Minor revisions were also made to correct typos, add references, and update content from cited guidelines and source materials.

# Disclaimers:
All material in this publication is in the public domain and may be used and reprinted without permission; citation as to source, however, is appreciated.

# Introduction
Recent findings from several clinical trials have demonstrated safety 1 and a substantial reduction in the rate of HIV acquisition for men who have sex with men (MSM) 2 , men and women in heterosexual discordant couples 3 , and heterosexual men and women recruited as individuals 4 who were prescribed daily oral antiretroviral preexposure prophylaxis (PrEP) with a fixed-dose combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). The demonstrated efficacy of PrEP was in addition to the effects of repeated condom provision, sexual risk-reduction counseling, and the diagnosis and treatment of sexually transmitted infection (STI) that were provided to all trial participants. In July 2012, after reviewing these trial results, the U.S. Food and Drug Administration (FDA) approved an indication for the use of Truvada  (TDF/FTC) "in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk" 5,6 . In July 2013, an additional clinical trial found that daily oral TDF reduced the rate of HIV acquisition for persons who inject drugs (PWID) (also called injection drug users ) 7 .
On the basis of these trial results and the FDA approval, the U.S. Public Health Service has published a comprehensive clinical practice guideline for the use of PrEP for the prevention of HIV infection in the United States and updated it in 2017.  This supplement to the PHS PrEP Clinical Practice Guidelines is intended to provide additional information that may be useful to clinicians providing PrEP. As additional materials become available, this document will be updated.

# Section 1
Contains a template checklist that clinicians can complete and share with patients to document the services provided to PrEP patients and the actions expected from patients to maximize the efficacy and safety of PrEP. Sections 2-4
Contain templates for informational handouts that can be provided to patients Section 5
Contains an information sheet for providers counseling patients about PrEP use during conception, pregnancy and breastfeeding. Section 6
Contains the HIV incidence Risk Index for MSM, a tool that clinicians may use to quickly and systematically determine which men are at especially high risk for acquiring HIV infection, for whom PrEP may be indicated. Section 7
Contains the HIV incidence Risk Index for PWID, a tool that clinicians may use to quickly determine which persons who inject drugs are at especially high risk for acquiring HIV infection, for whom PrEP may be indicated. Section 8
Contains more detailed information about the clinical management of patients who acquire HIV infection while on PrEP. Section 9
Contains more detailed information about the clinical management of transitioning patients from nPEP to PrEP. Sections 10-11 Contain more detailed information than that included in the guidelines about methods and resources for counseling patients receiving PrEP about medication adherence and HIV risk reduction behaviors.

# Sections 12
Contains information relevant to administrative and billing codes for PrEP related services. Section 13 Contains potential practice quality practice measures. Section 14 Documents the methods used to develop the PHS PrEP Clinical Practice Guidelines. Assessment for possible acute HIV infection Indicated laboratory screening to determine indications for these medications An HIV risk assessment to determine whether PrEP is indicated for this patient A medication fact sheet listing dosing instructions and side effects Counseling or a referral for counseling on condom use and any other HIV riskreduction methods this patient may need Advice on methods to help the patient to take medication daily as prescribed Information about PrEP use during conception and pregnancy (when indicated)
A prescription for Truvada (300 mg tenofovir disoproxil fumarate, 200 mg emtricitabine)
A follow-up appointment date
As the provider, I will:
- Limit refill periods to recommended intervals for repeat HIV testing (at least every 3 months)
- Conduct follow-up visits at least every 3 months that include the following:
- Assessment of HIV status (including signs or symptoms of acute HIV infection)
- Assessment of side effects and advice on how to manage them o Assessment of medication adherence and counseling to support adherence o Assessment of STI symptoms, HIV risk behavior and counseling support for riskreduction practices
- Inform the patient of any new information about PrEP and respond to questions
Patient Section
It has been explained to me that:
- Taking a dose of PrEP medication every day may lower my risk of getting HIV infection
- This medicine does not completely eliminate my risk of getting HIV infection, so I need to use condoms during sex
- This medicine may cause side effects so I should contact my provider for advice by calling ________________ if I have any health problems
- It is important for my health to find out quickly if I get HIV infection while I'm taking this medication, so o I will contact my provider right away if I have symptoms of possible HIV infection (fever with sore throat, rash, headache, or swollen glands)
- My provider will test for HIV infection at least once every 3 months Therefore, I will:
- Try my best to take the medication my provider has prescribed every day
- Talk to my provider about any problems I have in taking the medication every day
- Not share the medication with any other person
- Attend all my scheduled appointments
- Call _________________ to reschedule any appointments I cannot attend

# Give one copy to patient
Section 2 PrEP Information Sheet

# Pre-exposure Prophylaxis (PrEP) for HIV Prevention
Frequently Asked Questions What is PrEP? "PrEP" stands for preexposure prophylaxis. The word "prophylaxis" (pronounced pro fil ak sis) means to prevent or control the spread of an infection or disease. The goal of PrEP is to prevent HIV infection from taking hold if you are exposed to the virus. This is done by taking a pill that contains 2 HIV medications every day. These are the same medicines used to stop the virus from growing in people who are already infected.

# Why take PrEP?
The HIV epidemic in the United States is growing. About 50,000 people get infected with HIV each year. More of these infections are happening in some groups of people and some areas of the country than in others.

# Is PrEP a vaccine?
No. PrEP medication does not work the same way as a vaccine. When you take a vaccine, it trains the body's immune system to fight off infection for years. You will need to take a pill every day by mouth for PrEP medications to protect you from infection. PrEP does not work after you stop taking it. The medication that was shown to be safe and to help block HIV infection is called "Truvada" (pronounced tru va duh). Truvada is a combination of 2 drugs (tenofovir and emtricitabine). These medicines work by blocking important pathways that the HIV virus uses to set up an infection. If you take Truvada as PrEP daily, the presence of the medication in your bloodstream can often stop the HIV virus from establishing itself and spreading in your body. If you do not take the Truvada pills every day, there may not be enough medicine in your blood stream to block the virus.

# Should I consider taking PrEP?
PrEP is not for everyone. Doctors prescribe PrEP for some patients who have a very high risk of coming in contact with HIV by not using a condom when they have sex with a person who has HIV infection. You should consider PrEP if you are a man or woman who sometimes has sex without using a condom, especially if you have a sex partner who you know has HIV infection. You should also consider PrEP if you don't know whether your partner has HIV infection but you know that your partner is at risk (for example, your partner inject drugs or is having sex with other people in addition to you) or if you have recently been told by a health care provider that you had a sexually transmitted infection. If your partner has HIV infection, PrEP may be an option to help protect you from getting HIV infection while you try to get pregnant, during pregnancy, or while breastfeeding.

# How well does PrEP work?
PrEP was tested in several large studies with men who have sex with men, men who have sex with women, and women who have sex with men. All people in these studies (1) were tested at the beginning of the trial to be sure that they did not have HIV infection, (2) agreed to take an oral PrEP tablet daily,
(3) received intensive counseling on safer-sex behavior, (4) were tested regularly for sexually transmitted infections, and (5) were given a regular supply of condoms.
Several studies showed that PrEP reduced the risk of getting HIV infection.
- Men who have sex with men who were given PrEP medication to take, were 44% less likely to get HIV infection than were those men who took a pill without any PrEP medicine in it (a placebo). Forty-four percent was an average that included men who didn't take the medicine every day and those who did. Among the men who said they took most of their daily doses, PrEP reduced the risk of HIV infection by 73% or more, up to 92% for some.
- Among men and women in couples in which one partner had HIV infection and the other partner initially did not ("HIV-discordant" couples), those who received PrEP medication were 75% less likely to become infected than those who took a pill without any medicine in it (a placebo). Among those who said they took most of their daily doses, PrEP reduced the risk of HIV infection by up to 90%.
- In one study of men and women who entered the study as individuals (not as a couple), PrEP worked for both men and women in one study: those who received the medication were 62% less likely to get HIV infection; those who said they took most of their daily doses, were 85% less likely to get HIV infection. But in another study, only about 1 in 4 women (<26%) had PrEP medication found in their blood when it was checked. This indicated that few women were actually taking their medication and that study found no protection against HIV infection.
More information on the details of these studies can be found at .

# Is PrEP safe?
The clinical trials also provided safety information on PrEP. Some people in the trials had early side effects such as an upset stomach or loss of appetite but these were mild and usually went away within the first month. Some people also had a mild headache. No serious side effects were observed. You should tell your doctor if these or other symptoms become severe or do not go away.

# How can I start PrEP?
If you think you may be at high risk for HIV, talk to your doctor about PrEP. If you and your doctor agree that PrEP might reduce your risk of getting HIV infection, you will need to come in for a general health physical, blood tests for HIV, and tests for other infections that you can get from sex partners. Your blood will also be tested to see if your kidneys and liver are functioning well. If these tests show that PrEP medicines are likely to be safe for you to take and that you might benefit from PrEP, your doctor may give you a prescription after discussing it with you.
Taking PrEP medicines will require you to follow-up regularly with your doctor. You will receive counseling on sexual behaviors and blood tests for HIV infection and to see if your body is reacting well to Truvada. You should take your medicine every day as prescribed, and your doctor will advise you about ways to help you take it regularly so that it stands the best chance to help you avoid HIV infection. Why is this medication prescribed?
- Truvada is one of several medications that are currently used to treat human immunodeficiency virus (HIV) and hepatitis B virus infection. - Truvada is now being used to prevent HIV infection.
- Truvada is sometimes prescribed to some people who do not have HIV infection (for example, those who do not always use condoms or who have a sex partner that has HIV infection) to help reduce their chances of getting HIV infection - When you take Truvada to prevent HIV infection, doctors refer to this use as "pre-exposure prophylaxis" or "PrEP".

# How does Truvada (PrEP) help prevent HIV infection?
- HIV is a virus that attacks your body's immune cells (the cells that work to fight infections).
- The 2 medications that make up Truvada (tenofovir and emtricitabine) block important pathways that viruses use to set up infection. - If you take Truvada as PrEP daily, the presence of the medication in your bloodstream can sometimes stop the virus from establishing itself and slow the spread of HIV in your body. - By itself, PrEP with Truvada does not work all the time so you should also use condoms during sex for the most protection from HIV infection.
How should this medicine be used?
- You must take one tablet of Truvada by mouth every day.
- Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

# What other information should I know?
- Do not let anyone else take your medication.
- Ask your pharmacist if you have any questions about refilling your prescription.
- Write a list of all of your prescription and over-the-counter medicines, as well as any vitamins, minerals, or other dietary supplements that you take.
- Bring your medication list with you each time you visit a doctor or if you are admitted to a hospital. Keep it with you always in case of emergencies. These signs and symptoms of acute HIV infection can begin a few days after you are exposed to HIV and usually last for about 14 days. They could last for just a few days, or they could last for several months.
You might not realize your illness is acute HIV infection. For one thing, you may not have known that the person you had sex with had HIV infection. And the signs and symptoms of HIV infection may feel just like other common virus infections like flu, a cold, sore throat, or mononucleosis (mono).

# What tests can show that I have acute HIV infection?
When HIV enters your body, it moves inside white blood cells called CD4 lymphocytes. HIV takes over the CD4 cells and makes billions of copies of the virus each day. The virus spread through your body.
Your body tries to defend itself against HIV by making antibodies (these antibodies try to block the virus from spreading in your body And fourth, when people have lots of virus in their body during acute HIV infection, they are more likely to pass the virus on to people they have sex with, especially since they may not know yet that they have gotten infected. For example, if your last HIV test result was negative and your partner also had a recent negative HIV test result, you might choose to have sex without a condom just at the time when it's very likely you would pass the virus on. So the sooner you know you have become infected, the more careful you can be to protect others from getting HIV infection.

# How is HIV treated?
People who have HIV infection are treated with combinations of 3 or more medicines that fight HIV. Some doctors start people on treatment medications as soon as they become infected; other doctors wait for a while because the greatest benefits to a person's health are seen after they have been infected a while. Early treatment also reduces the chances that a person with HIV infection will pass the virus on to their sex partners.

# What do I do if I suspect I might have acute HIV infection?
First, contact your doctor's office and arrange to be examined and have the right blood tests.
Second, discuss with your doctor whether to stop your PrEP medications or continue them until your test results are back.
Third, be especially careful to use condoms and take other safer sex measures to protect your partner(s).

# Section 5 Provider Information Sheet -PrEP during Conception, Pregnancy, and Breastfeeding

# Information for Clinicians Counseling Patients about PrEP Use During Conception, Pregnancy, and Breastfeeding
PrEP use may be one of several options to help protect the HIV-negative male or female partner in a heterosexual HIV-discordant couple during attempts to conceive  . Pregnancy care providers may not have access to the medical records of the partner with HIV infection to document their viral load status. The extent to which PrEP use further decreases risk of HIV acquisition when the partner with HIV infection has a documented current undetectable viral load is unknown.

# Based on DHHS Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission 9
Panel's Recommendations on Reproductive Options for HIV-Concordant and Serodiscordant Couples For Couples who Want to Conceive For Concordant (Both Partners are HIV-Infected) and Discordant Couples:
- Expert consultation is recommended so that approaches can be tailored to couples specific needs (AIII).
- Partners should be screened and treated for genital tract infections before attempting to conceive (AII).
- The HIV-infected partner(s) should attain maximum viral suppression before attempting conception (AIII). For Discordant Couples:
- The HIV-infected partner should be receiving combination antiretroviral therapy and demonstrate sustained suppression of plasma viral load below the limits of detection (AI). - Administration of antiretroviral pre-exposure prophylaxis (PrEP) for 30 days before attempting conception and for 30 days after conception is achieved for HIV-uninfected partners may offer an additional tool to reduce the risk of sexual transmission, particularly if the HIV-infected partner's plasma viral load is unknown or detectable (CIII). It is not known whether PrEP for the uninfected partner confers additional benefit when the infected partner receiving antiretroviral therapy has documented sustained viral suppression.

# Discordant Couples with HIV-Infected Women:
- The safest conception option is assisted insemination, at home or in a clinician's office with a partner's sperm during the peri-ovulatory period (AIII).

# Discordant Couples with HIV-Infected Men:
- The use of donor sperm from an HIV-uninfected man with artificial insemination is the safest option (AIII). - When the use of donor sperm is unacceptable, the use of sperm preparation techniques coupled with either intrauterine insemination or in vitro fertilization should be considered (BII).

# Based on DHHS Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission 9
Panel's Recommendations on Reproductive Options for HIV-Concordant and Serodiscordant Couples
- Semen analysis is recommended for HIV-infected men before conception is attempted to prevent unnecessary exposure to infectious genital fluid. Semen abnormalities appear to be more common among HIV-infected men than HIV-uninfected men (AIII). The following information is provided to help you inform your patients of current information about potential risks and benefits of PrEP use so that you and your patients can make an informed decision.

# Rating of Recommendations

# Key Points
Provide education about PrEP and other methods of conception that minimize the risk of HIV transmission to both members of an HIV-discordant couple whenever possible.

# Options
Reducing the risk of HIV acquisition by an HIV-negative man during conception can be achieved by use of the following, singly or ideally in combination  :
- Antiretroviral treatment of the HIV-positive female partner to achieve an undetectable viral load 13 - STI diagnosis and any indicated treatment for both partners before conception attempts - Daily, oral doses of TDF/FTC beginning 1 month before a conception attempt and continuing for 1 month after a conception attempt. PrEP may be indicated when the partners recent viral load is unknown, reported to be detectable, or cannot be documented as undetectable 14 .

# AND EITHER
- Limit sex without a condom (natural conception) to peak fertility times identified by home or laboratory tests for ovulation 15. OR - Intravaginal insemination 13 (either at home or in the clinic) with a fresh semen sample

# Potential Benefits of PrEP use
In clinical trials with heterosexually active adults, daily oral PrEP with TDF/FTC was safe and reduced the risk of HIV acquisition by an average of 63%-75%. Higher levels of protection (90%) were found among persons whose drug levels in their blood indicated that they had consistently taken the medication 3,4 .

# Potential Risks of PrEP use
In PrEP trials, follow-up with persons taking medication has been conducted for an average of 1-4 years.
Although no serious health risks were associated with PrEP use by HIV-uninfected adults, the long-term safety of PrEP has not yet been determined.

# FOR AN HIV-NEGATIVE WOMAN PLANNING PREGNANCY WITH AN HIV-POSITIVE MALE PARTNER

# Options
Reducing the risk of HIV acquisition by an HIV-negative woman during conception can be achieved by use of the following, singly or ideally in combination 10,13 :
- Antiretroviral treatment of the HIV-positive male partner to achieve an undetectable viral load 13 - STI diagnosis and any indicated treatment for both partners before conception attempts - Daily, oral doses of TDF/FTC beginning 1 month before a conception attempt and continuing for 1 month after a conception attempt. PrEP may be indicated when the partners recent viral load is unknown, reported to be detectable, or cannot be documented as undetectable 14 .

# AND EITHER
- Limit sex without a condom (natural conception) to peak fertility times identified by home or laboratory tests for ovulation in the female partner 15 .

# OR
- Intravaginal 16 or intrauterine insemination, or intracytoplasmic sperm injection with a semen sample processed by "sperm washing" and confirmed to have a negative test result for the presence of remnant HIV  . This option may be indicated for couples with fertility problems.

# Potential Benefits of PrEP use
In clinical trials with heterosexually active adults, daily oral PrEP with TDF/FTC was safe and reduced the risk of HIV acquisition by an average of 63%-75%. Higher levels of protection (90%) were found among persons whose drug levels in their blood indicated that they had consistently taken the medication 3,4 .
The risk of HIV acquisition increases during pregnancy 19 , as does the risk of HIV transmission to an infant born to a mother who becomes infected during pregnancy or breastfeeding 20 Therefore, an HIVnegative woman whose sexual partner/spouse has HIV infection may benefit from continuing PrEP use throughout her pregnancy and breastfeeding to protect herself and her infant a

# Potential Risks of PrEP use
In PrEP trials, follow-up with persons taking medication has been conducted for an average of 1-4 years.
Although no serious health risks were associated with PrEP use by HIV-uninfected adults, the long-term safety of PrEP has not yet been determined.
In PrEP trials women were taken off medication as soon as pregnancy was detected. During these trials, no health problems have been associated with PrEP use by women in early pregnancy or for their offspring. However, the long-term safety of PrEP taken by HIV-uninfected women after fetal (during pregnancy) or infant (during breastfeeding) exposure is not yet determined.
No adverse effects have been found among infants exposed to TDF/FTC when the medications were taken as part of a treatment regimen for HIV-infected women during pregnancy  or during breastfeeding (for which data suggest limited drug exposure  ).
If you prescribe PrEP to a woman while pregnant, you are encouraged to prospectively and anonymously submit information about the pregnancy to the Antiretroviral Use in Pregnancy Registry (/).
a Alth ugh the DHHS Perinatal HIV Guidelines state that "pregnancy and breastfeeding are n t c ntraindicati ns f r PrEP" 9 , the FDA-appr ved package insert 6 says, "If an uninfected individual bec mes pregnant while taking TRUVADA f r a PrEP indicati n, careful c nsiderati n sh uld be given t whether use f TRUVADA sh uld be c ntinued, taking int acc unt the p tential increased risk f HIV-1 infecti n during pregnancy" and "m thers sh uld be instructed n t t breastfeed if they are receiving TRUVADA, whether they are taking TRUVADA f r treatment r t reduce the risk f acquiring HIV-1.". Theref re b th are currently ff-label uses f Truvada.

# Section 6 MSM Risk Index
Epidemiologic studies have identified a wide range or personal, relationship, partner, social, cultural, network, and community factors that may be associated with the presence of HIV infection. However, to provide PrEP (or other intensive HIV prevention services), it is necessary to briefly and systematically screen for key information about those factors that are predictive of very high risk of acquiring HIV infection.
This section contains a tool that clinicians may use to quickly and systematically determine which MSM are at especially high risk of acquiring HIV infection, and for whom PrEP may be indicated.

# Section 7 PWID (IDU) Risk Index
Epidemiologic studies have identified a wide range or personal, relationship, partner, social, cultural, network, and community factors that may be associated with the presence of HIV infection. However, to provide PrEP (or other intensive HIV prevention services), it is necessary to briefly and systematically screen for key information about those factors that are predictive of very high risk of acquiring HIV infection.
This section contains a tool that clinicians can use to quickly and systematically determine which persons who inject drugs (PWID) (also called injection drug users ) are at especially high risk for acquiring HIV infection, and for whom PrEP may be indicated. Add the scores for age and methadone use to the Composite Injection Subscore to yield a Total Score _________ Total Score- - If the total score is 46 or greater, evaluate for PrEP or other intensive HIV prevention services for PWID. If score is 45 or less, provide indicated standard HIV prevention services for PWID. To identify active PWID in a clinician's practice, we recommend asking all their patients a routine question: "Have you ever injected drugs that were not prescribed for you by a physician?" If yes, ask, "When was the last time you injected any drugs?" Only complete PWID risk index if they have injected any nonprescription drug during the past 6 months.

# Section 8 Management of Patients Who Acquire HIV While on PrEP
Patients who are being prescribed PrEP might acquire HIV infection for several reasons. When HIV infection is detected at the first follow-up visit after PrEP initiation, it can indicate that the patient had undetected acute infection when PrEP was initiated. When infection is detected at later follow-up visits, as it most commonly occurs, it might be because patients have stopped taking PrEP, have been taking it infrequently, or have been stopping and restarting it without retesting for HIV infection before restarting. Rarely, despite high adherence to continuous daily dosing, patients taking PrEP have acquired HIV infection. This can occur because of exposure to a drug-resistant viral strain 30 or simply because, even with daily use, PrEP protection is high but not 100% 31 .
In all cases, when an HIV test during a follow-up visit indicates possible infection in a PrEP patient, the following steps should be taken:
- Counsel the patient about their HIV status and the resulting management plan:
- If a single rapid antibody blood test was positive, explain the need to confirm presumptive HIVpositive status with laboratory testing. o If a rapid 4 th generation (antigen/antibody) blood test was positive, explain high likelihood of HIV infection that will need to be confirmed with additional laboratory testing. o If a positive HIV test was based on laboratory testing with confirmatory results already known, explain certainty of HIV diagnosis. o Ask about signs and symptoms of acute infection since last clinic visit as well as PrEP medication adherence history.
- Conduct confirmatory HIV testing (if not completed already) and supplemental tests, if indicated:
- If one or more rapid tests were positive, draw blood for confirmatory laboratory-based HIV testing with adequate blood for reflex HIV viral load testing if confirmed to be HIV infected. o If laboratory-based testing was positive, draw blood for HIV viral load, CD4 cell count, and HIV resistance testing. o For persons with confirmed HIV infection, conduct the following supplemental testing indicated for initiation of HIV treatment, including but not necessarily limited to the following 32 : Chemistry screen, ALT, AST, bilirubin, CBC with differential, urinalysis, and pregnancy test (if female). Fasting lipid profile, glucose, and hemoglobin A1c are also indicated, on the day that seroconversion is detected, if possible.
- Convert the PrEP regimen to an HIV treatment regimen recommended by the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents 32 .
- It is not necessary to stop antiretrovirals entirely while waiting for additional laboratory test results. In the most likely event that the patient has HIV infection, immediate initiation of HIV treatment is indicated. The following regimens are recommended as of July 14, 2016 but the treatment guidelines should be consulted for updates 32 : o Continue the prescription of Truvada (TDF 300 mg/FTC 200 mg) once daily pending results of resistance tests o Add either: Dolutegravir (Tivicay) 50 mg once daily OR Darunavir (Prezista) 800 mg with Ritonavir (Norvir) 100 mg once daily.
In cases where a viral strain with significant resistance to tenofovir is later identified, the regimen can then be optimized. In cases where HIV infection is not confirmed, return to the PrEP regimen can be accomplished by dropping the additional treatment medication.
- Provide client education about time to viral load suppression:
- Reinforce the importance of medication adherence for the patient's long-term health.
- Discuss the importance of condom use to protect sexual partners and provide condoms. o Offer HIV testing for sex and drug injection partners and assistance with disclosure, if desired. o Ask if the patient had condomless sex or shared injection equipment during the past 72 hours, and if yes, offer nPEP for exposed partners.
- Consult with and transfer care to an experienced HIV care provider, if necessary. o Clinicians can call the National Clinical Consultation Center toll-free at (800) 933-3413.
- Discuss or complete insurance paperwork necessary for coverage of treatment medication. o Patients who are receiving medication through PrEP-specific medication assistance programs will need to switch to an HIV treatment assistance program. o Public or private insurance plans will generally not require additional paperwork but prior authorizations for PrEP may raise questions when switching to a prescription for a treatment regimen.
- Schedule follow-up visits (including social services, if required).
- Complete an HIV case report for the health department (completion of fields related to PrEP use at the time of seroconversion are highlighted in red below).

# Section 9 Transition of Patients From Nonoccupational Postexposure Prophylaxis (nPEP) to Preexposure Prophylaxis (PrEP)
Two types of patients may be considered candidates for PrEP use after a course of nonoccupational postexposure prophylaxis (nPEP):
- Patients who request PrEP and also have had a possible sexual or injection drug-related HIV exposure in the prior 72 hours (i.e., are within the recommended window to start nPEP)
- Patients who request repeated courses of nPEP, particularly over a relatively recent period (e.g., more than twice during the past 6 months)
If evaluation demonstrates nPEP is clinically indicated and that the patient is also eligible for PrEP (e.g., behavioral risk for repeated HIV exposure, recent bacterial STI diagnosis in a sexually active person), then these patients should both be provided a 28-day course of nPEP and be evaluated for transition to PrEP at the conclusion of their nPEP course.

# TRANSITIONING IMMEDIATELY FROM NPEP TO PREP
Transitioning from nPEP to PrEP without interruption at the completion of the 28-day nPEP course has the advantages of (1) maintaining satisfactory antiretroviral drug levels for PrEP (if nPEP adherence has been good); and (2) maximizing continuous prevention measures through continuity of nPEP to PrEP care. Essential steps include:
- At conclusion of 28 days of nPEP:
- Repeat a rapid HIV test (ideally with a fourth-generation antigen/antibody assay) and assess for signs and symptoms of acute HIV infection.
- If the rapid HIV test is positive or suspicion exists of possible acute HIV infection, draw blood for confirmatory testing and continue a 3-drug nPEP regimen pending confirmation of HIV status.
- If HIV infection is confirmed, see Section 8 of Clinical Providers' Supplement for indicated next steps.
- If the rapid HIV test is negative and no signs or symptoms of acute infection exist:
Stop the third medication in nPEP regimen and continue TDF/FTC daily as PrEP.
Complete any PrEP baseline laboratory testing not already performed as part of nPEP testing.
Provide medication adherence and risk-reduction support counseling.
Complete any insurance/medication assistance paperwork required to cover PrEP medications (might be different than nPEP medications).
Schedule follow-up visits for HIV, STI, and other laboratory testing as well as medication refills on the basis of standard PrEP clinical practice guidelines recommendations.

# INITIATING PREP AT

# Consultation
Consultation with local or regional experts in nPEP and PrEP, or with the toll-free national PrEPline at 855-448-7737 or PEPline at 888-448-4911, can be sought for clinical scenarios requiring additional information or management options.

# .Section 10 Supplemental Counseling Information -Medication Adherence MEDICATION EDUCATION AND ADHERENCE SUPPORT
Understanding what patients know about PrEP and why they are considering taking it can reveal important information about potential adherence facilitators or barriers. You may wish to begin discussion through a conversation (e.g., "Let's talk. Tell me what you know about PrEP" or "Why do you want to take PrEP?") that can help clarify whether the patient understands the risks and benefits of PrEP given their current sexual behavior and protection strategies, and how their reason(s) for taking PrEP may affect medication adherence.
Adherence to prophylactic regimens is strongly associated with patient understanding of drug information. Patients beginning a PrEP regimen need a very clear understanding of how to take their medications (i.e., when it is to be administered, how many pills to take at each dose) and what to do if they experience problems (e.g., how long outside the dosing window is a dose considered "missed", what to do if they miss a dose). Side effects are often a cause of nonadherence, so a plan for addressing them should be made. It is recommended that you and the patient develop a plan for addressing side effects that the patient would consider intolerable. The plan may include over-the-counter medications that can mitigate symptoms and should stress the need to use condoms consistently if the patient stops taking PrEP medication.
You should also discuss the need for the patient to be tested for HIV every 3 months. Although patients may feel anxious about such frequent testing, it is important that patients understand that frequent testing is needed to prevent drug resistance if they become infected while taking PrEP medication. Be prepared to answer other questions, such as,: "What if people see the medications and think I am HIV-positive?" "Do I need to tell my partner?" "Do I need to take the medication regularly when I am not having sex?"; "Will it help to take extra doses?" "How long can I take the medication?". When you begin a discussion around adherence, emphasize the normalcy of missing occasional doses and the importance of a plan to try to minimize missed doses (see Box 6.1 for an example of how to introduce this issue).

# Box 6.1: Adherence Discussion
You are going to have to take the pill once a day, every day. Although this seems easy, we know that people forget to take their medicines, especially when they are not sick. It will be easier to take your medicine if you think through now some plans about how you'll do it. First, let's briefly discuss your experiences other times you might have taken medicine.
*When you've taken medicines before, how did you remember to take them?
Please tell me about any problems you had taking your pill.
*What was most helpful for remembering to take them?
An adherence plan should include the following: (1) tailoring the dosing time to correspond with the patient's regularly scheduled activities so that medication taking becomes integrated into the patient's daily routine, (2) using reminders or technical devices (e.g., beepers, alarms) to minimize forgetfulness, (3) considering organizational needs and tools (e.g., calendars, strategies for weekends away from home) to address changes in routine and schedule, and (4) reviewing disclosure issues to identify those who can support the patient's intentions to adhere or barriers to adherence due to lack of disclosure/privacy at home. (See Box 6.2 for sample questions.)

# Box 6.2: Developing an adherence plan
OK, now let's come up with a plan for taking your medicine.

# Scheduling
What is your schedule like during a typical week day? At what point in the day do you think it would be easiest to take the pill? That is, is there a time when you are almost always at home, and not in too much of a rush? How does your schedule differ on weekends?

# Reminder devices
How will you remember to take the pill each day? One way to remember is to take the pill at the same time that you are doing another daily task, such as brushing your teeth or eating breakfast. Which of your daily tasks might be used for this purpose? Try to pick something that happens every day. Sometimes we might pick something that is not always done on the weekends or during other days, and then we are more likely to forget. (For example, ... One potential example follows: sometimes I don't shave on Saturdays, but I always brush my teeth, so linking taking the medicine to brushing my teeth might be better than linking it to shaving.) It also helps to store the pills near the place where you perform this daily task. Some people use a reminder device to help them remember. Do you have any reminder devices that you have used in the past? For example, watches, beepers, or cell phones.

# Organizational skills
Where will you store the bottle of pills? When you travel or spend the night outside of your home, what will you do about taking the pill?

# Social support & disclosure
Who in your household will know the reason that you are taking the pills? Are they supportive of you taking them? Are there individuals who might make assumptions about your serostatus because you have these medicines?
You may wish to explore other potential barriers that emerged in initial conversations (e.g., beliefs and attitudes), including factors (e.g., as substance use, depression or unstable housing) known to negatively affect medication adherence, such. To adhere to PrEP medication well, some patients may need access to mental health or social services.

# MONITORING PREP PATIENTS: ASSESSING SIDE EFFECTS AND ADHERENCE
Assess medication adherence as well as adherence to HIV testing at every visit. Self-reported adherence is typically an overestimate of true adherence, but patients may over report their adherence when they fear that a more accurate report would results in a negative judgment from their clinician. When asking patients about their adherence, do your best to adopt a nonjudgmental attitude, giving the patient permission to share adherence difficulties without worrying that you will reproach them. Asking patients to help you understand how they are doing with their medications will provide more information and thus allow for a better diagnostic picture of a patient's needs than will a more prescriptive approach.
Begin follow-up visits by asking the patient how well they have been doing with taking all of their medicines as scheduled. Accept more general responses (e.g., "so so", "pretty good", "excellent", "perfect") before asking for specific information about the frequency and the context of missed doses. Provide reinforcement for patients who report that they are doing well: ask questions such as "What are you doing to keep this going so well?" or "That's great. Can you see anything getting in the way of this?" These exchanges can help solidify the factors that are supporting your patients' adherence while helping them prepare for any barriers that may arise in the future.
When talking with patients who are not reporting perfect adherence, ask as to how many doses they have missed during a specific period. Assessing a longer period (e.g., 30 days, 7 days) is preferred to shorter periods (e.g., 3 days), not only because adherence can vary with changes in schedule (e.g., weekends, holidays) that may not have occurred during the shorter assessment period, but because many patients increase medication-taking just before medical appointments, a phenomenon supported by blood level assessments in the iPrEx trial. 2 When asking about many doses were missed (e.g., "In the last 30 days, how many times have you missed your PrEP medication?"), also (1) ask whether this was typical since their last clinic visit in order to gain a sense of adherence patterns, (2) ask for specific information about when they most recently missed dose(s), and (4) determine the circumstances during which those missed doses occurred (e.g., "Where were you?" "Who were you with?" "What happened just before you were supposed to take your medicine?"). Asking what happened on the day the dose was missed, and getting the patient's perspective on what generally gets in the way of taking medications regularly, will facilitate a conversation that will help to identify the patient's specific adherence barriers as well as the type of adherence support the patient needs.
On the basis of this conversation, develop a plan to address adherence barriers. Questions such as "What do you think you can do differently?" "What things make it easier to take your medications?" "What things need to happen for you to take your medications regularly?" or "What might you try ?" bring the patient into the planning process and thus facilitate identification of the strategies most likely to be implemented. It's important for you to be familiar with a range of adherence strategies that can be shared with patients who require help with this task.
Finally, assess whether the patient is experiencing any side effects of medication, the severity of the side effects, and their role as an adherence barrier determined. Currently, most of what is known about antiretroviral therapy (ART) side effects is derived from patients with HIV. Healthy people may be more concerned about side effects than HIV patients. Try to determine whether clinical symptoms attributed to PrEP medication could possibly be due to other disorders (e.g., depression) or natural processes (e.g., aging). If necessary, include medications to treat side effects in the adherence plan.

# Section 11 Supplemental Counseling Information -HIV Risk Reduction
Determining whether the patient is a good candidate for PrEP is not strictly objective, and should be based on an ongoing discussion between you and your patient. Risk screening can be conducted using various approaches: face-to-face interviews, written forms, or computer-based tools. Written forms and computer-based tools are effective and can be conducted with fewer staff resources 33 . However, self-administered written forms are not recommended for persons with low literacy.
Using risk screening information and the HIV test results, provide your patients with services that are appropriate for their level of risk and are tailored to their prevention needs. Patients who report no or few risk factors, may have minimal prevention needs. In the absence of other information, these patients do not need PrEP. For patients for whom PrEP is appropriate, provide risk-reduction counseling and support services before, during, and after PrEP you prescribe PrEP.

# SEXUAL RISK REDUCTION COUNSELING
Address the sexual health of your patients, including risk behaviors that increase the likelihood of acquiring HIV or other sexually transmitted infections. Several discussion areas are recommended even in brief discussions of sexual risk behavior. For patients who demonstrate an elevated risk of sexual HIV acquisition, provide a brief risk reduction intervention onsite or link them to a program that provides those services (see ). For patients who are continuing to engage in high-risk sexual behaviors or who need additional prevention services (beyond a brief risk-reduction intervention), link them to a program that provides more intense interventions, such as those in the Compendium of Evidence-based HIV Prevention Interventions (see ) which are often provided by local health departments or community-based organizations. These patients may also be good candidates for continued use of PrEP until they are consistently practicing effective behavioral risk reduction.
Counseling patients who test HIV-negative. Guidelines have emphasized the importance of risk-reduction counseling for persons determined to be at substantial risk of sexual HIV acquisition 34 . It is recommended that you select the most appropriate brief sexual risk-reduction intervention that can address the immediate prevention needs of HIVnegative patients at substantial risk for acquiring HIV infection. One counseling approach designed for STD clinic providers, the RESPECT model 35 , can be used. The model consists of two brief, 20-minute, interactive, patient-focused counseling sessions that are conducted during HIV testing, and have been found to significantly reduce sexual risk behaviors and prevent new STDs among HIV-negative patients (although not HIV incidence). Besides RESPECT, there are now several other effective brief sexual riskreduction intervention models that should be considered when providing HIV-negative patients appropriate prevention counseling. Although no brief counseling models have yet proven effective for patients taking PrEP, some of the models developed for persons with HIV infection, (Partnership for Health 36 , and motivational interviewing 37,38) may be appropriate for adaptation to counseling patients who are taking PrEP.
Intensive sexual risk reduction interventions may be appropriate for some patients, who should be referred to appropriate providers. In general, HIV risk-reduction interventions have been shown through numerous systematic reviews, to be efficacious in reducing HIV sexual risk behaviors, promoting protective behaviors, and reducing the incidence of new sexually transmitted infections among high-risk populations from various demographic, racial/ethnic, or behavioral risk groups 39,40 .
Counseling patients who test HIV-positive. Provide emotional support and counseling to patients who receive preliminary or confirmed positive HIV test results to help them understand the test result, the benefits of initiating and remaining in HIV medical care, and the importance of reducing their HIV-related sexual and/or injection risk behaviors to help protect their health and the health of their partners. Link all HIV-positive patients to HIV medical care, prevention services that routinely offer risk screening and ongoing risk-reduction interventions, and other health services as needed.

# PREP FOLLOW-UP VISITS
Provide brief behavioral HIV risk assessment and supportive counseling at each follow-up visit while the patient is taking PrEP medication. For important components of these sessions, see Box 7.1. At least annually discuss with the patient whether discontinuation of PrEP is warranted.
If the decision is made to discontinue PrEP, a plan for periodic reassessment should be made and any indicated referrals to community programs or other support services should be arranged.

# Box 7.1: Elements of brief HIV risk-reduction counseling in clinical settings
Create and maintain a trusting and confidential environment for discussion of sexual or substance abuse behaviors.
Build an ongoing dialogue with the patient regarding their risk behavior (and document presence or absence of risk behaviors in the confidential medical record).
Reinforce the fact that PrEP is not always effective in preventing HIV infection particularly if used inconsistently, but that consistent use of PrEP together with other prevention methods (consistent condom use, discontinuing drug injection or never sharing injection equipment) confers very high levels of protection. Encounter for preprocedural laboratory examination (blood and urine tests prior to treatment or procedure) Z11. 3 Encounter for screening for infections with a predominantly sexual mode of transmission Z11. 4 Encounter for screening for human immunodeficiency virus (HIV) Z11.59
Encounter for screening for other viral diseases Z11. 8 Encounter for screening for other infectious and parasitic diseases Z13.89
Encounter for screening for other disorder (encounter for screening for genitourinary disorders) Z13.9
Encounter for screening unspecified

# Section 14 Methods for Developing the PrEP Clinical Practice Guideline
In 2009, in recognition of the lead time needed to develop clinical guidance for the safe and effective use of PrEP should clinical trials results support it, CDC initiated a formal guidelines development process to allow for early review of the relevant literature, discussion of potential guidelines content given scenarios of potential trial results, and fostering the development of expert and stakeholder consensus. This process was designed to provide a basis for the rapid issuance of interim guidance, to be followed by Public Health Service guidelines as soon as the earliest trial findings indicated sufficient PrEP efficacy and safety to merit its implementation for HIV prevention through one or more routes of transmission.
This guidelines development process was based on a review of experience with the development of other clinical and nonclinical guidelines at CDC, including those for STD treatment and antiretroviral prevention of mother-to-child transmission following the ACTG 076 trial results.
There were five basic components to the process for developing the 2014 PrEP guidelines:
1. An HHS Public Health Service (PHS) Working Group to develop interagency consensus on major points of implementation policy and provide agency review of guidelines. This working group included representatives from agencies that would formally clear PHS guidelines (FDA, HRSA, NIH, HHS/OHAP) as well as agencies that may implement such guidance (IHS, VA). The working groups and expert panels listed here were convened by teleconference before trial results were available (2009-2010) and some were reconvened after each trial results for each population group were published. As technical experts, prevention partners, and key stakeholders, they were asked to assist us to identify relevant scientific/medical literature and share thoughts on topics that would inform the Data from the clinical trial, human observational study, and laboratory human study results were added to the evidence tables. Study findings presented in the evidence tables were each assessed for quality of the study using GRADE criteria 39 (see guidelines Appendix 1, Table 13). Then all data supporting a specific recommendation were given a summary strength of evidence rating (across all studies relevant to that recommendation) using the same system as used for the DHHS antiretroviral treatment guidelines 32 (see PrEP clinical practice guidelines Appendix 1, Table 12).

# DRAFT GUIDELINE WRITING AND REVIEW PRIOR TO PUBLICATION
The draft was written to address guidelines standards for review of the strength of evidence (GRADE approach 41 ) as well as a format designed to promote guideline implementation (GLIA 42 ), dissemination (GEM 43 ), and adoption (AGREE 44,45 ).
The 2014 draft clinical practice guideline and clinical providers supplement were reviewed by CDC, FDA, NIH, HRSA, and HHS, and a series of webinars were held in 2012 and 2013 to obtain additional expert opinion and public engagement on draft recommendations for PrEP use.
The draft guideline and supplement were then reviewed by a panel of 6 external peer reviewers who had not been involved in their development. At each step, revisions were made in response to reviewer and public comments received.
For the 2017 update, the 2014 systematic review of published literature was updated through June 2017. Although no changes to the graded recommendations were indicated, additions to the evidence review tables were made; minor clarifying edits to the supporting text were made to enhance consistency with recently updated STD, nPEP, and perinatal guidelines sections relevant to PrEP; and updated references were added. These changes were shared with a group of 4 external peer reviewers for comment.

# Plans for Updates to the Guideline
PrEP is a rapidly changing field of HIV prevention with several additional clinical trials and studies are now underway or planned. Updates to these guidelines are anticipated as studies provide new information on PrEP efficacy, HIV testing, drug levels, adherence, longer term clinical safety, and changes in HIV risk behaviors associated with PrEP medication use for HIV uninfected MSM, heterosexuals, injection drug users, pregnant women and their newborns; as well as information on the efficacy and safety of other antiretroviral medications, and other routes and schedules of medication delivery for PrEP.
When significant new data become available that may affect patient safety or graded recommendations for PrEP use, an announcement with suggested revisions to the existing guidelines will be posted on the CDC web site and the public will be given a 2-week period to submit comments. These comments will be reviewed and a determination made as to whether additional revisions are indicated. Final updated guidelines will then be posted on the CDC web site.
This process allowed wide input, transparency in discussing the many issues involved, time for the evolution of awareness of PrEP and ideas for its possible implementation, in addition to facilitating the development of a consensus base for the eventual guidance. At the same time, it allowed for guidelines based on expert opinion, and recommendations deemed feasible by clinical providers and policymakers.
On the basis of results from the first 4 activities listed above and the publication in late November 2010 of results from the first clinical trial to show substantial efficacy and safety 2 , CDC issued interim guidance for PrEP use among men who have sex with men in January 2011. This interim guidance was followed by a face-to-face meeting of external in May 2011. As efficacy and safety results were published, additional interim guidance documents were issued for heterosexually active adults (August 2012) and injection drug users (July 2013).

# SYSTEMATIC LITERATURE REVIEW METHODS
For the 2014 guidelines, a systematic review was conducted of PrEP studies published from January 2010 through December 2013. For the 2017 guidelines, the same search strategy was run to update studies published through June 2017. Searches were conducted of MEDLINE, Embase, CINAHL, and Cochrane Library databases. The search strategy used the following criteria:
- Pre-Exposure Prophylaxis/ OR Chemoprevention/ OR (((Preexposure OR Pre-exposure) adjacent to prophylaxis) OR PrEP OR (topical adjacent to (prevention OR prophylaxis OR microbicide- OR gel OR pericoital OR precoital OR vaginal OR rectal OR anal)) OR chemoprophylaxis OR chemoprevention OR chemo-prophylaxis OR chemo-prevention OR iPrEX).mp. - AND - (exploded terms) Anti-HIV Agents/ OR Anti-Retroviral Agents/ OR HIV Infections/pc OR ((HIV OR human immunodeficiency virus) AND (antiretroviral- OR anti-retroviral- OR antiretrovirus- OR anti-retrovirus- OR Truvada OR tenofovir OR emtricitabine OR (TDF ADJ5 FTC))) - AND NOT animals - in the title, abstract, keyword heading word, subject heading fields Retrieved citations were provided in an Endnote reference file for deduplication. Then 2 scientists independently reviewed the citations and removed those that were not published in English, did not contain data (e.g., editorials, reviews, news reports), or did not contain data about oral TDF/FTC for PrEP. The next step was to screen citations to remove those that did not contain new data about oral PrEP (data/analyses not previously published). For the 2017 update, year of publication, author, and titles were compared with the 2014 Endnote library as necessary to identify already exiting entries. During this step, abstracts or full articles were read and publications were categorized into the following groups.
- New clinical trial results
- New human observational study results - New survey, focus group, or other behavioral study results
- New cost analysis results (e.g., program cost, cost benefit analysis)
- New modeling results (e.g., impact models)
- New laboratory human study results (e.g., drug levels, resistance)
- None of the above
The coding by the two reviewers was then compared and discrepancies were reconciled.
Citations with no new data about daily oral PrEP with TDF/FTC were deleted from the updated Endnote 2017 library.