Pre-exposure prophylaxis (PrEP)
Author / Curator: Silya Mazigh, MD
Faculty Advisor: Robin Deutsch, MD
(1) Be concise.
(2) Be evidence-based. (Everything should have a reputable citation and resource)(3) Be clinically relevant. (Avoid unnecessary discussion of pathophysiology and epidemiology if it does not help clinical decision-making).
Top Teaching Points
-Pre-exposure prophylaxis is a way to reduce HIV acquisition using anti-retroviral medications in patients at greatest risk. 
-Tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF-FTC, Truvada) is approved by the FDA. Patients are to take one tablet, once daily.
-Patients must be appropriately evaluated for potential risks and benefits.
Obtain a detailed history to determine the patient's risk for HIV acquisition and the potential benefit from PrEP.
Sexual History - online resources are available to help guide HIV risk stratification (Fenway National Center for LGBT Health, and the CDC website)
- Obtain history of sexual behaviors over the last 6 months.
- Obtain the HIV status and the risk behaviors of the patient's sexual partners.
STI screening - This should be performed even in the absence of symptoms.
- serologic testing for syphilis, and nucleic acid amplification testing or gonorrhea and chlamydia at relevant mucosal sites.
- screening for bacterial vaginosis and trichomonas is not routinely performed; however, it could be considered as their presence suggests recent condomless sex.
Drug using behaviors - obtain history about drug use history over the last 6 months. Factors associated with increased risk include:
- Injecting heroin or cocaine.
- Sharing needles or equipment.
- Using nonparenteral drugs during sex, which may decrease the likelihood of using condoms.
Patients should be evaluated for conditions that could put them at risk for developing ad6erse effects associated with therapy.
Acute HIV - all patients should have plasma HIV testing prior to PrEP.
Preferable with a fourth generation antigen/antibody test.
- A third generation assay is acceptable is an antigen-antibody test is not available and the patient is considered low risk.
- Additional testing for HIV RNA should be performed prior to initiating PrEP in the a subset of patients exhibiting the following:
- signs and symptoms suggestive of acute HIV infection within the previous 4 weeks.
- intermediate antigen-antibody test.
- high-risk exposure within 4 weeks of starting PrEP, regardless of symptoms.
- Do not prescribe TDF-FTC to patients with an estimated GFR rate < 60 mL/min/1.73 m².
- TDF has been associated with acute and chronic kidney disease in HIV-infected patient. The safety has not been studied in HIV-uninfected patients with an eGFR < 60 mL/min/1.73 m².
Active hepatitis B virus infection - patients should be evaluated for the presence of HBV infection prior to initiating PrEP.
- Obtain a hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-Hbc), and hepatitis B surface antibody (anti-HBs).
- Patients should be vaccinated against HBV if they are without evidence of prior infection.
- For those with chronic HBV infection, initiation of PrEP is dependent on the need for treatment of HBV:
- TDF is considered first-line treatment for chronic HBV. For patients who require treatment, this agent can be used as part of PrEP.
- In patient with chronic HBV not requiring treatment, the decision to use TDF-FTC in PrEP is less clear.
- The need for routine bone density screening prior to and after initiation of PrEP is unclear.
- Vitamin D3 plus calcium supplementation was found to mitigate bone loss in HIV-infected patients taking TDF-based therapy.  Although, no data is available on attenuating PrEP-related bone loss. Measures to maintain adequate vitamin D levels could theoretically be helpful.
Pregnancy - women of childbearing age should have a pregnancy test prior to initiating PrEP.
- If pregnant, the risk of acquiring HIV must be weighed again the risk of the use of antivirals. Data on efficacy of PrEP during pregnancy is limited.
- TDF and emtricitabine are both pregnancy category B and are considered safe. However, there are concerns about fetal bone development.
Potential barriers to adherence should be identified and addressed. These include: depression, active substance use, and stigma.
Candidates for PrEP - Ideally, these are patients who are at high risk for HIV, have normal renal function, and are committed to daily medication adherence and close follow-up.
- HIV-uninfected men and women who have an HIV-infected sexual partner with a detectable viral load.
- Men who have sex with men (MSM) and transgender women who have sex with men if, within the last 6 months, they have engaged in high-risk sexual behaviors of had a documented sexually transmitted infection.
- Heterosexually active men who have condomless sex with female partners from regions with generalized HIV epidemics.
- Adolescents - TDF-FTC has only been approved by the FDA for PrEP for patients over 18 years old. Further discussion is warranted if considering PreP in adolescents.
-For HIV-uninfected patients who are at high risk for acquiring HIV and are committed to medication adherence, PrEP using tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) is highly effective.
-TDF-FTC was approved for PreP in 2012.
-For patients who initiate PrEP, TDF-FTC should be taken daily.
-TDF-FTC should be dispensed as a 90-day supply, renewable only after HIV testing.
-The patient should be monitored every 3 months to ensure there are no drug-related toxicities or evidence of HIV acquisition.
-Patients should continue PrEP as long as the risk of infection persists.
-Patients should receive counseling on other risk reduction methods.
Other Teaching Pearls
These should be short one-liners (with citations) of unique or interesting "pearls" that can offer teaching points for more advanced practitioners. (e.g. Losartan is the only ARB hypertensive agent that is associated with a lower incidence of gout attacks )
These are brief one-line summaries of relevant trials and studies. One recommendation is to like to discussion pages like WikiJournalClub for further information.
Ongoing controversies / New updates
What's the latest scuttlebutt? This is a place to include new guidelines, controversies, or other recent updates on the topic.
Core review articles / Guidelines:
- Maartens et al.: HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet 2014;384:258-71.
- Grant et al.: Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 2010;363:2587-99.
- Anderson et al.: Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med 2012;4:151ra125.
- Knox et al.: Multidrug-Resistant HIV-1 Infection despite Preexposure Prophylaxis. N. Engl. J. Med. 2017;376:501-502.
- Hoornenborg et al.: Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report. Lancet HIV 2017;4:e522-e528.
- Sullivan et al.: Estimating the proportion of HIV transmissions from main sex partners among men who have sex with men in five US cities. AIDS 2009;23:1153-62.
- Smith et al.: A Brief Screening Tool to Assess the Risk of Contracting HIV Infection Among Active Injection Drug Users. J Addict Med 2015;9:226-32.
- Marrazzo et al.: HIV prevention in clinical care settings: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA 2014;312:390-409.
- Thigpen et al.: Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N. Engl. J. Med. 2012;367:423-34.
- Baeten et al.: Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 2012;367:399-410.
- Grohskopf et al.: Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States. J. Acquir. Immune Defic. Syndr. 2013;64:79-86.
- Mulligan et al.: Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial. Clin. Infect. Dis. 2015;61:572-80.
- Havens et al.: Association of higher plasma vitamin D binding protein and lower free calcitriol levels with tenofovir disoproxil fumarate use and plasma and intracellular tenofovir pharmacokinetics: cause of a functional vitamin D deficiency?. Antimicrob. Agents Chemother. 2013;57:5619-28.
- Mugo et al.: Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial. JAMA 2014;312:362-71.
- Amico & Stirratt: Adherence to preexposure prophylaxis: current, emerging, and anticipated bases of evidence. Clin. Infect. Dis. 2014;59 Suppl 1:S55-60.
- Grant et al.: Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infect Dis 2014;14:820-9.
- Marrazzo et al.: Tenofovir-based preexposure prophylaxis for HIV infection among African women. N. Engl. J. Med. 2015;372:509-18.
- Abdool Karim et al.: Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010;329:1168-74.
- Mayer et al.: Optimizing Pre-Exposure Antiretroviral Prophylaxis Adherence in Men Who Have Sex with Men: Results of a Pilot Randomized Controlled Trial of "Life-Steps for PrEP". AIDS Behav 2017;21:1350-1360.
- Günthard et al.: Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel. JAMA 2016;316:191-210.
- Frieden et al.: Applying Public Health Principles to the HIV Epidemic--How Are We Doing?. N. Engl. J. Med. 2015;373:2281-7.
- Choi et al.: Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ 2012;344:d8190.