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

• Status: Completed
• Trial end date: 2017-01-18
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Diego
• Collaborators: Gilead Sciences; University at Buffalo
• Treatments: Cobicistat; Elvitegravir; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Emtricitabine tenofovir alafenamide; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir

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