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

March 23, 2017 updated by: Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Purpose:

To determine whether prophylactic exposure to tenofovir gel alters the therapeutic response to a tenofovir containing antiretroviral regimen

Study design:

Open label, two-arm, randomised controlled trial

Study population:

Women who become infected with HIV while participating in the CAPRISA 004 and CAPRISA 008 trials. There are 3 study populations:

Study population 1:

HIV positive women from the CAPRISA 004 tenofovir gel arm and HIV positive women from the clinical trial tenofovir gel provision arm of CAPRISA 008

Study population 2:

HIV positive women in the placebo arm of CAPRISA 004

Study population 3:

HIV positive women from the family planning service arm of CAPRISA 008

Study sites:

CAPRISA eThekwini and CAPRISA Vulindlela clinics.

Study duration:

3 years

Study intervention:

Enrolled women will be initiated on their assigned antiretroviral therapy regimen when they reach any of the following criteria:

  • reach a CD4+ count of less than 350 cell/mm3
  • acquire an AIDS defining illness
  • become pregnant - women in any of the three study populations who become pregnant during follow-up will be initiated on their assigned treatment regimen, as appropriate, for prevention of mother-to-child transmission of HIV.

At enrolment women in each of the three study populations will be assigned randomly to one of the two following antiretroviral regimens Intervention Arm: Tenofovir, lamivudine and efavirenz Control arm: Zidovudine, lamivudine and efavirenz

Sample size: The projected sample size is 90 women. The number of women in each stratum is as follows:

Study population 1: n = 40 Study population 2: n = 30 Study population 3: n = 20

Primary endpoint:

The primary endpoint is the antiretroviral treatment failure rate at 12 months. Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death

Secondary Endpoints:

  1. Change in CD4+ cell count from the earliest post-infection timepoint to the time of randomisation to 12, 24 and 36 months post-randomisation
  2. Tenofovir resistance, defined as presence of K65R, K70E or any of the TAMS mutations.
  3. Reported adverse events with severity grades 3 and 4 based on the DAIDS toxicity grading tables
  4. Cellular and humoral immune responses
  5. Genital viral shedding (viral load on tear flow) Ancillary Endpoint Mother-to-child HIV transmission rates as determined by PCR on infant at 6 weeks.

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • KwaZulu-Natal
      • Durban, KwaZulu-Natal, South Africa, 4000
        • CAPRISA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Antiretroviral Treatment Failure Rate at 12 Months.
Time Frame: 12 months post ART intiation or until time of death
Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death
12 months post ART intiation or until time of death

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in CD4+ Cell Count From Randomisation to 12 Months Post-randomisation
Time Frame: Measured at 12 months post ART initiation
Difference between 12 months and randomisation CD4+ count was calculated and then summarised
Measured at 12 months post ART initiation
Tenofovir Resistance, Defined as Presence of K65R, K70E or Any of the TAMS Mutations
Time Frame: From randomisation until either time of termination or time of death
From randomisation until either time of termination or time of death
Reported Adverse Events With Severity Grades 3 and 4 Based on the DAIDS Toxicity Grading Tables
Time Frame: From randomisation until either time of termination or time of death
From randomisation until either time of termination or time of death
Cellular and Humoral Immune Responses
Time Frame: 3 years
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
3 years
Genital Viral Shedding (Viral Load on Tear Flow)
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

June 21, 2011

First Submitted That Met QC Criteria

June 30, 2011

First Posted (Estimate)

July 1, 2011

Study Record Updates

Last Update Posted (Actual)

April 20, 2017

Last Update Submitted That Met QC Criteria

March 23, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAPRISA 009

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Antiretroviral Treatment Outcomes

Clinical Trials on Tenofovir, lamivudine and efavirenz

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Turkmenistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe