DORA: A Doravirine-based First-line Antiretroviral Therapy for Women of Reproductive Potential Living With HIV

Professor Francois Venter133 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

133

Conditions

HIV-1-infection

Interventions

Doravirine/Lamivudine/Tenofovir Disoproxil FumarateDRUG

DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination switched from either EFV/TDF/FTC or DTG/TDF/3TC

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 49 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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).

Locations (2)

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, Gauteng, South Africa

Sunnyside Office Park

Johannesburg, Gauteng, South Africa

Outcomes

Primary Outcomes

The proportion of participants with neuropsychiatric adverse events (AEs)

The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 48

Time frame: 48 weeks

Changes in fasting lipids from baseline to Week 48

Changes in fasting lipids from baseline to Week 48 assessed using lipid profile blood test

Time frame: 48 weeks

Changes in weight from baseline to Week 48

Changes in weight from baseline to Week 48 assessed

Time frame: 48 weeks

Changes in body mass index from baseline to Week 48

Changes in body mass index from baseline to Week 48 assessed

Time frame: 48 weeks

Changes in glucose from baseline to Week 48

Changes in glucose from baseline to Week 48 assessed using blood test

Time frame: 48 weeks

Secondary Outcomes

The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL)

The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL) at weeks 24 and 48

Time frame: At week 24, 48

The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories

The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 24

Data from ClinicalTrials.gov

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