Seville Cohort of People at Substantial Risk for HIV Infection on Pre-exposure Prophylaxis

Study Overview
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Brief Summary
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Pre-exposure prophylaxis (PrEP) based on tenofovir represents a considerably new preventive intervention that has shown to significantly decrease the number of HIV infections while it enables early diagnosis of HIV and other sexually transmitted diseases (STI). In Southern Spain, the target population to receive PrEP are men who have sex with men (MSM) with a history of STI and who pursue high-risk sexual practices regarding the acquisition of HIV, including an elevate number of sex partners, no or inconsistent condom use and the use of specific recreational drugs in the context of sexual activity (chemsex). Despite the benefits of PrEP use, it must be taken into consideration that risk compensations that may facilitate the acquisition of other STI may occur, including a higher implementation of risk practices and an increase in the number of partners, which is made easy as various social networks designed for this purpose are available nowadays. In order to better understand the benefit/drawback ratio, accurate data of a population using PrEP under real-life conditions, with densely scheduled follow-up and well-characterized (socio-)demographic parameters, sexual behaviour and STI are warranted.

Detailed Description
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To date, the availability of highly-active antiretroviral drugs enables an efficient and persistent suppression of HIV replication. This, on the one hand, results in a considerably higher life expectancy and quality of life among persons living with HIV (PLWH) and, on the other hand, reduces the risk of viral transmission. Based on these advances, the Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed strategies aiming to end the HIV/AIDS epidemic by including preventive tools. With the aim to prevent the acquisition of HIV infection, recommendations for the use of post-exposure prophylaxis were established, however, this strategy requires both the awareness of having been exposed to the virus, as well as the access to treatment within 72 hours after exposure, which represents important limitations when put into practice. To overcome these obstacles, pre-exposure prophylaxis has been implemented during the last decade. PrEP represents a preventive intervention that has demonstrated a significant decrease in HIV infections in a large number of randomized clinical trials and observational studies among various populations. Apart from the preventive benefits, it furthermore supports the early diagnosis of HIV and other sexually transmitted diseases (STI), leading to the World Health Organisation (WHO) to recommend its use in 2012. As a result of a complex analysis including efficacy, risks and costs, PrEP was only recommended for persons at substantial risk to get infected. Main representatives are men who have sex with men (MSM), in whom a decrease of 44%-86% in HIV infection in pilot clinical trials was observed, as well as transgender women and persons with an HIV-positive partner. Among those compliant to daily PrEP, infection rates become close to zero. Although the majority of the guidelines are based on this modality, there is evidence that MSM showing less frequent sexual activity could also benefit from on-demand PrEP. In comparison with daily PrEP, the on-demand modality encourages adherence due to its contemporaneous use with the sexual intercourse. So far, the WHO recommendations have been adapted in clinical guidelines of more than 60% of the countries worldwide, showing an increasing trend and promising results, as reported from ongoing PrEP programmes. In Spain, the use of PrEP based on tenofovir (TNF) and emtricitabine has demonstrated its benefit in a study to evaluate PrEP implementation in four Spanish settings. Subsequently, the Interministerial Commission for Medical Costs of the Spanish government approved financial support for PrEP in specific risk groups for HIV acquisition as defined by the National AIDS Plan (Plan Nacional sobre el SIDA, PNS) and since September of 2019, PrEP represents an integral part of the Andalusian Health System services. In this context, PrEP is offered as complementary preventive tool included in a package aimed to raise awareness in persons at high risk for HIV infection in order to break the chain of transmission and warrant required health care. Thus, in the setting of Seville, Andalusia (Spain), the main candidates to receive PrEP are MSM with a history of STI and high-risk sexual behaviour, including an elevated number of sex partners, no or rare use of condoms and chemsex. The latter refers to a relatively new trend in the MSM community and describes the use of specific recreational drugs, mainly metamphetamine, mephedrone, poppers or gammahydroxybutyrate (GHB)/gammabutyrolactone (GBL) in any combination or route of administration, in the context of sexual activity with one, but often multiple partners. Chemsex is associated with high-risk sex practices and the acquisition of STI. Despite the high interest in this preventive tool, real-life data on PrEP use are scarce, the sexual habits among its users are not well characterised and there is no information available for Andalusia, and especially the region of Seville, where the number of candidates for PrEP is estimated to exceed 1000 according to the Andalusian Plan against HIV/AIDS and other STI (Plan Andaluz frente al VIH/SIDA y otras ITS, PASIDA). Likewise, while the of primary HIV infections during PrEP are likely rare-to-absent, they cannot be excluded and their characteristics and clinical management are poorly studied. Additionally, in spite of the benefit of PrEP, there are various considerations regarding its use, like the development of adverse events on the short or long term in healthy people taking antiretroviral drugs, as in the case of TNF, renal function and bone density may be affected. Another major concern is the possibility of risk compensation in persons who feel less vulnerable due to the protective effect of PrEP. This could be manifested in a shift of sexual habits towards high-risk behaviour and/or an increase in the number of sex partners which can be achieved comfortably while remaining anonymous, given the social networks designed for this purpose available nowadays. Consequently, transmission of other STI, unintended pregnancies and resistance to TNF in case of primary HIV infection would be encouraged. Studies under real-life conditions including frequent and detailed monitoring are strongly needed in order to gain knowledge on the possible impact of PrEP on its users, taking into account possible changes in life style caused by the constant evolution of society and social media, like dating applications. In fact, a change in the social profile of MSM newly diagnosed with HIV infection has been reported recently in Madrid, which supports the need to improve the characterization and motorization of those participating in PrEP programmes. In order to clarify this issue, accurate data of a population using PrEP under real-life conditions, with densely scheduled follow-up and well-characterized (socio-)demographic parameters, sexual behaviour and STI are warranted.

Official Title
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A Study to Evaluate Clinical Benefits and Drawbacks of Antiretroviral Drugs as Pre-exposure Prophylaxis to Prevent HIV Infection Under Real-life Conditions Among Persons Who Pursue High-risk Sexual Practices: The Seville HIV PrEP Cohort

Conditions
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HIV Infection Primary, Hepatitis, Viral, Human, Sexually Transmitted Infections, Excluding HIV and Hepatitis

Intervention / Treatment
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* Drug: Tenofovir Disoproxil Fumarate 300 MG Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV negative as demonstrated by negative HIV serology as determined by EIA and Western-Blot. Older than 18 years. At high risk of acquiring HIV infection by sexual transmission. MSM and transsexual persons who met at least two of the following criteria during the year prior to visit: More than ten different sexual partners. Anal sexual intercourse without using a condom. Consumption of drugs in order to establish and/or maintain sexual relations without condom. Administration of post-exposition prophylaxis in various occasions de profilaxis post- exposición en varias ocasiones. At least one bacterial STI. Women who prostitute themselves with no or irregular use of a condom. -Start daily or on-demand PrEP with TDF/FTC. Give their written informed consent to participate in the cohort and its substudies. Exclusion Criteria: Glomerular filtration rate <60 ml/min. For on-demand PrEP: diagnosis of chronic hepatitis B. Allergic to TDF and/or FTC.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Men who have sex with men<br>Men who have sex with men at substantial risk for HIV infection due to high-risk sexual habits | Drug: Tenofovir Disoproxil Fumarate 300 MG Oral Tablet<br>* Pre-exposure prophylaxis with coformulated Tenofovir Disoproxil Fumarate 300mg/Emtricitabine 200mg oral QD to prevent HIV infection<br>* Other names: Emtricitabine 200 MG Oral Tablet;|
| Transgender women<br>Transgender women at substantial risk for HIV infection due to high-risk sexual habits | Drug: Tenofovir Disoproxil Fumarate 300 MG Oral Tablet<br>* Pre-exposure prophylaxis with coformulated Tenofovir Disoproxil Fumarate 300mg/Emtricitabine 200mg oral QD to prevent HIV infection<br>* Other names: Emtricitabine 200 MG Oral Tablet;|
| Sex workers<br>Sex workers at substantial risk for HIV infection due to high-risk sexual habits | Drug: Tenofovir Disoproxil Fumarate 300 MG Oral Tablet<br>* Pre-exposure prophylaxis with coformulated Tenofovir Disoproxil Fumarate 300mg/Emtricitabine 200mg oral QD to prevent HIV infection<br>* Other names: Emtricitabine 200 MG Oral Tablet;|
| HIV-uninfected people at substantial risk for HIV infection (other)<br>All HIV-uninfected people at substantial risk for HIV infection due to any other reason, including having an HIV-positive life partnerwith an HIV-positive life partner | Drug: Tenofovir Disoproxil Fumarate 300 MG Oral Tablet<br>* Pre-exposure prophylaxis with coformulated Tenofovir Disoproxil Fumarate 300mg/Emtricitabine 200mg oral QD to prevent HIV infection<br>* Other names: Emtricitabine 200 MG Oral Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline proportion of PrEP users with STI-4c at one year | Analysis of a change in the proportion of persons that present with infection by at least one of the following four common sexually transmitted pathogens (STI-4c): Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis and/or Mycoplasma genitalium. | Baseline through one year | 
| Incidence of primary HIV infection | Determination of the incidence of primary HIV infections during PrEP use | Through study completion (an average 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of PrEP users with STI other than STI-4c or HIV | Determination of the proportion of persons that present with STI other than those analysed in the primary outcome | Through study completion (an average 3 years) | 
| Number of STI | Determination of the number of STI PrEP users present with STI at the scheduled visits | Through study completion (an average 3 years) | 
| Incidences of STI other than HIV | Determination of the incidences of individual STI other than HIV | Through study completion (an average 3 years) | 
| Sexual behaviour | Determination of the number of distinct sexual risk practices conducted per person since the last study visit | Through study completion (an average 3 years) | 
| Adverse events | Determination of the rate of adverse events related to the antiretroviral drugs used for PrEP | Through study completion (an average 3 years) | 
| Adherence to PrEP | Evaluation of the adherence to PrEP modalities (daily PrEP: proportion of days PrEP was taken; on-demand PrEP: proportion of sexual intercourse with PrEP) | Through study completion (an average 3 years) | 
| Predictors of the incidence of HIV and other STI | Identification of factors associated with the incidence of HIV infection and STI other than HIV | Through study completion (an average 3 years) | 
| Predictors of a change in the proportion of STI-4c | Identification of factors associated with a change in the proportion of STI-4c | Baseline through one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, PrEP, tenofovir disoproxyl fumarate, emtricitabine, Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, human papillomavirus, men who have sex with men, ChemSex