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

NCT01387022 | Completed Results DMC

• 1 other identifier: CAPRISA 009
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Antiretroviral Treatment Outcomes

Keywords

Antiretroviral treatment; Tenofovir; Drug resistance; Treatment outcome

Outcome Measures

Primary Outcomes (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

  12 months post ART intiation or until time of death

Secondary Outcomes (5)

• Change in CD4+ Cell Count From Randomisation to 12 Months Post-randomisation

  Measured at 12 months post ART initiation

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

  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

  From randomisation until either time of termination or time of death

• Cellular and Humoral Immune Responses

  3 years

• Genital Viral Shedding (Viral Load on Tear Flow)

  3 years

Study Arms (2)

Tenofovir, lamivudine and efavirenz

EXPERIMENTAL

Drug: Tenofovir, lamivudine and efavirenz

Zidovudine, lamivudine and efavirenz

ACTIVE COMPARATOR

Drug: Tenofovir, lamivudine and efavirenz

Interventions

Tenofovir, lamivudine and efavirenz DRUG

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

Tenofovir, lamivudine and efavirenz; Zidovudine, lamivudine and efavirenz

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre for the AIDS Programme of Research in South Africa: lead

Study Sites (1)

CAPRISA

Durban, KwaZulu-Natal, 4000, South Africa

Location

Related Publications (8)

• 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.

  PMID: 17045247 BACKGROUND

• 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.

  PMID: 12045491 BACKGROUND

• 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.

  PMID: 12965939 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 15249568 BACKGROUND

• 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.

  PMID: 20174579 BACKGROUND

• 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.

  PMID: 20643915 BACKGROUND

• 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.

  PMID: 27835613 DERIVED

MeSH Terms

Interventions

Tenofovir; Lamivudine; efavirenz

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Limitations and Caveats

The main limitation of the study was the small sample size. The eligible pool of participants was dependent on two other tenofovir gel trials, one of which experienced long delay in starting.

Results Point of Contact

• Title: Head of Statistics and Data Management
• Organization: CAPRISA

nonhlanhla.yende@caprisa.org

+27 31 260 4392

Study Officials

• Nivashnee Naicker, MBChB

  Centre for the AIDS Programme of Research in South Africa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: June 21, 2011
• First Posted: July 1, 2011
• Study Start: June 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 20, 2017
• Results First Posted: March 20, 2017

Record last verified: 2017-03

Locations

ZA (1)