PrEP Demonstration Project (PRELUDE Study)

Study Overview
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Brief Summary
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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.

Official Title
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Implementation of HIV Preexposure Prophylaxis With Antiretroviral Medications Among People at High Risk for HIV Infection: A Demonstration Project

Conditions
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HIV

Intervention / Treatment
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* Drug: emtricitabine/tenofovir disoproxil fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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 Note: Safety for infants exposed to TRUVADA during pregnancy is not fully assessed but no harm has been reported. Therefore, planning to become pregnant or currently being pregnant is not an exclusion criterion for this study. However, women who are pregnant should learn about the risks and benefits of TRUVADA to reduce the risk of acquiring HIV during their pregnancy. Site investigators will review the risks and benefits of TRUVADA and of potential HIV infection with pregnant women and women who plan to become pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group (TRUVADA)<br>Homosexual men and heterosexual men and women at high risk of HIV infection | Drug: emtricitabine/tenofovir disoproxil fumarate<br> <br> * Other names: FTC/TDF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, prevention, prophylaxis, antiretroviral, biomedical, bio-behavioural, evaluation, demonstration study