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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)

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ClinicalTrials.gov Identifier: NCT01387022
Recruitment Status : Completed
First Posted : July 1, 2011
Results First Posted : March 20, 2017
Last Update Posted : April 20, 2017
Sponsor:
Information provided by (Responsible Party):
Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa

Tracking Information
First Submitted Date  ICMJE June 21, 2011
First Posted Date  ICMJE July 1, 2011
Results First Submitted Date  ICMJE January 30, 2017
Results First Posted Date  ICMJE March 20, 2017
Last Update Posted Date April 20, 2017
Study Start Date  ICMJE June 2011
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: June 30, 2011)
The Antiretroviral Treatment Failure Rate at 12 Months. [ Time Frame: 12 months post enrollment ]
Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death
Change History Complete list of historical versions of study NCT01387022 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2017)
  • 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
  • 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 ]
  • 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 ]
  • 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
  • Genital Viral Shedding (Viral Load on Tear Flow) [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2011)
  • 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 ]
  • 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) ]
  • 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 ]
  • 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
  • Genital Viral Shedding (Viral Load on Tear Flow) [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial to Assess the Impact of PrEP to Tenofovir Gel on the Efficacy of Tenofovir-containing ART on Viral Suppression
Official Title  ICMJE 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
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Antiretroviral Treatment Outcomes
Intervention  ICMJE Drug: Tenofovir, lamivudine and efavirenz
Tenofovir, 300mg daily, lifelong Lamivudine, 300mg daily, lifelong Efavirenz, 600mg daily, lifelong
Study Arms  ICMJE
  • Experimental: Tenofovir, lamivudine and efavirenz
    Intervention: Drug: Tenofovir, lamivudine and efavirenz
  • Active Comparator: Zidovudine, lamivudine and efavirenz
    Intervention: Drug: Tenofovir, lamivudine and efavirenz
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 3, 2015)
59
Original Estimated Enrollment  ICMJE
 (submitted: June 30, 2011)
90
Actual Study Completion Date  ICMJE November 2014
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01387022
Other Study ID Numbers  ICMJE CAPRISA 009
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa
Study Sponsor  ICMJE Centre for the AIDS Programme of Research in South Africa
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nivashnee Naicker, MBChB Centre for the AIDS Programme of Research in South Africa
PRS Account Centre for the AIDS Programme of Research in South Africa
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP