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

Hepatitis, Viral, Human Clinical Trial

— SeVIHPrEP  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05492565
• Other study ID #: SeVIHPrEP Cohort
• Secondary ID: FIS-PRE-2022-01
• Status: Enrolling by invitation
• Start date: January 1, 2020
• Est. completion date: December 31, 2030

Study information

• Verified date: September 2023
• Source: Hospitales Universitarios Virgen del Rocío
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 500
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• Hepatitis
• Hepatitis A
• Hepatitis, Viral, Human
• HIV Infection Primary
• HIV Infections
• Infections
• Sexually Transmitted Diseases

Intervention

Drug:
• Tenofovir Disoproxil Fumarate 300 MG Oral Tablet
Pre-exposure prophylaxis with coformulated Tenofovir Disoproxil Fumarate 300mg/Emtricitabine 200mg oral QD to prevent HIV infection

Locations

Country	Name	City	State
Spain	Virgen del Rocío University Hospital	Seville	Andalusia

Sponsors (2)

Lead Sponsor	Collaborator
Hospitales Universitarios Virgen del Rocío	Instituto de Biomedicina de Sevilla

Country where clinical trial is conducted

Spain, 

References & Publications (19)

Adams JL, Shelley K, Nicol MR. Review of Real-World Implementation Data on Emtricitabine-Tenofovir Disoproxil Fumarate as HIV Pre-exposure Prophylaxis in the United States. Pharmacotherapy. 2019 Apr;39(4):486-500. doi: 10.1002/phar.2240. Epub 2019 Apr 1. — View Citation

Ambrosioni J, Petit E, Liegeon G, Laguno M, Miro JM. Primary HIV-1 infection in users of pre-exposure prophylaxis. Lancet HIV. 2021 Mar;8(3):e166-e174. doi: 10.1016/S2352-3018(20)30271-X. Epub 2020 Dec 11. — View Citation

Antoni G, Tremblay C, Delaugerre C, Charreau I, Cua E, Rojas Castro D, Raffi F, Chas J, Huleux T, Spire B, Capitant C, Cotte L, Meyer L, Molina JM; ANRS IPERGAY study group. On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial. Lancet HIV. 2020 Feb;7(2):e113-e120. doi: 10.1016/S2352-3018(19)30341-8. Epub 2019 Nov 26. — View Citation

Ayerdi Aguirrebengoa O, Vera Garcia M, Arias Ramirez D, Gil Garcia N, Puerta Lopez T, Clavo Escribano P, Ballesteros Martin J, Lejarraga Canas C, Fernandez Pineiro N, Fuentes Ferrer ME, Garcia Lotero M, Hurtado Gallegos E, Raposo Utrilla M, Estrada Perez V, Del Romero Guerrero J, Rodriguez Martin C. Low use of condom and high STI incidence among men who have sex with men in PrEP programs. PLoS One. 2021 Feb 4;16(2):e0245925. doi: 10.1371/journal.pone.0245925. eCollection 2021. — View Citation

Ayerdi Aguirrebengoa O, Vera Garcia M, Puerta Lopez T, Clavo Escribano P, Ballesteros Martin J, Lejarrag Canas C, Fuentes Ferrer E, Raposo Utrilla M, Estrada Perez V, Del Romero Guerrero J, Rodriguez Martin C; Sandoval Study Group. Changes in the profile of newly HIV-diagnosed men who have sex with men, Madrid, 2014 to 2019. Euro Surveill. 2021 Nov;26(47):2001501. doi: 10.2807/1560-7917.ES.2021.26.47.2001501. — View Citation

Barreiro P. Sexually Transmitted Infections on the Rise in PrEP Users. AIDS Rev. 2018 Jan-Mar;20(1):71. — View Citation

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Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587-99. doi: 10.1056/NEJMoa1011205. Epub 2010 Nov 23. — View Citation

Guerras JM, Hoyos Miller J, Agusti C, Chanos S, Pichon F, Kuske M, Cigan B, Fuertes R, Stefanescu R, Ooms L, Casabona J, de la Fuente L, Belza MJ; Euro HIV EDAT Working Group. Association of Sexualized Drug Use Patterns with HIV/STI Transmission Risk in an Internet Sample of Men Who Have Sex with Men from Seven European Countries. Arch Sex Behav. 2021 Feb;50(2):461-477. doi: 10.1007/s10508-020-01801-z. Epub 2020 Sep 2. — View Citation

Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. Geneva: World Health Organization; 2015 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK327115/ — View Citation

Iniesta C, Coll P, Barbera MJ, Garcia Deltoro M, Camino X, Fagundez G, Diaz A, Polo R; Spanish Working Group for PrEP. Implementation of pre-exposure prophylaxis programme in Spain. Feasibility of four different delivery models. PLoS One. 2021 Feb 8;16(2):e0246129. doi: 10.1371/journal.pone.0246129. eCollection 2021. — View Citation

Maxwell S, Shahmanesh M, Gafos M. Chemsex behaviours among men who have sex with men: A systematic review of the literature. Int J Drug Policy. 2019 Jan;63:74-89. doi: 10.1016/j.drugpo.2018.11.014. Epub 2018 Dec 1. — View Citation

Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, Tremblay C, Le Gall JM, Cua E, Pasquet A, Raffi F, Pintado C, Chidiac C, Chas J, Charbonneau P, Delaugerre C, Suzan-Monti M, Loze B, Fonsart J, Peytavin G, Cheret A, Timsit J, Girard G, Lorente N, Preau M, Rooney JF, Wainberg MA, Thompson D, Rozenbaum W, Dore V, Marchand L, Simon MC, Etien N, Aboulker JP, Meyer L, Delfraissy JF; ANRS IPERGAY Study Group. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015 Dec 3;373(23):2237-46. doi: 10.1056/NEJMoa1506273. Epub 2015 Dec 1. — View Citation

Reitsema M, Hoek AJV, van der Loeff MS, Hoornenborg E, van Sighem A, Wallinga J, van Benthem B, Xiridou M. Preexposure prophylaxis for men who have sex with men in the Netherlands: impact on HIV and Neisseria gonorrhoeae transmission and cost-effectiveness. AIDS. 2020 Mar 15;34(4):621-630. doi: 10.1097/QAD.0000000000002469. — View Citation

Schaefer R, Schmidt HA, Ravasi G, Mozalevskis A, Rewari BB, Lule F, Yeboue K, Brink A, Mangadan Konath N, Sharma M, Seguy N, Hermez J, Alaama AS, Ishikawa N, Dongmo Nguimfack B, Low-Beer D, Baggaley R, Dalal S. Adoption of guidelines on and use of oral pre-exposure prophylaxis: a global summary and forecasting study. Lancet HIV. 2021 Aug;8(8):e502-e510. doi: 10.1016/S2352-3018(21)00127-2. Epub 2021 Jul 12. — View Citation

Smith DK, Grohskopf LA, Black RJ, Auerbach JD, Veronese F, Struble KA, Cheever L, Johnson M, Paxton LA, Onorato IM, Greenberg AE; U.S. Department of Health and Human Services. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR Recomm Rep. 2005 Jan 21;54(RR-2):1-20. — View Citation

Spinner CD, Boesecke C, Zink A, Jessen H, Stellbrink HJ, Rockstroh JK, Esser S. HIV pre-exposure prophylaxis (PrEP): a review of current knowledge of oral systemic HIV PrEP in humans. Infection. 2016 Apr;44(2):151-8. doi: 10.1007/s15010-015-0850-2. Epub 2015 Oct 15. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Incidence of primary HIV infection	Determination of the incidence of primary HIV infections during PrEP use	Through study completion (an average 3 years)
Secondary	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)
Secondary	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)
Secondary	Incidences of STI other than HIV	Determination of the incidences of individual STI other than HIV	Through study completion (an average 3 years)
Secondary	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)
Secondary	Adverse events	Determination of the rate of adverse events related to the antiretroviral drugs used for PrEP	Through study completion (an average 3 years)
Secondary	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)
Secondary	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)
Secondary	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

External Links

•   CDC (Centers for Disease Control and Prevention). Preexposure prophylaxis for the prevention of HIV infection in the United States - 2017 update.
•   Ministerio de Sanidad Servicios Sociales e Igualdad. Documento de consenso. Profilaxis Preexposición al VIH en España. Plan Nacional sobre el Sida. Published Online First: 2018
•   Secretaria General de Sanidad y Consumo. Acuerdos de la reunión de la Comisión Interministerial de Precios de los Medicamentos: Sesión 194 de 30 de septiembre de 2019. Apartado B. 2019.
•   United Nations Programme on HIV/AIDS 2020. 90-90-90: An ambitious treatment target to help end the AIDS epidemic. 2019