Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals

Study Overview
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Brief Summary
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The project will have two tracks, one for participants who are currently taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or E/C/F/tenofovir alafenamide (E/C/F/TDF or E/C/F/TAF) single-tablet regimen* (STR) (Track A) and one for participants who will begin therapy with E/C/F/TDF or E/C/F/TAF STR during the study (Track B). Participants will take E/C/F/TDF and/or E/C/F/tenofovir alafenamide fumarate (E/C/F/TAF) STR** (if available) for 24 weeks. *Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate. **Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide fumarate.

Detailed Description
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The proposed project will be a prospective, open-label treatment trial of 14 HIV-infected adults. Participants will be enrolled in two tracks. Track A will enroll participants who have been taking E/C/F/TDF to E/C/F/TAF for at least 12 weeks. Track B will enroll participants who are not taking ART and no prior exposure to elvitegravir and no genotypic drug resistance to any component of E/C/F/TDF to E/C/F/TAF. CSF and blood will be collected twice in Track A (two on-treatment assessments) and three times in Track B (one pre-treatment, two on-treatment assessments). If possible, we plan to time assessments to bridge the transition from E/C/F/TDF to E/C/F/TAF so that all participants will ideally have one CSF collection on each regimen, enabling a paired comparison of tenofovir concentrations between the two tenofovir formulations. We estimate that 28 on-treatment CSF collections will be sufficient to provide a small-sample estimate of the distribution of elvitegravir, tenofovir and TAF into CSF.

Official Title
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Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals

Conditions
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HIV

Intervention / Treatment
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* Drug: Stribild
* Drug: Genvoya


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult men or women aged 18-60 years. Able and willing to provide informed consent. Presence of HIV-1 infection as documented by a licensed ELISA test kit and confirmed by Western blot or HIV RNA. Track A (Currently taking E/C/F/TDF or E/C/F/TAF): Taking E/C/F/TDF or E/C/F/TAF for at least 3 months prior to screening and undetectable plasma HIV-1 RNA (≤ 40 copies/mL) Track B (Currently not taking ART): Off ART for at least 3 months. Prior exposure to TDF and FTC will be allowed but subjects must not have primary genotypic drug resistance mutations to elvitegravir, tenofovir, or emtricitabine (see Exclusion Criteria) Plasma HIV-1 RNA ≥ 5,000c/mL and CD4+ T-cell count ≥200cells/mm3. Exclusion Criteria: Track B: Presence of primary drug resistance mutations for EVG, tenofovir, or emtricitabine. Use of drugs of abuse or alcohol which would interfere with adherence or completion of this study. While on-study, subjects will be instructed not to consume alcohol for 48 hours prior to pharmacokinetic sampling days. Pregnancy or breast-feeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to study entry and day of entry. Chronic, severe, or other medical conditions that, in the opinion of the investigator, would interfere with the subjects ability to participate in the protocol. Use of prohibited protocol-specified drugs, prescription or over-the-counter, within 14 days prior to study entry. Bleeding abnormality or other contraindication to lumbar puncture. Moderate or severe cognitive impairment by history or based on Montreal Cognitive Assessment. Hepatitis B surface antigen (HBsAg) positive (Positive anti-HBs antibody and negative HBsAg results are acceptable) Hepatitis C antibody (HCV Ab) positive Laboratory parameters documented within 21 days prior to study entry that would increase the risk for adverse events: Hemoglobin < 12.5 g/dL for men; < 11.5 g/dL for women; Platelet count < 100,000 platelets/mm3; AST (SGOT) or ALT (SGPT) > 1.5 x the upper limit of normal (ULN); Estimated GFR<70 ml/min Weight less than 50 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 |
| --- | --- |
| Other: Stribild Arm<br>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK. | Drug: Stribild<br>* To be administered orally, once daily with food.<br>* Other names: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate;Drug: Genvoya<br>* To be administered orally, once daily with food.<br>* Other names: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide;|
| Other: Genvoya Arm<br>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK. | Drug: Genvoya<br>* To be administered orally, once daily with food.<br>* Other names: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide;|
| Other: Untreated Arm<br>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK. | Drug: Stribild<br>* To be administered orally, once daily with food.<br>* Other names: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate;Drug: Genvoya<br>* To be administered orally, once daily with food.<br>* Other names: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline |  | Baseline | 
| Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24 |  | Week 24 | 
| Concentration of Tenofovir in Cerebrospinal Fluid at Baseline |  | Baseline | 
| Concentration of Tenofovir in Cerebrospinal Fluid at Week 24 |  | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Stribild, Genvoya, elvitegravir, Cerebrospinal Fluid