PrEP Demonstration Project (PRELUDE Study)

NCT02206555 | Completed Phase 4 DMC

• 2 other identifiers: HEPP 140314/098
• Study Type: interventional
• Target: 327
• Locations: 1 country
• Sites: 5

Brief Summary

Significant increases in HIV diagnoses among gay and other homosexually active men, in Australia and internationally, have been observed since the late 1990s. The levels of high HIV risk sexual practices among gay men have also increased, particularly unprotected anal intercourse (UAI). Nationally, over three quarters of the new HIV infections diagnosed annually are among men who have sex with men (MSM). The proportion of heterosexual men and women among those diagnosed with HIV annually has also increased in recent years. Despite successes in some situations, HIV transmission has not been adequately reduced by the prevention methods available to those at risk, such as education, condoms, and treatment of sexually transmitted infections (STIs). The effectiveness of daily oral antiretroviral medications (ARVs) as preexposure prophylaxis of HIV (PrEP) has now been established by clinical trials in both heterosexual adults and homosexual men. Whether PrEP confers high rates of protection in real life situations and is a feasible strategy to implement still requires further investigation. Through its "HIV prevention strategy 2015: New era," NSW Health committed to consider how to most appropriately and efficiently implement PrEP in line with evidence. This commitment translated in the support to this PrEP demonstration project. This demonstration project is designed to evaluate the off-label provision of daily combination of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC, known as TRUVADA) as PrEP to a sample of sero-negative individuals at high risk for HIV infection in clinical settings in New South Wales. The project will inform policy development regarding primary HIV prevention with PrEP. This is an open-label, single-arm treatment evaluation study. All consenting and eligible HIV negative participants will receive TRUVADA prescribed for daily administration orally. At each followup visit, the following procedures will be conducted: clinical evaluations/ procedures, laboratory evaluations/ procedures, testing for HIV, STIs, hepatic and renal function, assessment for adherence to the prescribed medication, side effects, eligibility for next TRUVADA prescription, and willingness to continue on PrEP. As a study requirement, participants will be offered a self-administered assessment of behaviour, lifestyle and attitudes which will be conducted ideally within two and no more than seven days of the clinic visit in the participant's private space. Analyses will include: the feasibility of PrEP delivery, adherence to the study medication, safety and tolerability, the effects of PrEP use on behavior, and statistical analyses of the risk of HIV seroconversion.

Conditions

HIV

Keywords

HIV; prevention; prophylaxis; antiretroviral; biomedical; bio-behavioural; evaluation; demonstration study

Outcome Measures

Primary Outcomes (8)

• Time to accrual

  Time to accrual of 300 person-years of follow-up on TRUVADA. Each participant will receive TRUVADA for a maximum of 12 months, and will be followed for an additional three months after discontinuation. (Primary endpoint: feasibility of the process of PrEP delivery in health care settings in NSW)

  Approximately 18 months

• Seroconversion-free time on PrEP

  Seroconversion-free time on PrEP (Primary endpoint: feasibility of the process of PrEP delivery in health care settings in NSW)

  Approximately 18 months

• Time to TRUVADA discontinuation

  Time to TRUVADA discontinuation (primary endpoint: adherence)

  Approximately 18 months

• Prescribed doses taken

  Percentage of prescribed doses taken orally in the prescribed period (primary endpoint: adherence)

  Approximately 18 months

• Incidents of HIV seroconversion

  Incidence of HIV seroconversion among study participants during the course of their study participation and in six months following PrEP discontinuation (primary endpoint: safety and side effects)

  Approximately 24 months

• Incidents of rectal gonorrhea and chlamydia

  New rectal gonorrhoea and chlamydia infections (primary endpoint: behavioral effects of PrEP use)

  Approximately 18 months

• Serious adverse reactions

  (primary endpoint: safety and side effects)

  Approximately 18 months

• Adverse events

  Any adverse events leading to interruption or discontinuation of the study product (TRUVADA) (primary endpoint: safety and side effects)

  Approximately 18 months

Study Arms (1)

Treatment group (TRUVADA)

EXPERIMENTAL

Homosexual men and heterosexual men and women at high risk of HIV infection

Drug: emtricitabine/tenofovir disoproxil fumarate

Interventions

emtricitabine/tenofovir disoproxil fumarate DRUG

Also known as: TRUVADA, FTC/TDF

Treatment group (TRUVADA)

Eligibility Criteria

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

You may qualify if:

• HIV negative at enrollment (per algorithm provided in protocol)
• At high and ongoing risk for acquiring HIV infection (per algorithm provided in protocol)
• Aged 18 years or over
• Resident of NSW (or elsewhere in Australia if they visit NSW with sufficient frequency to allow participation)
• Medicare eligible (to have Medicare coverage for the standard-of-care services)
• Willing and able to provide informed consent
• Willing and able to take part in all required study procedures
• Proficiency in written and spoken English (necessary to complete attitude, behavioural and lifestyle surveys)

You may not qualify if:

• HIV-1 infected or has symptoms consistent with acute viral infection (If HIV positive status is not confirmed by testing, delay starting PrEP for at least one month and reconfirm negative HIV-1 status).
• Having an estimated creatinine clearance (glomerular filtration rate \[GFR\]) \<60ml/min
• Having or developing clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity (including nausea, vomiting, unusual or unexpected stomach discomfort, and weakness)
• Concurrently taking a nephrotoxic agent (e.g., high-dose non-steroidal anti-inflammatory drugs / NSAIDs)
• Allergic to tenofovir disoproxil fumarate and/or emtricitabine (based on self-report or recorded)
• Concurrently taking prescribed products containing emtricitabine or tenofovir disoproxil fumarate including ATRIPLA®, COMPLERA®, EMTRIVA, STRIBILD®, VIREAD; other drugs containing lamivudine; HEPSERA
• Mental health issues, memory loss or other cognitive impairment or intellectual disability that may compromise participant safety and/or regimen adherence
• Factors or conditions that may compromise a participant's retention in the study (incarceration, planned relocation or potential absence from NSW for a period of 3 months or longer during the course of the study)
• Unwilling to adhere to any of the required study procedures
• Currently breastfeeding

Sponsors & Collaborators

• Kirby Institute: lead

Study Sites (5)

RPA Sexual Health

Camperdown, New South Wales, 2050, Australia

Location

Holdsworth House Medical Practice

Darlinghurst, New South Wales, 2010, Australia

Location

St Vincent's Hospital HIV, Immunology and Infectious Disease Unit

Darlinghurst, New South Wales, 2010, Australia

Location

Western Sydney Sexual Health Centre

Parramatta, New South Wales, 2150, Australia

Location

Sydney Sexual Health Centre

Sydney, New South Wales, 2000, Australia

Location

Related Publications (3)

• Vaccher SJ, Marzinke MA, Templeton DJ, Haire BG, Ryder N, McNulty A, Foster R, Grulich AE, Zablotska IB; PRELUDE Study Team; NSW HIV Prevention Partnership Project. Predictors of Daily Adherence to HIV Pre-exposure Prophylaxis in Gay/Bisexual Men in the PRELUDE Demonstration Project. AIDS Behav. 2019 May;23(5):1287-1296. doi: 10.1007/s10461-018-2353-5.

  PMID: 30523489 DERIVED

• Vaccher SJ, Gianacas C, Templeton DJ, Poynten IM, Haire BG, Ooi C, Foster R, McNulty A, Grulich AE, Zablotska IB; PRELUDE Study Team. Baseline Preferences for Daily, Event-Driven, or Periodic HIV Pre-Exposure Prophylaxis among Gay and Bisexual Men in the PRELUDE Demonstration Project. Front Public Health. 2017 Dec 15;5:341. doi: 10.3389/fpubh.2017.00341. eCollection 2017.

  PMID: 29326917 DERIVED

• Vaccher S, Grulich A, McAllister J, Templeton DJ, Bloch M, McNulty A, Holden J, Poynten IM, Prestage G, Zablotska I; PRELUDE Study Team. Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration Project PRELUDE. BMJ Open. 2016 Jun 20;6(6):e012179. doi: 10.1136/bmjopen-2016-012179.

  PMID: 27324719 DERIVED

MeSH Terms

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Iryna Zablotska, MD, MPH, PhD

  Kirby Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2014
• First Posted: August 1, 2014
• Study Start: November 14, 2014
• Primary Completion: November 28, 2016
• Study Completion: December 20, 2017
• Last Updated: December 2, 2019

Record last verified: 2019-11

Locations

AU (5)