PrEP Provider Toolkit
PrEP Background
Effectiveness
The majority of existing PrEP studies have focused on the use of oral F/TDF (Truvada) to prevent sexual transmission of HIV in both assigned sexes (AMAB & AFAB), regardless of sexual orientation. (9)
Grant, Anderson, P. L., McMahan, V., Liu, A., Amico, K. R., Mehrotra, M., Hosek, S., Mosquera, C., Casapia, M., Montoya, O., Buchbinder, S., Veloso, V. G., Mayer, K., Chariyalertsak, S., Bekker, L.-G., Kallas, E. G., Schechter, M., Guanira, J., Bushman, L., … Glidden, D. V. (2014). Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. The Lancet Infectious Diseases, 14(9), 820–829
https://doi.org/10.1016/S1473-3099(14)70847-3
Grant, Lama, J. R., Anderson, P. L., McMahan, V., Liu, A. Y., Vargas, L., Goicochea, P., Casapía, M., Guanira-Carranza, J. V., Ramirez-Cardich, M. E., Montoya-Herrera, O., Fernández, T., Veloso, V. G., Buchbinder, S. P., Chariyalertsak, S., Schechter, M., Bekker, L.-G., Mayer, K. H., Kallás, E. G., … Glidden, D. V. (2010). Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. The New England Journal of Medicine, 363(27), 2587–2599.
https://doi.org/10.1056/NEJMoa1011205
Baeten, Donnell, D., Mugo, N. R., Ndase, P., Thomas, K. K., Campbell, J. D., Wangisi, J., Tappero, J. W., Bukusi, E. A., Cohen, C. R., Katabira, E., Ronald, A., Tumwesigye, E., Were, E., Fife, K. H., Kiarie, J., Farquhar, C., John-Stewart, G., Kidoguchi, L., … Celum, C. (2014). Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial. The Lancet Infectious Diseases, 14(11), 1055–1064.
https://doi.org/10.1016/S1473-3099(14)70937-5
Thigpen, Kebaabetswe, P. M., Paxton, L. A., Smith, D. K., Rose, C. E., Segolodi, T. M., Henderson, F. L., Pathak, S. R., Soud, F. A., Chillag, K. L., Mutanhaurwa, R., Chirwa, L. I., Kasonde, M., Abebe, D., Buliva, E., Gvetadze, R. J., Johnson, S., Sukalac, T., Thomas, V. T., … Brooks, J. T. (2012). Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. The New England Journal of Medicine, 367(5), 423–434
https://doi.org/10.1056
To date, only one study has specifically investigated the efficacy of tenofovir disoproxil fumarate among people who inject drugs (PWIDs). (10) Like all medications, it was determined early on that the effectiveness of PrEP varies greatly with adherence.
Choopanya, Martin, M., Suntharasamai, P., Sangkum, U., Mock, P. A., Leethochawalit, M., Chiamwongpaet, S., Kitisin, P., Natrujirote, P., Kittimunkong, S., Chuachoowong, R., Gvetadze, R. J., McNicholl, J. M., Paxton, L. A., Curlin, M. E., Hendrix, C. W., & Vanichseni, S. (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 (British Edition), 381(9883), 2083–2090
https://doi.org/10.1016/S0140-6736(13)61127-7
Martin, Vanichseni, S., Suntharasamai, P., Sangkum, U., Mock, P. A., Chaipung, B., Worrajittanon, D., Leethochawalit, M., Chiamwongpaet, S., Kittimunkong, S., Gvetadze, R. J., McNicholl, J. M., Paxton, L. A., Curlin, M. E., Holtz, T. H., Samandari, T., & Choopanya, K. (2016). Factors associated with the uptake of and adherence to HIV pre-exposure prophylaxis in people who have injected drugs: an observational, open-label extension of the Bangkok Tenofovir study. The Lancet HIV, 4(2), e59–e66.
https://doi.org/10.1016/S2352-3018(16)30207-7
These initial landmark trials established that with daily adherence…
F/TDF (Truvada) reduces the risk of acquiring HIV through sex by 99% and through IVDU by 74%.
The DISCOVER trial compared F/TDF (Truvada) directly to F/TAF (Descovy). This study only included MSM/TGWSM. It was concluded that F/TAF (Descovy) is non-inferior to F/TDF (Truvada) in preventing sexual transmission among this select patient population. (11)
Mayer, Molina, J.-M., Thompson, M. A., Anderson, P. L., Mounzer, K. C., De Wet, J. J., DeJesus, E., Jessen, H., Grant, R. M., Ruane, P. J., Wong, P., Ebrahimi, R., Zhong, L., Mathias, A., Callebaut, C., Collins, S. E., Das, M., McCallister, S., Brainard, D. M., … Hare, C. B. (2020). Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. The Lancet (British Edition), 396(10246), 239–254.
https://doi.org/10.1016/S0140-6736(20)31065-5
The HIV Prevention Trials Network (HPTN) 083 and 084 were then performed in similar fashion and concluded that cabotegravir (Apretude) is superior to F/TDF (Truvada) in MSM/TGWSM and cisgender women, respectively. (12)
Landovitz, Donnell, D., Clement, M. E., Hanscom, B., Cottle, L., Coelho, L., Cabello, R., Chariyalertsak, S., Dunne, E. F., Frank, I., Gallardo-Cartagena, J. A., Gaur, A. H., Gonzales, P., Tran, H. V., Hinojosa, J. C., Kallas, E. G., Kelley, C. F., Losso, M. H., Madruga, J. V., … Sued, O. (2021). Cabotegravir for HIV prevention in cisgender men and transgender women. The New England Journal of Medicine, 385(7), 595–608.
https://doi.org/10.1056/NEJMoa2101016
Delany-Moretlwe, Hughes, J. P., Bock, P., Hunidzarira, P., Kalonji, D., Kayange, N., Makhema, J., Mandima, P., Mathew, C., Spooner, E., Mpendo, J., Mukwekwerere, P., Mgodi, N., Ntege, P. N., Nakabiito, C., Nuwagaba-Biribonwoha, H., Panchia, R., Singh, N., Farrior, J., … Marzinke, M. A. (2022). Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. The Lancet (British Edition), 399(10337), 1779–1789.
https://doi.org/10.1016/S0140-6736(22)00538-4
It is worth mentioning that the superiority of cabotegravir is primarily derived from improved patient adherence as it does not rely on the need for daily ingestion. Subset analysis does show that effectiveness was similar when F/TDF (Truvada) levels indicated proper adherence. Biochemically, they are essentially equivalent.
There has also been mounting interest and investigation of event-driven PrEP (ED-PrEP), also known as on-demand, non-daily, intermittent, or 2-1-1 PrEP. Rather than daily ingestion, ED-PrEP is a method where PrEP is taken shortly before sex and then the following two days.
ED-PrEP has only been studied using F/TDF (Truvada) to prevent the sexual acquisition of HIV among men who have sex with men (MSM). Existing studies have found that ED-PrEP is non-inferior to daily intake. (13) This type of use is not currently FDA approved in the U.S. though according to the latest CDC Guidelines, it may be considered in select patients. (14)
Centers for Disease Control and Prevention. (2021). Preexposure prophylaxis for the prevention of HIV infection in the United States – 2021 update a clinical practice guideline. U.S. Department of Health and Human Services.
https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf
Molina, Capitant, C., Spire, B., Pialoux, G., Cotte, L., Charreau, I., Tremblay, C., Le Gall, J.-M., Cua, E., Pasquet, A., Raffi, F., Pintado, C., Chidiac, C., Chas, J., Charbonneau, P., Delaugerre, C., Suzan-Monti, M., Loze, B., Fonsart, J., … Delfraissy, J.-F. (2015). On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. The New England Journal of Medicine, 373(23), 2237–2246.
https://doi.org/10.1056/NEJMoa1506273
Antoni, 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, J.-M., Aboulker, J.-P., Bajos, N., Baril, J.-G., Besnier, M., Binesse, J., … Chidiac, C. (2020). 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. The Lancet HIV, 7(2), e113–e120.
https://doi.org/10.1016/S2352-3018(19)30341-8
Take Home Points
There are many nuances to what was just discussed, which will be further detailed in the coming sections. For now, the key take-home point is that ALL forms of PrEP are highly effective in preventing HIV infections and should, at the very least, be mentioned to your patients.