Pharmacological aspects of prophylaxis pre-exposure (prep) to HIV: a review

Authors

DOI:

https://doi.org/10.33448/rsd-v11i9.24710

Keywords:

Pharmacological aspects; HIV; Pre-exposure prophylaxis; PrEP.

Abstract

This article is a narrative review of the literature which aims to describe the main pharmacological aspects of pre-exposure prophylaxis (PrEP) to HIV. The human immunodeficiency virus (HIV) is an infection that has affected people all over the world. However, this number has decreased in recent decades, this is due to the demand for information leading to prevention and adherence to the use of PrEP PrEP is characterized as a prevention strategy that includes the daily and continuous use of antiretroviral drugs, studies show the effectiveness of the combined use of two daily antiretroviral drugs, tenofovir (TDF) and emtricitabine, commercially known as truvada. However, it is extremely important to know and discuss the pharmacological aspects of the drug, and this involves its pharmacokinetics, which in turn includes the mechanisms of absorption, distribution, metabolism and excretion of the drug, as well as other important parameters such as the half-life and elimination time of the drug, and its possible drug interactions, adverse reactions, and its mechanism of action, which is associated with the pharmacodynamic aspects of the drug.

References

Adams, L. M., & Balderson, B. H. (2016). HIV providers’ likelihood to prescribe pre-exposure prophylaxis (PrEP) for HIV prevention differs by patient type: a short report. AIDS care, 28(9), 1154-1158.

Anderson, P. L., Glidden, D. V., Liu, A., Buchbinder, S., Lama, J. R., Guanira, J. V., & iPrEx Study Team. (2012). Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Science translational medicine, 4(151), 151ra125-151ra125.

Anderson, P. L., Kiser, J. J., Gardner, E. M., Rower, J. E., Meditz, A., & Grant, R. M. (2011). Pharmacological considerations for tenofovir and emtricitabine to prevent HIV infection. Journal of antimicrobial chemotherapy, 66(2), 240-250.

Bang, L. M., & Scott, L. J. (2003). Emtricitabine. Drugs, 63(22), 2413-2424.

Bernardo, A. R. R. (2019). Enzima integrase: um alvo terapêutico validado para o desenvolvimento de fármacos antirretrovirais (Doctoral dissertation).

Baeten, J. M., Donnell, D., Ndase, P., Mugo, N. R., Campbell, J. D., Wangisi, J., & Celum, C. (2012). Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. New England Journal of Medicine, 367(5), 399-410.

Berg, T., Marcellin, P., Zoulim, F., Moller, B., Trinh, H., Chan, S., & Rousseau, F. (2010). Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection. Gastroenterology, 139(4), 1207-1217.

Best, B. M., Burchett, S., Li, H., Stek, A., Hu, C., Wang, J., & International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team. (2015). Pharmacokinetics of tenofovir during pregnancy and postpartum. HIV medicine, 16(8), 502-511.

Brasil, M. (2018). Protocolo clínico e diretrizes terapêuticas para Profilaxia Pré-Exposição (PrEP) de risco à infecção pelo HIV. Ministério da Saúde Brasil.

Buchbinder, S. P. (2018). Maximizing the benefits of HIV preexposure prophylaxis. Topics in antiviral medicine, 25(4), 138.

Chapman, T. M., McGavin, J. K., & Noble, S. (2003). Tenofovir disoproxil fumarate. Drugs, 63(15), 1597-1608.

Choopanya, K., Martin, M., Suntharasamai, P., Sangkum, U., Mock, P. A., Leethochawalit, M., & Bangkok Tenofovir Study Group. (2013). Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet, 381(9883), 2083-2090.

Colbers, A. P., Hawkins, D. A., Gingelmaier, A., Kabeya, K., Rockstroh, J. K., Wyen, C., & PANNA network. (2013). The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women. Aids, 27(5), 739-748.

Chu, I. Y. H., Ku, S. W. W., Li, C. W., Toh, H. S., Yang, C. J., Wu, K. S., & Ko, N. Y. (2020). Taiwan guideline on oral pre-exposure prophylaxis for HIV prevention–2018 update. Journal of Microbiology, Immunology and Infection, 53(1), 1-10.

Cottrell, M. L., Yang, K. H., Prince, H. M., Sykes, C., White, N., & Malone, S. (2016). A translational pharmacology approach to predicting HIV pre-exposure prophylaxis outcomes in men and women using tenofovir disoproxil fumarate+/-emtricitabine. J Infect Dis, 214(1), 55-64.

Crabtree‐Ramírez, B., Belaunzarán‐Zamudio, P. F., Cortes, C. P., Morales, M., Sued, O., Sierra‐Madero, J., & Grinsztejn, B. (2020). The HIV epidemic in Latin America: a time to reflect on the history of success and the challenges ahead. Journal of the International AIDS Society, 23(3).

de Atenção Integral, S. D. P., & de Programas Especiais, G. (2017). Boletim Epidemiológico HIV/Aids-2017.

de Atenção Integral, S. D. P., & de Programas Especiais, G. (2019). Boletim Epidemiológico HIV/Aids-2019

Eakle, R., Venter, F., & Rees, H. (2018). Pre-exposure prophylaxis (PrEP) in an era of stalled HIV prevention: Can it change the game?. Retrovirology, 15(1), 1-10.

Foster, C., Lyall, H., Olmscheid, B., Pearce, G., Zhang, S., & Gibb, D. M. (2009). Tenofovir disoproxil fumarate in pregnancy and prevention of mother‐to‐child transmission of HIV‐1: is it time to move on from zidovudine?. HIV medicine, 10(7), 397-406.

Gallant, J. E., & Moore, R. D. (2009). Renal function with use of a tenofovir-containing initial antiretroviral regimen. AIDS (London, England), 23(15), 1971.

Gonçalves, J. R. Revista JRG de Estudos Acadêmicos, ano II, (2019), vol II, n.5. ISSN: 2595-1661.

Gibas, K. M., van den Berg, P., Powell, V. E., & Krakower, D. S. (2019). Drug resistance during HIV pre-exposure prophylaxis. Drugs, 79(6), 609-619.

Gilman, A. G., Hardman, J. G., Limbird, L. E., Molinoff, P. B., & Ruddon, R. W. (1996). Goodman & Gilman: as bases farmacológicas da terapêutica. In Goodman & Gilman: as bases farmacologicas da terapeutica (pp 1637-1638).

Hendrix, C. W. (2018). HIV antiretroviral pre‐exposure prophylaxis: development challenges and pipeline promise. Clinical Pharmacology & Therapeutics, 104(6), 1082-1097.

Hillis, A., Germain, J., Hope, V., McVeigh, J., & Van Hout, M. C. (2020). Pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM): a scoping review on PrEP service delivery and programming. AIDS and Behavior, 24(11), 3056-3070.

Jayachandran, P., Garcia-Cremades, M., Vučićević, K., Bumpus, N. N., Anton, P., Hendrix, C., & Savić, R. (2021). A Mechanistic In Vivo/Ex Vivo Pharmacokinetic‐Pharmacodynamic Model of Tenofovir for HIV Prevention. CPT: pharmacometrics & systems pharmacology, 10(3), 179-187.

Kearney, B. P., Flaherty, J. F., & Shah, J. (2004). Tenofovir disoproxil fumarate. Clinical pharmacokinetics, 43(9), 595-612.

Machado, D. M., Carvalho, A. M. D. S. A., & Riera, R. (2017). Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives. Adolescent health, medicine and therapeutics, 8, 137.

Medland, N. A., Chow, E. P., Walker, R. G., Chen, M., Read, T. R., & Fairley, C. K. (2018). Incidence of renal Fanconi syndrome in patients taking antiretroviral therapy including tenofovir disoproxil fumarate. International journal of STD & AIDS, 29(3), 227-236.

Mayer, K. H., Krakower, D. S., & Boswell, S. L. (2016). Antiretroviral preexposure prophylaxis: opportunities and challenges for primary care physicians. Jama, 315(9), 867-868.

Mayer, Kenneth H. et al. Antiretroviral pre‐exposure prophylaxis implementation in the United States: a work in progress. Journal of the International AIDS Society, v. 18, p. 19980, 2015

Muller, J. T., & Al Khalili, Y. (2021). Emtricitabine. StatPearls [Internet].

Ng, H. H., Stock, H., Rausch, L., Bunin, D., Wang, A., Brill, S., & Mirsalis, J. C. (2015). Tenofovir disoproxil fumarate: toxicity, toxicokinetics, and toxicogenomics analysis after 13 weeks of oral administration in mice. International journal of toxicology, 34(1), 4-10.

Mugwanya, K. K., & Baeten, J. M. (2016). Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention. Expert opinion on drug safety, 15(2), 265-273.

National Center for Biotechnology Information (2021). PubChem Annotation Record for Tenofovir Disoproxil Fumarate, Source: Hazardous Substances Data Bank (HSDB). Retrieved December 8, 2021

Özdener, A. E., Park, T. E., Kalabalik, J., & Gupta, R. (2017). The future of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection. Expert review of anti-infective therapy, 15(5), 467-481.

Riddell, J., Amico, K. R., & Mayer, K. H. (2018). HIV preexposure prophylaxis: a review. Jama, 319(12), 1261-1268.

Saravolatz, L. D., & Saag, M. S. (2006). Emtricitabine, a new antiretroviral agent with activity against HIV and hepatitis B virus. Clinical infectious diseases, 42(1), 126-131.

Saag, M. S., Benson, C. A., Gandhi, R. T., Hoy, J. F., Landovitz, R. J., Mugavero, M. J., & Volberding, P. A. (2018). Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society–USA Panel. Jama, 320(4), 379-396.

Stek, A. M., Best, B. M., Luo, W., Capparelli, E., Burchett, S., Hu, C., & Mirochnick, M. (2012). Effect of pregnancy on emtricitabine pharmacokinetics. HIV medicine, 13(4), 226-235.

Stevens, R. C., Blum, M. R., Rousseau, F. S., & Kearney, B. P. (2004). Intracellular pharmacology of emtricitabine and tenofovir. Clinical infectious diseases, 39(6), 877-878.

Tao, X., Lu, Y., Zhou, Y., Zhang, L., & Chen, Y. (2020). Efficacy and safety of the regimens containing tenofovir alafenamide versus tenofovir disoproxil fumarate in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection: A meta-analysis of randomized controlled trials. International Journal of Infectious Diseases, 93, 108-117.

Thigpen, M. C., Kebaabetswe, P. M., Paxton, L. A., Smith, D. K., Rose, C. E., Segolodi, T. M., & Brooks, J. T. (2012). Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. New England Journal of Medicine, 367(5), 423-434.

Touger, R., & Wood, B. R. (2019). A review of telehealth innovations for HIV pre-exposure prophylaxis (PrEP). Current HIV/AIDS Reports, 16(1), 113-119.

Trang, T. P., Dong, B. J., Kojima, N., & Klausner, J. D. (2016). Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection. Expert opinion on drug safety, 15(9), 1287-1294.

Tetteh, R. A., Yankey, B. A., Nartey, E. T., Lartey, M., Leufkens, H. G., & Dodoo, A. N. (2017). Pre-exposure prophylaxis for HIV prevention: safety concerns. Drug safety, 40(4), 273-283.

Unaids. (2015). Oral pre‐exposure prophylaxis: putting a new choice in context.

Von Kleist, M., Garcia-Lerma, G., Liu, A., & Anderson, P. L. (2020). Pharmacokinetics and Pharmacodynamics of Pre-Exposure Prophylaxis Against HIV. Frontiers in Pharmacology, 11, 1288.

Wang, L. H., Begley, J., St. Claire III, R. L., Harris, J., Wakeford, C., & Rousseau, F. S. (2004). Pharmacokinetic and pharmacodynamic characteristics of emtricitabine support its once daily dosing for the treatment of HIV infection. AIDS Research & Human Retroviruses, 20(11), 1173-1182.

Wassner, C., Bradley, N., & Lee, Y. (2020). A Review and clinical understanding of tenofovir: tenofovir disoproxil fumarate versus tenofovir alafenamide. Journal of the International Association of Providers of AIDS Care (JIAPAC), 19, 2325958220919231.

World Health Organization. (2010). Report of a consultation: preparing for pre-exposure prophylaxis (PrEP) results: from research to implementation.

World Health Organization. (2017). WHO implementation tool for pre-exposure prophylaxis (PrEP) of HIV infection: module 1: clinical (No. WHO/HIV/2017.17). World Health Organization.

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Published

05/07/2022

How to Cite

PAIVA, E. B. C. .; SILVEIRA, C. R. da .; KOSMISCKY, I. de O. .; GOMES , C. da C.; BARROS, S. D. G. .; FARIAS, R. A. da C. .; SALDANHA, Z. de O. .; GOMES, A. R. Q. .; COELHO, C. S. do C. .; CARTÁGENES, S. de C. Pharmacological aspects of prophylaxis pre-exposure (prep) to HIV: a review. Research, Society and Development, [S. l.], v. 11, n. 9, p. e15511924710, 2022. DOI: 10.33448/rsd-v11i9.24710. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/24710. Acesso em: 19 apr. 2024.

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Vol. 11 No. 9

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Review Article

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Copyright (c) 2022 Edson Bruno Campos Paiva; Caroline Rocha da Silveira; Isis de Oliveira Kosmiscky; Cleiton da Costa Gomes ; Samantha Daniely Gomes Barros; Roselígia Antônia da Costa Farias; Zélia de Oliveira Saldanha; Antônio Rafael Quadros Gomes; Cybelle Silva do Couto Coelho; Sabrina de Carvalho Cartágenes

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