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Antiretroviral Treatment OutcomesTOASTNCT01387022

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

A study testing Tenofovir, lamivudine and efavirenz in people with Antiretroviral Treatment Outcomes, run by Centre for the AIDS Programme of Research in South Africa at 1 site in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women onlyHealthy volunteers can take part
Conditions the study is for
Antiretroviral Treatment Outcomes
What is being tested?
Tenofovir, lamivudine and efavirenz
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
1 siteSouth Africa
Study dates
Jun 2011to Nov 2014
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

South Africa1 site
  • CAPRISA

    Durban, KwaZulu-Natal, 4000

Other trials in South Africa

About this study

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

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.

Read more

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.

Read the 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.
Being tested
Tenofovir, lamivudine and efavirenz
Keywords
Antiretroviral treatment, Tenofovir, Drug resistance, Treatment outcome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tenofovir, lamivudine and efavirenzDrug

    Tenofovir, 300mg daily, lifelong Lamivudine, 300mg daily, lifelong Efavirenz, 600mg daily, lifelong

Study groups in NCT01387022
Study groupRoleWhat they receive
Tenofovir, lamivudine and efavirenzExperimentalNot described
Receives: Drug: Tenofovir, lamivudine and efavirenz
Zidovudine, lamivudine and efavirenzActive comparatorNot described
Receives: Drug: Tenofovir, lamivudine and efavirenz

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 12 months post ART intiation or until time of death

Secondary outcomes (5)
  1. Change in CD4+ Cell Count From Randomisation to 12 Months Post-randomisation

    Difference between 12 months and randomisation CD4+ count was calculated and then summarised

    Measured: Measured at 12 months post ART initiation

  2. Tenofovir Resistance, Defined as Presence of K65R, K70E or Any of the TAMS Mutations

    Measured: From randomisation until either time of termination or time of death

  3. Reported Adverse Events With Severity Grades 3 and 4 Based on the DAIDS Toxicity Grading Tables

    Measured: From randomisation until either time of termination or time of death

  4. Cellular and Humoral Immune Responses

    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

    Measured: 3 years

  5. Genital Viral Shedding (Viral Load on Tear Flow)

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jul 2011 (estimated)
  2. Study startJun 2011
  3. Primary completionNov 2014
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01387022
Sponsor's protocol ID
CAPRISA 009
Acronym
TOAST
Status last verified
Mar 2017
First submitted
21 Jun 2011
Last updated
20 Apr 2017
Data monitoring committee
Yes

Publications

  • De Clercq E. Acyclic nucleoside phosphonates: past, present and future. Bridging chemistry to HIV, HBV, HCV, HPV, adeno-, herpes-, and poxvirus infections: the phosphonate bridge. Biochem Pharmacol. 2007 Apr 1;73(7):911-22. doi: 10.1016/j.bcp.2006.09.014. Epub 2006 Sep 19.

    PubMed 17045247
  • Schooley RT, Ruane P, Myers RA, Beall G, Lampiris H, Berger D, Chen SS, Miller MD, Isaacson E, Cheng AK; Study 902 Team. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS. 2002 Jun 14;16(9):1257-63. doi: 10.1097/00002030-200206140-00008.

    PubMed 12045491
  • Squires K, Pozniak AL, Pierone G Jr, Steinhart CR, Berger D, Bellos NC, Becker SL, Wulfsohn M, Miller MD, Toole JJ, Coakley DF, Cheng A; Study 907 Team. Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial. Ann Intern Med. 2003 Sep 2;139(5 Pt 1):313-20. doi: 10.7326/0003-4819-139-5_part_1-200309020-00006.

    PubMed 12965939
  • Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. December 1, 2009. Available from: www.aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf. Accessed 9 November 2010.

  • Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM, Miller MD, Coakley DF, Lu B, Toole JJ, Cheng AK; 903 Study Group. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004 Jul 14;292(2):191-201. doi: 10.1001/jama.292.2.191.

    PubMed 15249568
  • Rohan LC, Moncla BJ, Kunjara Na Ayudhya RP, Cost M, Huang Y, Gai F, Billitto N, Lynam JD, Pryke K, Graebing P, Hopkins N, Rooney JF, Friend D, Dezzutti CS. In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide. PLoS One. 2010 Feb 19;5(2):e9310. doi: 10.1371/journal.pone.0009310.

    PubMed 20174579
  • Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168-74. doi: 10.1126/science.1193748. Epub 2010 Jul 19.

    PubMed 20643915
  • Naicker N, Naidoo A, Werner L, Garrett N, Majola N, Asari V, Baxter C, Grobler A, Karim QA, Karim SSA. Efficacy and safety of tenofovir-containing antiretroviral therapy in women who acquired HIV while enrolled in tenofovir gel prophylaxis trials. Antivir Ther. 2017;22(4):287-293. doi: 10.3851/IMP3106. Epub 2016 Nov 4.

    PubMed 27835613

Questions about this trial

What is this clinical trial studying?

A study testing Tenofovir, lamivudine and efavirenz in people with Antiretroviral Treatment Outcomes, run by Centre for the AIDS Programme of Research in South Africa at 1 site in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Antiretroviral Treatment Failure Rate at 12 Months. (time frame: 12 months post ART intiation or until time of death). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01387022, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2017.

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