HIV-1-infection
Conditions
Keywords
Doravirine
Brief summary
This study aims to evaluate the ability of Doravirine to penetrate the genital tract and suppress viral replication and provide evidence for the use of Doravirine as part of treatment strategies as prevention.
Detailed description
Objectives: * To determine Doravirine concentrations in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals receiving antiretroviral therapy (ATR) with Doravirine plus Descovy®. * To evaluate HIV-1 viral load in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals receiving ART with Doravirine plus Descovy®. Study Phase: Phase II Study Design: Open label, single arm, single center, prospective study. Study Disease: HIV-1 infection Study Endpoints: * Concentration of Doravirine in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals, respectively, 8 weeks after switching to Doravirine plus Descovy®. * HIV-1 RNA in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals, respectively, 8 weeks after switching to Doravirine plus Descovy®. Target Population: Male and female adult HIV-1 infected patients receiving standard ART with tenofovir alafenamide/emtricitabine (TAF/FTC), tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine , plus an non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an integrase inhibitor during at least 3 months, with plasma HIV-1 RNA suppression (\<40 copies/mL) during at least 6 months. Number of Subjects Planned: 15 male and 15 female individuals. Study duration: 16 weeks
Interventions
DRUGDoravirine
Doravirine 100 mg tablet
DRUGDescovy
Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet
Sponsors
Institut d'Investigació Biomèdica de Bellvitge
Hospital Universitari de Bellvitge
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients with Doravirine administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) co-formulated as single tablet (Descovy® TAF/FTC) and administered orally once daily.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Asymptomatic, HIV-1 infected individuals ≥ 18 years of age. 2. Be on a stable ART consisting of TAF/FTC, tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, plus an non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an integrase inhibitor, continuously for at least 3 consecutive months preceding the screening visit. 3. Plasma HIV-1 RNA \<40 copies/mL for at least 6 months at the Screening visit. 4. Signed and dated written informed consent prior to inclusion. 5. Female Subjects of Childbearing Potential must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study.
Exclusion criteria
1. Severe hepatic impairment (Child-Pugh Class C) 2. Ongoing malignancy 3. Active opportunistic infection 4. Resistance to any of the antiretroviral (ARV) included in the study or history of virologic failure with risk of resistance selection to any of the study drugs. 5. Any verified Grade 4 laboratory abnormality 6. ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN 7. Severe renal impairment (Estimated creatinine filtration rate \<50mL/min). 8. Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Doravirine in Seminal Plasma Fluid | 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC | Concentration of Doravirine in seminal plasma fluid in HIV-1 infected male individuals |
| Concentration of Doravirine in Cervicovaginal Fluid | 8 weeks after switching to Doravirine plus TAF/FTC | Concentration of Doravirine in cervicovaginal fluid in HIV-1 infected female individuals |
| Number of Participants With HIV-1 RNA Seminal Plasma <40 Copies/mL | 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC | Number of participants with HIV-1 RNA seminal plasma \<40 Copies / mL of HIV measured by real-Time Reverse Transcriptase Polymerase Chain Reaction Amplification |
| Quantification of Participants With HIV-1 RNA <40 Copies / mL in Cervicovaginal Fluid | 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC | Number of participants with HIV-1 RNA cervicovaginal fluid\<40 Copies / mL of HIV measured by real-Time Reverse Transcriptase Polymerase Chain Reaction Amplification |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doravirine + Descovy® TAF/FTC Doravirine (MK-1439) 100 mg administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) co-formulated as single tablet (Descovy® TAF/FTC 25/200 mg) and administered orally once daily during 16 weeks
Doravirine: Doravirine 100 mg tablet
Descovy: Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Doravirine + Descovy® TAF/FTC |
|---|---|
| Age, Continuous | 41 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment Spain | 30 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 18 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Concentration of Doravirine in Cervicovaginal Fluid
Concentration of Doravirine in cervicovaginal fluid in HIV-1 infected female individuals
Time frame: 8 weeks after switching to Doravirine plus TAF/FTC
Population: Descriptive analysis was performed for female participants (14), defining median and IQR of Doravirine concentrations in CVF
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doravirine + Descovy® TAF/FTC | Concentration of Doravirine in Cervicovaginal Fluid | 505.8 ng/ml |
Primary
Concentration of Doravirine in Seminal Plasma Fluid
Concentration of Doravirine in seminal plasma fluid in HIV-1 infected male individuals
Time frame: 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC
Population: Descriptive analysis was performed for male participants (15), defining median and IQR of Doravirine concentrations in seminal plasma
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doravirine + Descovy® TAF/FTC | Concentration of Doravirine in Seminal Plasma Fluid | 127 ng/ml |
Primary
Number of Participants With HIV-1 RNA Seminal Plasma <40 Copies/mL
Number of participants with HIV-1 RNA seminal plasma \<40 Copies / mL of HIV measured by real-Time Reverse Transcriptase Polymerase Chain Reaction Amplification
Time frame: 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC
Population: Number of patients with HIV-1 RNA seminal plasma \<40 copies/ml
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine + Descovy® TAF/FTC | Number of Participants With HIV-1 RNA Seminal Plasma <40 Copies/mL | 15 Number of participants |
Primary
Quantification of Participants With HIV-1 RNA <40 Copies / mL in Cervicovaginal Fluid
Number of participants with HIV-1 RNA cervicovaginal fluid\<40 Copies / mL of HIV measured by real-Time Reverse Transcriptase Polymerase Chain Reaction Amplification
Time frame: 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC
Population: Number of patients with HIV-1 RNA cervicovaginal fluid \<40 copies/ml
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine + Descovy® TAF/FTC | Quantification of Participants With HIV-1 RNA <40 Copies / mL in Cervicovaginal Fluid | 14 Number of participants |