ALternative TEnofovir Dosing in Adults With Moderate Renal Function Impairment (ALTER)

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

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Other: Tenofovir Dose Adjustment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • HIV-NAT
  • Chiang Mai, Thailand
    • Nakornping Hospital
  • Chonburi, Thailand, 20000
    • Chonburi Hospital
  • Phayao, Thailand, 56000
    • Phayao Hospital
  • Chiang Mai
    • Sanpatong, Chiang Mai, Thailand, 20120
      • Sanpatong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenofovir-containing HAART	Other: Tenofovir Dose Adjustment; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut de Recherche pour le Developpement
• Collaborators: Chiang Mai University; The Government Pharmaceutical Organization
• Investigators: Principal Investigator: Tim R Cressey, PhD, PHPT / Chiang Mai University / IRD

Publications and helpful links

General Publications

• Cressey TR, Avihingsanon A, Halue G, Leenasirimakul P, Sukrakanchana PO, Tawon Y, Jaisieng N, Jourdain G, Podany AT, Fletcher CV, Klinbuayaem V, Bowonwatanuwong C. Plasma and Intracellular Pharmacokinetics of Tenofovir Disoproxil Fumarate 300 mg Every 48 Hours vs 150 mg Once Daily in HIV-Infected Adults With Moderate Renal Function Impairment. Clin Infect Dis. 2015 Aug 15;61(4):633-9. doi: 10.1093/cid/civ346. Epub 2015 Apr 28.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: August 17, 2012
• First Submitted That Met QC Criteria: August 21, 2012
• First Posted (Estimated): August 24, 2012

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 29, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: ALTER