Safety Study of Once a Day ART and Opiate Substitute. (3OD)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open-label Multicenter Study to Assess the Efficacy, the Tolerability and the Adherence of a Once Daily (QD) Taken Antiretroviral Therapy (ART) Containing the NtRTI Tenofovir DF 300 mg in Combination With the Best Suitable Once a Day Regimen Being 1 NRTI Plus 1 PI or 1 NRTI Plus 1 NNRTI in HIV-1-infected IVDU- Patients With Opiate Substitution Being Either Antiretroviral-naive or With Suppressed Viral Load and Without a History of Virological Failure|
- Proportion of patients with HIV RNA < 400 and with HIV RNA < 50 copies/mL at Week 48
- Proportion of patients with HIV RNA < 400 and with HIV RNA < 50 copies/mL at Week 24
- Time to failure or ART discontinuation. Virological failure is defined as 2 consecutive measurements 4 weeks apart with viral load of HIV RNA > 400 copies/mL
- Adherence to HIV treatments (Medication Adherence Self-Report Inventory [MASRI] questionnaire, monthly evaluation through patient diary)
- Adherence to opiate substitution treatment
- Correlation of adherence to ART and HIV RNA levels
- Percentage of patients with HIV-1 RNA below limit of detection < 400 copies/mL and 50 copies/mL and adherence level > 95%, > 90%, > 85%, > 80%, > 75%, > 70%, > 50% and < 50%
- Dose adjustments for methadone
- Proportion of patients with any adverse event (AE)/serious adverse event (SAE)
- Proportion of patients with AE/SAE classified by body system
- Proportion of patients with each AE/SAE
- Distribution of intensity of each AE/SAE (the highest intensity per patient for each event will be considered)
- Distribution of relationship to study drug (the strongest relationship to study drug per patient for each event will be considered)
- Distribution of toxicity grade (the highest grade per patient for each test will be considered)
|Study Start Date:||March 2003|
|Estimated Study Completion Date:||June 2006|
Patients with a history of opiate abuse (IVDU) are not only a patient population that is frequently difficult to reach by the healthcare system, but it also exhibits specific problems in HIV-treatment (ART). These patients frequently have a chaotic lifestyle, which makes it difficult to take medications regularly. Amongst the reasons for this are housing difficulties, intoxication and substance abuse.
The introduction of opiate substitution treatment can help to provide some structure and certainty to patients. Even so IVDU patients are often started on ART later than others and have a greater tendency to have treatment interruptions and sub-optimal adherence to ART. The end result can be treatment failure and the development of drug resistance.
There is an unmet medical need for ART regimens that make adherence easier and may be suitable for co-administration with once-daily opiate substitution.
The availability of tenofovir disoproxil fumarate (DF) 300 mg offers new options in the creation of once-daily regimens with reduced potential for drug-drug-interactions. It is believed that it is now possible to construct viable once daily HIV treatment regimens for patients who have either never received prior therapy or who have no history of drug resistance. Tenofovir DF is administered as a single 300 mg tablet once daily with food for the treatment of HIV infection. This once daily dosing schedule of tenofovir DF makes it an attractive option for simplified dosing regimens in many subjects, including methadone-maintained individuals infected with HIV. Because many opiate-maintained subjects are required to have their methadone dosing directly observed in the clinic, there is considerable interest in using directly-observed therapy (DOT) in such subjects. Given that tenofovir is eliminated renally and methadone is predominantly hepatically metabolized, the potential for a pharmacokinetic interaction is low. However, other antiretroviral agents with substantial renal elimination such as didanosine and stavudine have been shown to interact pharmacokinetically with methadone. Thus, it is important to demonstrate that tenofovir DF and methadone can be administered together safely and without concern for a pharmacokinetic interaction and/or alterations in the efficacy, safety, or tolerability of methadone maintenance such that dose modifications would be required. This can also be influenced by the other products in the combination therapy.
HIV/HBV coinfection is a frequent issue in this population (> 20%). Treatment with TDF, which is active against HBV, could help to stabilize the chronic HBV infection, even in cases with Lamivudine-resistance.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00324688
|Study Director:||Thomas Mertenskoetter||Gilead Sciences|