HIV-1-infection, Solid Organ Transplant
Conditions
Brief summary
The aims of this study are to obtain pharmacokinetic data on interactions between dolutegravir (DTG) and immunosuppressant drugs (Cyclosporine A, Tacrolimus, Sirolimus and Mycophenolic acid) in solid organ transplant (SOT) recipients to provide proof of principle data that DTG plus 2 nucleosides (NUCs) is safe and effective in HIV-infected SOT recipients.
Interventions
Lamivudine 300 MG/day (48 weeks)
DRUGAbacavir 600 MG
Abacavir 600 MG/day (48 weeks)
Dolutegravir 50 MG/day (48 weeks)
DRUGTenofovir Disoproxil 245Mg Tablet
Tenofovir 245 MG/day (48 weeks)
Emtricitabine 200 MG/day (48 weeks)
Sponsors
Fundacion Clinic per a la Recerca Biomédica
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. HIV patients \>18 years old who provide signed and dated informed consent; 2. Males and females; 3. SOT recipients (heart, liver or kidney); 4. On stable antiretroviral therapy (ART) for ≥6 months preceding the screening visit; 5. Plasma HIV RNA \<50 cop/ml for 12 months (2 tests separated by at least 12 months with no viral load \>50 between determinations); 6. Absence of major reverse transcriptase or integrase gene mutations affecting study drug efficacy by proviral DNA sequencing
Exclusion criteria
1. HIV patients who have stopped ART due to virological failure; 2. HIV patients who require treatment with DTG contraindicated medications; 3. History or presence of an allergy or intolerance to the study drug; 4. Active opportunistic infection; 5. Neoplasms requiring chemotherapy. 6. Pregnancy or breast feeding or planned pregnancy during the study period 7. Any other contraindication to study drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant | 24-hours before the switch and 24-hours 2 weeks after switching | Change in pharmacokinetic parameters (Cmax, Cmin) of immunosuppressant Cyclosporine A (CsA) |
| Change in Pharmacokinetic Parameters (Cmax, Cmin) of MPA Immunosuppressant | 24-hours before the switch and 24-hours 2 weeks after switching | Change in pharmacokinetic parameters (Cmax, Cmin) of immunosuppressant Mycophenolic Acid (MPA). |
| Change in Pharmacokinetic Parameters (Cmax, Cmin) of Tacrolimus Immunosuppressant | 24-hours before the switch and 24-hours 2 weeks after switching | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Function | week 48 | To assess creatinine \>normal valors mg/dl\> 120 mg/dl |
| Viral Resistance | week 48 | number op patients with VIH viral load \> 50 copies/mL virological failure. |
| Safety: Number AEs and SAEs | week 48 | number AEs and SAEs |
| Changes in CD4+ Cell | week 48 | To assess the changes in CD4+ cell count \>200 cel/mL in peripheral blood. |
| Lipid Profile | week 48 | To assess the changes in lipid profile (triglycerides) |
Countries
Spain
Participant flow
Pre-assignment details
HIV-1-infected adults (\>18) with kidney, liver, or heart transplant, on stable ART ≥6 months, HIV RNA \<50 c/mL for 12 months, no major resistance mutations, and HLA-B\*5701 negative. Some participants had switched to DTG + 2 NRTIs within the 48 weeks prior to study inclusion, while others switched at the time of enrollment. All participants were followed for 48 weeks from the start of DTG-based ART.
Participants by arm
| Arm | Count |
|---|---|
| DTG + 2 NRTIs Dolutegravir plus 2 NRTIs in HIV-1-infected solid organ transplant recipients | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
Baseline characteristics
| Characteristic | DTG + 2 NRTIs |
|---|---|
| Age, Continuous | 57 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 | 19 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 15 / 19 |
| serious Total, serious adverse events | 1 / 19 |
Outcome results
Primary
Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant
Change in pharmacokinetic parameters (Cmax, Cmin) of immunosuppressant Cyclosporine A (CsA)
Time frame: 24-hours before the switch and 24-hours 2 weeks after switching
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pharmacokinetic (PK) Subset Before ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant | Cmax | 825 ng/mL |
| Pharmacokinetic (PK) Subset Before ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant | Cmin | 86.5 ng/mL |
| Pharmacokinetic (PK) Subset After 2wk ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant | Cmax | 299 ng/mL |
| Pharmacokinetic (PK) Subset After 2wk ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant | Cmin | 98.5 ng/mL |
Primary
Change in Pharmacokinetic Parameters (Cmax, Cmin) of MPA Immunosuppressant
Change in pharmacokinetic parameters (Cmax, Cmin) of immunosuppressant Mycophenolic Acid (MPA).
Time frame: 24-hours before the switch and 24-hours 2 weeks after switching
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pharmacokinetic (PK) Subset Before ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of MPA Immunosuppressant | Cmax | 6.3 μg/mL |
| Pharmacokinetic (PK) Subset Before ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of MPA Immunosuppressant | Cmin | 1.9 μg/mL |
| Pharmacokinetic (PK) Subset After 2wk ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of MPA Immunosuppressant | Cmax | 10.3 μg/mL |
| Pharmacokinetic (PK) Subset After 2wk ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of MPA Immunosuppressant | Cmin | 2.9 μg/mL |
Primary
Change in Pharmacokinetic Parameters (Cmax, Cmin) of Tacrolimus Immunosuppressant
Time frame: 24-hours before the switch and 24-hours 2 weeks after switching
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pharmacokinetic (PK) Subset Before ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of Tacrolimus Immunosuppressant | Cmax | 14.4 ng/mL |
| Pharmacokinetic (PK) Subset Before ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of Tacrolimus Immunosuppressant | Cmin | 6.2 ng/mL |
| Pharmacokinetic (PK) Subset After 2wk ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of Tacrolimus Immunosuppressant | Cmax | 16.4 ng/mL |
| Pharmacokinetic (PK) Subset After 2wk ART Change | Change in Pharmacokinetic Parameters (Cmax, Cmin) of Tacrolimus Immunosuppressant | Cmin | 4.4 ng/mL |
Secondary
Changes in CD4+ Cell
To assess the changes in CD4+ cell count \>200 cel/mL in peripheral blood.
Time frame: week 48
Secondary
Lipid Profile
To assess the changes in lipid profile (triglycerides)
Time frame: week 48
Secondary
Renal Function
To assess creatinine \>normal valors mg/dl\> 120 mg/dl
Time frame: week 48
Secondary
Safety: Number AEs and SAEs
number AEs and SAEs
Time frame: week 48
Secondary
Viral Resistance
number op patients with VIH viral load \> 50 copies/mL virological failure.
Time frame: week 48