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

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

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

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.

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.