HIV-1-infection
Conditions
Keywords
Virological failure, first-line antiretroviral therapy, Doravirine, Delstrigo
Brief summary
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
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.
Interventions
DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination
Sponsors
Professor Francois Venter
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24 | 24 weeks | The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 24 will be recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48 | At week 4, 12, 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 |
| Change from baseline in plasma CD4 levels at weeks 24 and 48 | At week 24, 48 | Evaluation of changes in CD4 count from baseline recorded at weeks 24 and 48. |
| Emergence of antiretroviral resistance mutations in participants with virological failure | 48 weeks | Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure |
Countries
South Africa
Contacts
Primary ContactSimiso Sokhela, MBBCh
Backup ContactBronwyn Bosch, MBBCh
Outcome results
None listed