Public health authorities are broadly promoting a strategy known as pre-exposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) transmission in the context of high-risk sexual activity and injection drug use. However, there are several limitations to this strategy that are underrecognized. This article reviews the primary literature supporting the use of PrEP and explores the unintended consequences associated with its use. Current public health messaging indicates that PrEP reduces the risk of HIV transmission during sex by 99 percent; however, this figure is based on modeling rather than study findings, and real-world efficacy may be significantly lower. PrEP has been associated with increased rates of sexually transmitted infections, risk compensation, HIV drug resistance, low adherence, and drug side effects. To make fully informed decisions, medical professionals and patients should be aware of these pitfalls. Additionally, this article explores the bioethical implications of prescribing PrEP from a Catholic perspective. Although not always morally illicit, PrEP is most often prescribed in the context of sexual activity outside of marriage between a biological male and female, placing the prescriber in cooperation with activity deemed to be immoral by the Catholic Church. While all medical professionals seeking the common good should aim to reduce the transmission of HIV, not all means are morally licit. Conscience protection for medical professionals opposed to this strategy has become increasingly relevant. Thoughtful discernment is necessary when considering PrEP.
Summary: The use of CDC material (figure 1) in this article does not imply endorsement by CDC. The material is in the public domain and available on the CDC website free of charge.
AndersonPeter L.GliddenDavid V.LiuAlbertBuchbinderSusanLamaJavier R.GuaniraJuan VicenteMcMahanVanessa, et al.2012. “Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men.” Science Translational Medicine4 (151). https://doi.org/10.1126/scitranslmed.3004006.
2.
AungEi T.FairleyChristopher K.OngJason J.ChenMarcus Y.PhillipsTiffany R.TranJulienSamraRanjitChowEric P. F.. 2023. “Incidence and Risk Factors for Early Syphilis Among Men Who Have Sex With Men in Australia, 2013–2019: A Retrospective Cohort Study.” Open Forum Infectious Diseases10 (2). https://doi.org/10.1093/ofid/ofad017.
3.
BaetenJared M.DonnellDeborahNdasePatrickMugoNelly R.CampbellJames D.WangisiJonathanTapperoJordan W., et al.2012. “Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women.” New England Journal of Medicine367 (5): 399–410. https://doi.org/10.1056/NEJMoa1108524.
BoshKarin A.HallH. IreneEasthamLauraDaskalakisDemetre C.MerminJonathan H.. 2021. “Estimated Annual Number of HIV Infections ─ United States, 1981–2019.” MMWR. Morbidity and Mortality Weekly Report70 (22): 801–6. https://doi.org/10.15585/mmwr.mm7022a1.
6.
BuchbinderSusan P.GliddenDavid V.LiuAlbert Y.McMahanVanessaGuaniraJuan V.MayerKenneth H.GoicocheaPedroGrantRobert M.. 2014. “HIV Pre-Exposure Prophylaxis in Men Who Have Sex with Men and Transgender Women: A Secondary Analysis of a Phase 3 Randomised Controlled Efficacy Trial.” The Lancet Infectious Diseases14 (6): 468–75. https://doi.org/10.1016/S1473-3099(14)70025-8.
7.
Castillo-MancillaJose R.ZhengJia-HuaRowerJoseph E.MeditzAmieGardnerEdward M.PredhommeJulieFernandezCaitlin, et al.2013. “Tenofovir, Emtricitabine, and Tenofovir Diphosphate in Dried Blood Spots for Determining Recent and Cumulative Drug Exposure.” AIDS Research and Human Retroviruses29 (2): 384–90. https://doi.org/10.1089/aid.2012.0089.
8.
Catechism of the Catholic Church. 1997. 2nd Edition. Washington, D.C.: United States Conference of Catholic Bishops.
Centers for Disease Control and Prevention. 2021. “Centers for Disease Control and Prevention: US Public Health Service: Preexposure Prophylaxis for the Prevention of HIV Infection in the United States—2021 Update: A Clinical Practice Guideline.” https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf
ChangJosephDoDuyDelgadoHectorKanimianNatalieHuynhAn. 2022. “A Retrospective Analysis of Bone Loss in Tenofovir-Emtricitabine Therapy for HIV PrEP.” International Journal of STD & AIDS33 (14): 1183–92. https://doi.org/10.1177/09564624221130129.
16.
ChessonHarrell W.PinkertonSteven D.VoigtRichardCountsGeorge W.. 2003. “HIV Infections and Associated Costs Attributable to Syphilis Coinfection Among African Americans.” American Journal of Public Health93 (6): 943–48. https://doi.org/10.2105/AJPH.93.6.943.
17.
ChoopanyaKachitMartinMichaelSuntharasamaiPravanSangkumUdomsakMockPhilip A.LeethochawalitManojChiamwongpaetSithisat, et al.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 Lancet381 (9883): 2083–90. https://doi.org/10.1016/S0140-6736(13)61127-7.
18.
DickersonMary C.JohnstonJeffDeleaThomas E.WhiteAliceAndrewsElizabeth. 1996. “The Causal Role for Genital Ulcer Disease as a Risk Factor for Transmission of Human Immunodeficiency Virus.” Sexually Transmitted Diseases23 (5): 429–40. https://doi.org/10.1097/00007435-199609000-00015.
19.
GrantRobert MAndersonPeter L.McMahanVanessaLiuAlbertAmicoK. RivetMehrotraMeghaHosekSybil, et al.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 Diseases14 (9): 820–29. https://doi.org/10.1016/S1473-3099(14)70847-3.
20.
GrantRobert M.LamaJavier R.AndersonPeter L.McMahanVanessaLiuAlbert Y.VargasLorenaGoicocheaPedro, et al.2010. “Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men.” New England Journal of Medicine363 (27): 2587–99. https://doi.org/10.1056/NEJMoa1011205.
HarawaNina T.HollowayIan W.LeibowitzArleenWeissRobertGildnerJenniferLandovitzRaphael J.PerezMario J.KulkarniSonaliRotheram-BorusMary JaneShoptawSteven. 2017. “Serious Concerns Regarding a Meta-Analysis of Preexposure Prophylaxis Use and STI Acquisition.” AIDS31 (5): 739–40. https://doi.org/10.1097/QAD.0000000000001386.
HoltMartinLeaTobyMaoLiminKolsteeJohannZablotskaIrynaDuckTimAllanBrent, et al.2018. “Community-Level Changes in Condom Use and Uptake of HIV Pre-Exposure Prophylaxis by Gay and Bisexual Men in Melbourne and Sydney, Australia: Results of Repeated Behavioural Surveillance in 2013–17.” The Lancet HIV5 (8): e448–56. https://doi.org/10.1016/S2352-3018(18)30072-9.
JourdainHugoBillioti de GageSophieDesplasDavidDray-SpiraRosemary. 2022. “Real-World Effectiveness of Pre-Exposure Prophylaxis in Men at High Risk of HIV Infection in France: A Nested Case-Control Study.” The Lancet Public Health7 (6): e529–36. https://doi.org/10.1016/S2468-2667(22)00106-2.
27.
JuusolaJessie L.BrandeauMargaret L.OwensDouglas K.BendavidEran. 2012. “The Cost-Effectiveness of Preexposure Prophylaxis for HIV Prevention in the United States in Men Who Have Sex With Men.” Annals of Internal Medicine156 (8): 541. https://doi.org/10.7326/0003-4819-156-8-201204170-00001.
28.
KojimaNoahDaveyDvora JosephKlausnerJeffrey D.. 2016. “Pre-Exposure Prophylaxis for HIV Infection and New Sexually Transmitted Infections among Men Who Have Sex with Men.” AIDS30 (14): 2251–52. https://doi.org/10.1097/QAD.0000000000001185.
29.
KumarSagarHaderxhanajLaura T.SpicknallIan H.. 2021. “Reviewing PrEP’s Effect on STI Incidence Among Men Who Have Sex with Men—Balancing Increased STI Screening and Potential Behavioral Sexual Risk Compensation.” AIDS and Behavior25 (6): 1810–18. https://doi.org/10.1007/s10461-020-03110-x.
30.
LandovitzRaphael J.LiSueEronJoseph J.GrinsztejnBeatrizDawoodHalimaLiuAlbert Y.MagnusManya, et al.2020. “Tail-Phase Safety, Tolerability, and Pharmacokinetics of Long-Acting Injectable Cabotegravir in HIV-Uninfected Adults: A Secondary Analysis of the HPTN 077 Trial.” The Lancet HIV7 (7): e472–481. https://doi.org/10.1016/S2352-3018(20)30106-5.
31.
MarrazzoJeanne M.RamjeeGitaRichardsonBarbra A.GomezKailazaridMgodiNyaradzoNairGonasagriePalaneeThesla, et al.2015. “Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women.” New England Journal of Medicine372 (6): 509–18. https://doi.org/10.1056/NEJMoa1402269.
32.
McCormackSheenaDunnDavid T.DesaiMonicaDollingDavid I.GafosMitzyGilsonRichardSullivanAnn K., et al.2016. “Pre-Exposure Prophylaxis to Prevent the Acquisition of HIV-1 Infection (PROUD): Effectiveness Results from the Pilot Phase of a Pragmatic Open-Label Randomised Trial.” The Lancet387 (10013): 53–60. https://doi.org/10.1016/S0140-6736(15)00056-2.
33.
MisraKavitaHuangJamie S.UdeaguChi-Chi N.ForgioneLisaXiaQiangTorianLucia V.. 2023. “Pre-Exposure Prophylaxis (PrEP) Use History in People with Antiretroviral Resistance at HIV Diagnosis: Findings from New York City HIV Surveillance and Partner Services, 2015-2022.” Clinical Infectious Diseases. https://doi.org/10.1093/CID/CIAD699.
34.
MoherDavidSchulzKenneth F.AltmanDouglas G.. 2001. “The CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel Group Randomized Trials.” BMC Medical Research Methodology1 (1): 2. https://doi.org/10.1186/1471-2288-1-2.
35.
MolinaJean-MichelCapitantCatherineSpireBrunoPialouxGillesCotteLaurentCharreauIsabelleTremblayCecile, et al.2015. “On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.” New England Journal of Medicine373 (23): 2237–46. https://doi.org/10.1056/NEJMoa1506273.
36.
MontañoMichalina A.DombrowskiJulia C.DasguptaSayanGoldenMatthew R.ManhartLisa E.BarbeeLindley A.DuerrAnnKhosropourChristine M.. 2019. “Differences in Sexually Transmitted Infection Risk Comparing Preexposure Prophylaxis Users and Propensity Score Matched Historical Controls in a Clinic Setting.” AIDS33 (11): 1773–80. https://doi.org/10.1097/QAD.0000000000002281.
OwensDouglas K.DavidsonKarina W.KristAlex H.BarryMichael J.CabanaMichaelCaugheyAaron B.CurrySusan J., et al.2019. “Preexposure Prophylaxis for the Prevention of HIV Infection.” JAMA321 (22): 2203. https://doi.org/10.1001/jama.2019.6390.
ParikhUrvi M.KossCatherine A.MellorsJohn W.. 2022. “Long-Acting Injectable Cabotegravir for HIV Prevention: What Do We Know and Need to Know About the Risks and Consequences of Cabotegravir Resistance?” Current HIV/AIDS Reports19 (5): 384–93. https://doi.org/10.1007/s11904-022-00616-y.
SidebottomDavidEkströmAnna MiaStrömdahlSusanne. 2018. “A Systematic Review of Adherence to Oral Pre-Exposure Prophylaxis for HIV – How Can We Improve Uptake and Adherence?” BMC Infectious Diseases18 (1): 581. https://doi.org/10.1186/s12879-018-3463-4.
44.
ThigpenMichael C.KebaabetswePoloko M.PaxtonLynn A.SmithDawn K.RoseCharles E.SegolodiTebogo M.HendersonFaith L., et al.2012. “Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in Botswana.” New England Journal of Medicine367 (5): 423–34. https://doi.org/10.1056/NEJMoa1110711.
45.
TraegerMichael W.CornelisseVincent J.AsselinJasonPriceBrianRothNorman J.WillcoxJeffTeeBan Kiem, et al.2019. “Association of HIV Preexposure Prophylaxis With Incidence of Sexually Transmitted Infections Among Individuals at High Risk of HIV Infection.” JAMA321 (14): 1380. https://doi.org/10.1001/jama.2019.2947.
46.
TraegerMichael W.SchroederSophia E.WrightEdwina J.HellardMargaret E.CornelisseVincent J.DoyleJoseph S.StoovéMark A.. 2018. “Effects of Pre-Exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection on Sexual Risk Behavior in Men Who Have Sex With Men: A Systematic Review and Meta-Analysis.” Clinical Infectious Diseases67 (5): 676–86. https://doi.org/10.1093/cid/ciy182.
47.
United States Conference of Catholic Bishops. 2006. “Ministry to Persons with a Homosexual Inclination: Guidelines for Pastoral Care.” USCCB. November 14.
48.
Van DammeLutCorneliAmyAhmedKhatijaAgotKawangoLombaardJohanKapigaSaidiMalahlehaMookho, et al.2012. “Preexposure Prophylaxis for HIV Infection among African Women.” New England Journal of Medicine367 (5): 411–22. https://doi.org/10.1056/NEJMoa1202614.
49.
Van WifferenFrancineHoornenborgElskeSchim van der LoeffMaarten F.HeijneJannekevan HoekAlbert Jan. 2021. “Cost-Effectiveness of Two Screening Strategies for Chlamydia Trachomatis and Neisseria Gonorrhoeae as Part of the PrEP Programme in the Netherlands: A Modelling Study.” Sexually Transmitted Infections97 (8): 607–12. https://doi.org/10.1136/sextrans-2020-054741.
50.
WinstonCliffordMaheshriVikramManneringFred. 2006. “An Exploration of the Offset Hypothesis Using Disaggregate Data: The Case of Airbags and Antilock Brakes.” Journal of Risk and Uncertainty32 (2): 83–99. https://doi.org/10.1007/s11166-006-8288-7.
