Clinical Trials

MainTitle

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

This study has been completed
Sponsor
Centre for the AIDS Programme of Research in South Africa


Information provided by (Responsible Party)
Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa

ClinicalTrials.gov Identifier
NCT01387022

First received: June 21, 2011
Last updated: March 23, 2017
Last Verified: March 2017
History of Changes
Purpose

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
Intervention Model: Parallel Assignment
Masking: None (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

Further study details as provided by Dr Salim S Abdool Karim, 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 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
Secondary Outcome Measures:
  • 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 ]

Enrollment: 59
Study Start Date: June 2011
Study Completion Date: November 2014
Primary Completion Date: November 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

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes 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

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

More Information


Responsible Party: Dr Salim S Abdool Karim, Director, Centre for the AIDS Programme of Research in South Africa  
ClinicalTrials.gov Identifier: NCT01387022   History of Changes  
Other Study ID Numbers: CAPRISA 009  
Study First Received: June 21, 2011  
Last Updated: March 23, 2017  

Keywords provided by Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa:

Antiretroviral treatment
Tenofovir
Drug resistance
Treatment outcome

Additional relevant MeSH terms:
Tenofovir
Lamivudine
Efavirenz

ClinicalTrials.gov processed this data on July 22, 2019
This information is provided by ClinicalTrials.gov.