Clinical Trial to Evaluate the Efficacy, Pharmacokinetics (PK) Interactions and Safety of Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in HIV-1-Infected Solid Organ Transplant Patients

Study Overview
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Brief Summary
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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.

Official Title
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Pilot Single-Arm Clinical Trial to Evaluate the Efficacy, PK Interactions and Safety of Dolutegravir Plus 2 NRTIs in HIV-1-Infected Solid Organ Transplant Patients

Conditions
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HIV-1-infection, Solid Organ Transplant

Intervention / Treatment
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* Drug: Lamivudine 300 MG
* Drug: Abacavir 600 MG
* Drug: Dolutegravir 50 mg
* Drug: Tenofovir Disoproxil 245Mg Tablet
* Drug: Emtricitabine 200 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV patients >18 years old who provide signed and dated informed consent; Males and females; SOT recipients (heart, liver or kidney); On stable antiretroviral therapy (ART) for ≥6 months preceding the screening visit; Plasma HIV RNA <50 cop/ml for 12 months (2 tests separated by at least 12 months with no viral load >50 between determinations); Absence of major reverse transcriptase or integrase gene mutations affecting study drug efficacy by proviral DNA sequencing Exclusion Criteria: HIV patients who have stopped ART due to virological failure; HIV patients who require treatment with DTG contraindicated medications; History or presence of an allergy or intolerance to the study drug; Active opportunistic infection; Neoplasms requiring chemotherapy. Pregnancy or breast feeding or planned pregnancy during the study period Any other contraindication to study drugs.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV-1-infected solid organ transplant patients 1<br>The patient or donor is not a carrier of genetic characteristics that predispose to a severe allergy to Abacavir or the patient is not a carrier of the hepatitis B virus. treatment 48 weeks | Drug: Lamivudine 300 MG<br>* Lamivudine 300 MG/day (48 weeks)<br>* Other names: J05AF05;Drug: Abacavir 600 MG<br>* Abacavir 600 MG/day (48 weeks)<br>* Other names: J05AF06;Drug: Dolutegravir 50 mg<br>* Dolutegravir 50 MG/day (48 weeks)<br>* Other names: J05AX12;|
| Experimental: HIV-1-infected solid organ transplant patients 2<br>The patient or donor is a carrier of genetic characteristics that predispose to a severe allergy to Abacavir or the patient is a carrier of the hepatitis B virus. treatment 48 weeks | Drug: Dolutegravir 50 mg<br>* Dolutegravir 50 MG/day (48 weeks)<br>* Other names: J05AX12;Drug: Tenofovir Disoproxil 245Mg Tablet<br>* Tenofovir 245 MG/day (48 weeks)<br>* Other names: J05AF07;Drug: Emtricitabine 200 MG<br>* Emtricitabine 200 MG/day (48 weeks)<br>* Other names: J05AF09;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic study | Peak Plasma Concentration (Cmax) mg /mL of dolutegravir. | 24-hours before the switch and 24-hours 2 weeks after switching | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral resistance | number op patients with VIH viral load > 50 copies/mL virological failure. | week 48 | 
| Changes in CD4+ cell | To assess the changes in CD4+ cell count >200 cel/mL in peripheral blood. | week 48 | 
| Lipid profile | To assess the changes in lipid profile (triglycerides) | week 48 | 
| Renal function | To assess creatinine >normal valors mg/dl> 120 mg/dl | week 48 | 
| Safety: number AEs and SAEs | number AEs and SAEs | week 48 |