HIV-1-infection
Conditions
Keywords
Doravirine, Delstrigo, DOR/3TC/TDF, Women of reproductive potential
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.
Interventions
DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination switched from either EFV/TDF/FTC or DTG/TDF/3TC
Sponsors
Professor Francois Venter
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 fasting lipids from baseline to Week 48 | 48 weeks | Changes in fasting lipids from baseline to Week 48 assessed using lipid profile blood test |
| Changes in weight from baseline to Week 48 | 48 weeks | Changes in weight from baseline to Week 48 assessed |
| 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 glucose from baseline to Week 48 | 48 weeks | Changes in glucose from baseline to Week 48 assessed using blood test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
South Africa
Outcome results
None listed