DORA: A Doravirine-based First-line Antiretroviral Therapy for Women of Reproductive Potential Living With HIV
- Conditions
- HIV-1-infection
- Interventions
- Registration Number
- NCT04433780
- Lead Sponsor
- Professor Francois Venter
- Brief Summary
This is a pilot study investigating the safety of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in women of reproductive potential living with HIV-1 switched from Efavirenz or Dolutegravir-based antiretroviral therapy on metabolic and neuropsychiatric outcomes.
- Detailed Description
This is a pilot, open label, single-arm, single centre, phase 3, switch study exploring the safety of of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in women of reproductive potential living with HIV-1 switched from Efavirenz or Dolutegravir-based antiretroviral therapy. The metabolic and neuropsychiatric outcomes among women (and their infants) in a representative African female population of reproductive potential will be investigated.
Approximately 100 women aged between 18 and 49 years old 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 133
- Females, aged 18-49 years and ≥ 40 kg
- On a first-line EFV or DTG-containing regimen for at least six months and not more than 3 years
- Plasma HIV-1 RNA < 50 copies/mL in last 60 days
- Calculated creatinine clearance (CrCl) > 50 mL/min (Cockcroft-Gault formula)
- Baseline weight measurement available at ART initiation.
- Virological failure on any other regimen
- Women who are pregnant at the time of the screening or enrolment visits or have had a pregnancy gestation ≥ 28 weeks in the preceding 2 years
- Active tuberculosis and/or are on antituberculosis 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 (see potential drug interactions section for list).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Delstrigo Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF).
- Primary Outcome Measures
Name Time Method Changes in fasting lipids from baseline to Week 48 48 weeks Changes in fasting lipids from baseline to Week 48 assessed using lipid profile blood test
The proportion of participants with neuropsychiatric adverse events (AEs) 48 weeks The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 48
Changes in body mass index from baseline to Week 48 48 weeks Changes in body mass index from baseline to Week 48 assessed
Changes in weight from baseline to Week 48 48 weeks Changes in weight from baseline to Week 48 assessed
Changes in glucose from baseline to Week 48 48 weeks Changes in glucose from baseline to Week 48 assessed using blood test
- Secondary Outcome Measures
Name Time Method Emergence of antiretroviral resistance mutations in participants with virological failure 48 weeks Evaluating the number of antiretroviral resistance mutations that emerge in participants with virological failure
The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL) At week 24, 48 The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL) at weeks 24 and 48
The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories 24 weeks The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 24
Changes in glucose from baseline to week 24 24 weeks Changes in glucose from baseline to Week 24 using blood test
Changes in fasting lipids from baseline to week 24 24 weeks Changes in fasting lipids from baseline to Week 24 using lipid profile blood test
Changes in weight and from baseline to week 24 24 weeks Changes in weight from baseline to Week 24
Changes in body mass index from baseline to week 24 24 weeks Changes in body mass index from baseline to Week 24
The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR) 48 weeks The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR)
Changes in quality of life from baseline At weeks 24, 48 Changes in quality of life from baseline to Weeks 24 and 48 measured using a traditional clinical, validated quality of life questionairre. Higher scores mean a better outcome
Median adherence by each adherence measure At weeks 24, 48 Median adherence by each adherence measure at Weeks 24 and 48 using a validated adherence questionairre
Trial Locations
- Locations (2)
Charlotte Maxeke Johannesburg Academic Hospital
🇿🇦Johannesburg, Gauteng, South Africa
Sunnyside Office Park
🇿🇦Johannesburg, Gauteng, South Africa