ADORE: Efficacy of DORavirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With NNRTI Resistance

Study Overview
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Brief Summary
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This is a pilot study investigating the efficacy of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults living with HIV-1 experiencing virological failure on first-line Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance

Detailed Description
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This is a single-arm, phase 3 pilot study investigating the efficacy of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults living with HIV-1 experiencing virological failure on first-line Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance. Approximately 25 male and female participants 18 years and older infected with HIV-1 and experiencing virological failure on efavirenz-based ART will be administered a once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF). The study includes screening and baseline visits, 4 study visits from Week 4 to Week 36, and an end of study visit at Week 48.

Official Title
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ADORE: A Single-arm, Phase 3, Pilot Study Investigating the Efficacy of Doravirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With Non-nucleoside Reverse Transcriptase Inhibitor Resistance

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Doravirine/Lamivudine/Tenofovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults living with HIV-1, 18 years and older Viral load 5000 - 60 000 copies/mL on first-line efavirenz-based antiretroviral therapy HIV genotype resistance test with first generation NNRTI resistance (e.g. K103N, Y181C, etc as listed in the protocol) CD4 > 200 cells/uL Creatinine clearance > 50 mL/min Body mass ≥ 35 kg. Exclusion Criteria: Resistance to TDF on genotype (K65R) Significant resistance to doravirine, denoted by a Stanford Score ≥ 15 on genotype Virologic failure on any other regimen Women who are pregnant at the time of the screening or enrolment visits Active tuberculosis and/or are on anti-tuberculous therapy at the time of the screening or enrolment visits Taking and cannot discontinue prohibited concomitant medications listed in protocol at least two weeks prior to the enrolment visit and for the duration of the study period.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doravirine<br>Once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF). | Drug: Doravirine/Lamivudine/Tenofovir<br>* DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination<br>* Other names: Delstrigo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24 | The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 24 will be recorded. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48 | Evaluation of viral suppression by recording the proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48 | At week 4, 12, 48 | 
| Change from baseline in plasma CD4 levels at weeks 24 and 48 | Evaluation of changes in CD4 count from baseline recorded at weeks 24 and 48. | At week 24, 48 | 
| Emergence of antiretroviral resistance mutations in participants with virological failure | Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Virological failure, first-line antiretroviral therapy, Doravirine, Delstrigo