ALternative TEnofovir Dosing in Adults With Moderate Renal Function Impairment

Study Overview
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Brief Summary
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To assess the drug concentrations of tenofovir (TDF) in HIV-infected Thai adults with moderate renal function impairment when administered at the recommended dose of 300 mg every 48 hours, and at an alternative dose of 150 mg every 24 hours.

Detailed Description
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The study is designed as a Phase I, non-randomized, open-label, pharmacokinetic study. We hypothesize that administration of tenofovir 150 mg once daily to HIV-infected Thai adults with moderate renal function impairment (CLcr between 30 to <50 mL/min) will provide comparable drug exposure to the current recommended dose of 300 mg every 48 hours. Confirmed HIV-positive subjects receiving tenofovir (TDF) 300 mg, every 48 hours, as part of an NNRTI-based or lopinavir/ritonavir (LPV/r)-based HAART regimen will be proposed to participate. Subjects meeting the required criteria will be enrolled into one of 2 groups depending on their HAART regimen: . Group 1: Subjects receiving tenofovir 300 mg, every 48 hours, in combination with lamivudine and an NNRTI,and a confirmed CLcr 30 to <50 mL/min Group 2: Subjects receiving tenofovir 300 mg, every 48 hours, in combination with lamivudine and lopinavir/ritonavir, and a confirmed CLcr 30 to <50 mL/min The study procedures are identical for both groups. All subjects enrolled will have two study visits. At the first visit, a 48-hour pharmacokinetic evaluation will be performed. Immediately following completion of the PK sampling, the tenofovir dose will be changed to 150 mg, once daily. Two weeks later, at the second visit, a 24-hour pharmacokinetic evaluation will be performed. Following completion of the second PK sampling the tenofovir dose will be changed back to 300 mg every 48 hours. At this time the subjects has reach the end of the study.

Official Title
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Tenofovir Pharmacokinetics in HIV-infected Thai Adults With Moderate Renal Function Impairment Receiving Either a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based or Lopinavir/Ritonavir-based Antiretroviral Therapy

Conditions
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HIV

Intervention / Treatment
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* Other: Tenofovir Dose Adjustment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >18 years old provided written informed consent receiving the tenofovir tablet formulation from the Thai Government Pharmaceutical Organization (GPO) for at least 4 weeks before enrollment documentation of confirmed HIV-1 infection (documented by two serology tests obtained at two different dates) Confirmed Creatinine clearance result between 30 to <50 mL/min [confirmed defined as two CLcr determinations calculated using the Cockcroft-Gault equation within two weeks of each other, within 1 month prior to entry] received tenofovir 300 mg, every 48 hours for at least 2 weeks prior to entry, in combination with 3TC plus NNRTI, or 3TC plus lopinavir/ritonavir a HIV-1 RNA viral load < 50 copies/mL within 6 months prior to entry Exclusion Criteria: Concomitant use of a atazanavir, didanosine Pregnant Any of the following laboratory tests within 30 days prior to study entry classified as ≥ Grade 3 (see DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0 [Dec. 2004], Clarification August, 2009): neutrophil count, hemoglobin, platelets, AST, or ALT HBs-antigen positive Any clinically significant diseases (other than HIV-1 infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise participation in this study concurrent participation to any other clinical trial without prior agreement of the two study teams

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenofovir-containing HAART<br> | Other: Tenofovir Dose Adjustment<br>* In subjects with a confirmed CLcr 30 to <50 mL/min, switch tenofovir 300 mg every 48 hours, to 150 mg once daily for 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tenofovir plasma area-under the concentration time curve (AUC) | For each patient, ratios of AUC0-last of q24h versus q48h will be calculated. Geometric mean ratios (GMRs) with 90% CI will be calculated after log-transformation of within patient ratios. | Study Entry and Day 14 |