br>* Other names: Tivicay;|
| Other: Delayed Switch<br>Participants will continue their current triple cART regimen for 48 weeks. Patients will then be switched to two-pill regimen, doravirine (100 mg) + dolutegravir (50 mg) tablets taken orally once daily for 48 weeks. | Drug: Doravirine<br>* Antiretroviral, Non-nucleoside Reverse Transcriptase Inhibitor<br>* Other names: Pifeltro;Drug: Dolutegravir<br>* Antiretroviral, Integrase strand transfer inhibitors<br>* Other names: Tivicay;Other: Triple cART regimen<br>* Participant standard triple cART regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with undetectable plasma HIV RNA levels at Week 48 | Undetectable will be defined as plasma HIV RNA levels of <50 copies/ml. Any patient with HIV RNA levels >50 copies/ml at analysis time points will have a repeat test | 48 weeks from randomisation (+/- 7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients treated on each treatment arm with HIV viral load less than 50 copies/ml to determine absolute efficacy of study treatments | Proportion of patients treated on each treatment arm with HIV viral load less than 50 copies/ml at weeks and 24, 72 and 96. | 96 weeks from randomisation (+/- 7 days) | 
| Frequency and severity of adverse events to determine safety and tolerability of study treatments | Occurrence of adverse events (including laboratory results), severity of adverse events and occurrence of treatment discontinuations measured through adverse event reporting by sites. | 96 weeks from randomisation (+/- 7 days) | 
| Changes in CD4 count and CD4:CD8 ratio to determine safety and tolerability of study treatments | CD4 count and CD4:CD8 ratio will be measured at screening and compared to measurements in both arms weeks 24, 48, 72 and 96 | 96 weeks from randomisation (+/- 7 days) | 
| Scores from participant-recorded outcome measures on quality of life to determine safety and tolerability of study treatments | Scores from participant-recorded outcome measures at weeks 0, 24, 48, 72 and 96: EuroQoL EQ-5D-3L Questionnaire Score from 0 to 100 (with 100 as best outcome) | 96 weeks from randomisation (+/- 7 days) | 
| Scores from participant-recorded outcome measures on patient treatment satisfaction to determine safety and tolerability of study treatments | Scores from participant-recorded outcome measures at weeks 0, 24, 48, 72 and 96: Patient Treatment Satisfaction Questionnaire At week 0: Score from 0 to 6 (with 6 as best outcome) All other visits: Score -3 to +3 compared to week previous (with higher score best outcome) | 96 weeks from randomisation (+/- 7 days) | 
| Scores from participant-recorded outcome measures on sleep quality to determine safety and tolerability of study treatments | Scores from participant-recorded outcome measures at weeks 0, 24, 48, 72 and 96: Pittsburgh Sleep Quality Index (PSQI) Score range for each PSQI evaluation ranges from 0 to 21 (with 0 as best outcome) | 96 weeks from randomisation (+/- 7 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Doravirine, Dolutegravir, cART