elvitegravir (evg) cerebrospinal fluid (csf) pharmacokinetics in hiv-infected individuals

Conditions: HIV

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.

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

Keywords: stribild genvoya elvitegravir cerebrospinal fluid hiv