Clinical trial NCT02251236: Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals
Official title: Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: Stribild
Genvoya
elvitegravir
Cerebrospinal Fluid
HIV
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: University at Buffalo
First posted: 2014-09-29
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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:

  1. Hemoglobin \< 12.5 g/dL for men; \< 11.5 g/dL for women;
  2. Platelet count \< 100,000 platelets/mm3;
  3. AST (SGOT) or ALT (SGPT) \> 1.5 x the upper limit of normal (ULN);
  4. Estimated GFR\<70 ml/min
  5. Weight less than 50 kg

Primary outcomes:
measure: Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline
timeFrame: Baseline
measure: Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24
timeFrame: Week 24
measure: Concentration of Tenofovir in Cerebrospinal Fluid at Baseline
timeFrame: Baseline
measure: Concentration of Tenofovir in Cerebrospinal Fluid at Week 24
timeFrame: Week 24
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UC San Diego AntiViral Research Center
state: California
Study officials:
affiliation: UCSD
name: Scott Letendre, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ma Q, Ocque AJ, Morse GD, Sanders C, Burgi A, Little SJ, Letendre SL. Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid. Clin Infect Dis. 2020 Aug 14;71(4):982-988. doi: 10.1093/cid/ciz926.