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Trial to Assess the Impact of PrEP to Tenofovir Gel on the Efficacy of Tenofovir-containing ART on Viral Suppression (TOAST)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Centre for the AIDS Programme of Research in South Africa
ClinicalTrials.gov Identifier:
NCT01387022
First received: June 21, 2011
Last updated: June 30, 2011
Last verified: June 2011
  Purpose

The HIV/AIDS pandemic remains among the investigators greatest public health challenges. In the absence of an effective vaccine, focus has shifted to other prevention strategies such as pre-exposure prophylaxis. Tenofovir, with potent activity against retroviruses [1], was developed for oral use as Viread®, which is widely used for HIV treatment. The efficacy of Viread® has been demonstrated in treatment-experienced and naïve patients [2,3]. In antiretroviral-naive patients, the combination of tenofovir with lamivudine and efavirenz has been classified as a preferred regimen in the Department of Health and Human Services treatment guidelines[4], and has been adopted by the South African Department of health as the first line regimen in treatment-naïve HIV infected patients since April 2010. The durability of antiviral response, favourable resistance profile, once daily dosing, and excellent long term safety profile of tenofovir [5], makes this drug an attractive option in both treatment and prevention regimens and its long half-life [6], made it an ideal choice as the first antiretroviral drug to be formulated as a microbicide gel.

The CAPRISA 004 study conducted in South Africa which tested the effectiveness and safety of 1% tenofovir gel showed that the use of tenofovir in a gel formulation reduced HIV acquisition by 39% overall, and by 54% in women with high gel adherence [7]. There have been concerns raised regarding the use of tenofovir in both PrEP and treatment regimens due to the potential for selection of viral mutations and development of resistance in patients who have become HIV-infected while on PrEP.

There have been no studies conducted to determine whether using tenofovir in pre-exposure prophylaxis affects treatment outcomes in patients who later use tenofovir, which is part of the first line ART of South Africa.

This study aims to determine whether prophylactic exposure to tenofovir gel alters the therapeutic response to a tenofovir containing antiretroviral regimen.


Condition Intervention
Antiretroviral Treatment Outcomes
Drug: Tenofovir, lamivudine and efavirenz

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label Randomized Controlled Trial to Assess the Impact of Prophylactic Exposure to Tenofovir Gel on the Efficacy of Subsequent Tenofovir-containing Antiretroviral Therapy on Viral Suppression

Resource links provided by NLM:


Further study details as provided by Centre for the AIDS Programme of Research in South Africa:

Primary Outcome Measures:
  • The antiretroviral treatment failure rate at 12 months. [ Time Frame: 12 months post enrollment ] [ Designated as safety issue: No ]
    Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death


Secondary Outcome Measures:
  • Change in CD4+ cell count from the earliest post-infection timepoint to the time of randomisation to 12, 24 and 36 months post-randomisation [ Time Frame: Measured at 12, 24 and 36 months post-randomisation ] [ Designated as safety issue: No ]
  • Tenofovir resistance, defined as presence of K65R, K70E or any of the TAMS mutations [ Time Frame: Testing to be done after 36 months (post study completion) ] [ Designated as safety issue: No ]
  • Reported adverse events with severity grades 3 and 4 based on the DAIDS toxicity grading tables [ Time Frame: Reportable during the 3 year follow-up period ] [ Designated as safety issue: Yes ]
  • Cellular and humoral immune responses [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    We will assess whether exposure to tenofovir gel at the time of HIV acquisition alters the subsequent humoral and cellular immune responses following antiretroviral treatment initiation

  • Genital viral shedding (viral load on tear flow) [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: June 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tenofovir, lamivudine and efavirenz Drug: Tenofovir, lamivudine and efavirenz
Tenofovir, 300mg daily, lifelong Lamivudine, 300mg daily, lifelong Efavirenz, 600mg daily, lifelong
Active Comparator: Zidovudine, lamivudine and efavirenz Drug: Tenofovir, lamivudine and efavirenz
Tenofovir, 300mg daily, lifelong Lamivudine, 300mg daily, lifelong Efavirenz, 600mg daily, lifelong

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Previously enrolled in the CAPRISA 004 or CAPRISA 008 study - placebo or active arms
  • Able and willing to provide informed consent to be screened for, and to enrol in, the study
  • Able and willing to provide adequate locator information for study retention purposes
  • Confirmed HIV infection in the CAPRISA 004 or 008 trial
  • Agree to adhere to study visits and procedures

Exclusion Criteria:

  • Currently on antiretroviral therapy (including PMTCT prophylaxis)
  • Has any other condition that, based on the opinion of the Investigator or designee, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01387022

Locations
South Africa
CAPRISA
Durban, KwaZulu-Natal, South Africa, 4000
Sponsors and Collaborators
Centre for the AIDS Programme of Research in South Africa
Investigators
Principal Investigator: Nivashnee Naicker, MBChB Centre for the AIDS Programme of Research in South Africa
  More Information

Publications:

Responsible Party: Dr. Nivashnee Naicker, CAPRISA
ClinicalTrials.gov Identifier: NCT01387022     History of Changes
Other Study ID Numbers: CAPRISA 009
Study First Received: June 21, 2011
Last Updated: June 30, 2011
Health Authority: South Africa: University of KwaZulu-Natal Biomedical Research Ethics Committee

Keywords provided by Centre for the AIDS Programme of Research in South Africa:
Antiretroviral treatment
Tenofovir
Drug resistance
Treatment outcome

Additional relevant MeSH terms:
Efavirenz
Lamivudine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014