Posted January 2014
- In May 2014, the Centers for Disease Control and Prevention (CDC) released its guidelines for the use of daily pre-exposure prophylaxis (PrEP) for the prevention of HIV infection. The following CDC PrEP documents are available:
New York State Summary on Pre-Exposure Prophylaxis to Prevent HIV Infection
The New York State Department of Health AIDS Institute (NYSDOH AI) supports the addition of pre-exposure prophylaxis (PrEP) to the menu of evidence-based interventions to prevent HIV transmission. Throughout its history, the NYSDOH AI has been a leader in recommending biomedical interventions to prevent HIV infection, beginning with establishing a standard of care for the prevention of mother-to-child HIV transmission, using antiretroviral agents during pregnancy and labor and delivery, and as prophylaxis for the newborn. Since 1991, NYSDOH AI has recommended a combination of antiretroviral agents for post-exposure prophylaxis to prevent HIV transmission in the context of occupational and non-occupational exposures. NYSDOH AI has recently recommended that all patients living with HIV be evaluated for initiation of antiretroviral therapy (ART). This recommendation is based on increasing evidence that patients with established HIV infection benefit from ART at all stages of disease and on recent data that demonstrate a dramatic reduction of HIV transmission risk from ART-treated patients, which is a strategy commonly known as “treatment as prevention.”
Over the past few years, studies evaluating the efficacy of PrEP have shown promising results. On the national level, the Centers for Disease Control and Prevention has issued interim guidance for men who have sex with men (MSM), heterosexually active adults, and injection drug users in January 2011, August 2012, and June 2013, respectively. In July 2012, the Food and Drug Administration approved the use of tenofovir + emtricitabine (TDF/FTC, Truvada) for use of PrEP in adults.
Although the overall number of new HIV infections is decreasing in New York State, some subpopulations, such as young men who have sex with men (YMSM), continue to show a rise in the rate of newly acquired HIV infection. In addition, new infections continue to be disproportionately higher in communities of color. PrEP may be an effective option to augment behavior change in these high-risk populations.
The NYSDOH AI recognizes that a comprehensive system-wide approach is necessary to ensure that patients are effectively managed on PrEP, and that individuals throughout the State who will most likely benefit have access to PrEP. Key populations that are most at risk for HIV, such as MSM, serodiscordant couples, and injection drug users, should be prioritized for outreach and access to ensure that they are aware of PrEP and its benefits. In New York State, there is a broad network of community-based providers, including local health departments and STD clinics, that offer a full range of prevention, primary care, and supportive services to high-risk individuals. This network provides a firm foundation upon which to base targeted efforts to identify high risk-individuals and replicate, to the extent possible, the approaches used in the highly successful clinical trials of PrEP.
To better understand the use of TDF/FTC as PrEP, New York State will promote effective use of this biomedical intervention through this clinical guidance document, provider implementation protocols, and ongoing educational programs.
Following is a summary of the key principles that are described in this document.
In September 2012, the New York State Department of Health convened a PrEP Advisory Panel to develop clinical guidance on the use of PrEP. The Panel consisted of primary care providers caring for high-risk populations, clinicians experienced in the treatment of HIV, obstetricians, adolescent care providers, pharmacists, program administrators, social workers, policy makers, representatives from the New York City Department of Health and Mental Hygiene, and consumer representatives.*
The following document provides guidance for delivery of an HIV prevention program that includes the use of PrEP. This guidance is based on the results of the clinical trials of PrEP, a review of published data, and the interim guidance documents from the Centers for Disease Control and Prevention (see Section IX: Resources). Available data are limited regarding the best practices for monitoring the use of TDF/FTC in non-HIV-infected individuals in the clinical setting. When there were no data on which to base recommendations, recommendations were formulated based on both expert opinion and experience with use of these agents in the HIV-infected population.
This PrEP guidance document is intended for practitioners in all clinical practice settings where PrEP will be prescribed and monitored, including primary care, HIV care, STI clinics, emergency departments, and community-based centers. The information has been formatted as a series of tables and checklists to be easily used at the point of care in a variety of settings. This guidance document will be updated annually as new data are published and more experience is accumulated with the use of PrEP.
* Prior to participation, each panel member submitted a financial disclosure form in accordance with the program’s conflict of interest policy. Two panel members reported potential conflicts with Gilead, manufacturer of Truvada. JB-M, Speaker’s Bureau; AU, Speaker’s Bureau.
HIV prevention through pre-exposure prophylaxis (PrEP) involves the use of antiretroviral medications by non-HIV-infected individuals to reduce their risk of acquiring HIV. In July 2012, the Food and Drug Administration (FDA) approved the use of tenofovir + emtricitabine (TDF/FTC) for HIV PrEP in adults who are at high risk for becoming HIV-infected.
Use of tenofovir alone and tenofovir + emtricitabine as PrEP has been studied in clinical trials in several populations, including men who have sex with men,1 heterosexual discordant couples,2 heterosexual men and women,3-5 transgender women,1 and injecting drug users.6 All of the trials found PrEP to be safe. Four trials found PrEP to be effective for preventing HIV infection when taken as prescribed. The FEM-PrEP4 and VOICE trials5 did not show a benefit, likely because of poor adherence to the daily PrEP regimen. See Appendix A for a summary of results from the clinical trials.
PrEP has not been studied in individuals younger than 18 years of age. Studies of other antiretroviral agents for use as PrEP, such as maraviroc, rilpivirine, and dapivirine, are underway.
PrEP should not be offered as a sole intervention for HIV prevention. PrEP should only be prescribed as part of a comprehensive prevention plan that includes counseling and education about the following:
- Consistent and correct condom use
- Safer-sex practices and risk-reduction counseling
- Adherence to PrEP
- Importance of frequent HIV testing and screening for other sexually transmitted infections (STIs) that can facilitate HIV transmission
- For individuals in serodiscordant relationships, the importance of suppressive ART (treatment as prevention) for HIV-infected partners
III. CANDIDATES FOR PRE-EXPOSURE PROPHYLAXIS
PrEP is indicated for individuals who have a documented negative HIV test result and are at ongoing high risk for HIV infection. A negative HIV test result needs to be confirmed as close to initiation of PrEP as possible, ideally on the same day the prescription is given (see Section V: Pre-Prescription Assessments, Education, and Laboratory Tests). PrEP should only be prescribed to those who are able to adhere to the regimen and express a willingness to do so.
PrEP is not meant to be used as a lifelong intervention, but rather as a method of increasing prevention during periods when people are at greatest risk of acquiring HIV. The length of use will depend on the individual’s behaviors, which may change over time. Providers need to obtain a thorough sexual and drug use history and regularly discuss risk-taking behaviors with their patients to assess candidacy for PrEP, encourage safer-sex practices and safer injection techniques (if applicable), and assist in the decision of when to use PrEP and when to discontinue use.
Other individuals may qualify for PrEP who may not fit within the above risk categories. Decisions to initiate PrEP should be individualized by weighing patients’ personal risk of acquiring HIV infection against the potential benefits and risks of TDF/FTC.
Individuals who do not necessarily have continued risk for acquiring HIV but may have episodic exposures may be good candidates for non-occupational post-exposure prophylaxis (nPEP) rather than PrEP. For example, nPEP may be a better option for an individual who uses condoms regularly, but may experience an occasional broken condom or lapse in use. These individuals should be educated about nPEP and the need to receive medication within 36 hours of the exposure.
A 7-item screening index has been developed to identify MSM who are at risk of HIV seroconversion (see Appendix B).
Use of PrEP to Prevent HIV Transmission During Attempts to Conceive
PrEP may be one option to help protect the HIV seronegative partner in a serodiscordant relationship during attempts to conceive. Risk of HIV transmission may be further reduced in serodiscordant sexual relationships when the HIV-infected partner is receiving suppressive ART. Data supporting treatment as prevention are strongest for heterosexual couples based on the findings of HPTN 052.14 These data have been extrapolated to MSM although primary data supporting “treatment as prevention” in this population are lacking.
IV. PrEP: CONTRAINDICATIONS AND CONSIDERATIONS
Although consistent condom use is a critical part of a prevention plan for all people prescribed PrEP, lack of use of barrier protection is not a contraindication to PrEP.
The considerations outlined in Table 3 are not absolute contraindications to prescribing PrEP. Clinicians should consider these factors and proceed with caution.
V. PRE-PRESCRIPTION ASSESSMENTS, EDUCATION, AND LABORATORY TESTS
Following is a series of tables, formatted as checklists, that outline what this Panel believes are the essential assessments, patient education, and laboratory tests that need to be performed before a prescription for PrEP is given.
Once it is decided that the patient is a candidate for PrEP according to the criteria in Table 1, further assessments (listed in Table 4) are needed to clearly understand the prevention needs of the individual patient and whether initiation of PrEP is an appropriate option. Patient education is critical to shared decision-making and the success of PrEP as part of the prevention plan. Tables 4 and 5 provide the basis from which shared decision-making about initiation of PrEP can occur, providing the clinician with the opportunity to educate the patient about risks, benefits, and options, while providing the patient with the opportunity to discuss preferences, needs, and individual circumstances. Medication adherence may be improved when patients participate in treatment decisions.15
Patients need to understand how PrEP works, including risks and benefits, the need for strict adherence to maintain protective drug levels, and what it will and will not do for them. Explanations should be given in the patient’s native language and should be easy to understand. For example: The pill Truvada has two drugs in it that are commonly used to treat HIV in persons who are HIV-positive. When taken daily by people who are HIV-negative, they can block HIV from infecting the body. The pill needs to be taken every day in order for the body to build up sufficient drug levels to block HIV. It cannot be expected to work if it is only taken just before or just after sex. PrEP reduces but does not eliminate HIV transmission risk. You still need to use condoms even if you are taking PrEP because PrEP does not protect against other sexually transmitted diseases.
Table 5 lists the areas to educate patients about before prescribing PrEP.
Pre-Prescription: Laboratory Tests
The laboratory tests listed in Table 6 should be obtained at the pre-prescription visit. It is imperative that a negative HIV test result is confirmed as close to initiation of PrEP as possible, ideally on the same day the prescription is given. Clinicians should wait to prescribe PrEP until confirmation of a negative test result is available. Drug-resistant HIV has been found in patients with undiagnosed HIV who were using TDF/FTC as PrEP. If the HIV test result is not immediately available, it may be necessary to inform the patient of a negative test result by phone with the option for the clinician to either call in the prescription or schedule another visit.
When patients are engaged in care to receive PrEP, providers should use the opportunity to administer vaccinations for HAV, HBV, HPV, and meningococcus as indicated.*
* See the Centers for Disease Control and Prevention’s adult schedule for immunizations for non-HIV-infected adults. See New York State Department of Health recommendations for vaccinating against meningococcal disease.
VI. PRESCRIBING PrEP
Table 7 provides the recommended regimen for TDF/FTC when used for a PrEP indication. The first prescription should only be for 30 days to allow for a follow-up visit to assess adherence, tolerance, and commitment. At the 30-day visit, a prescription for 60 days may be given; the patient should then return for 3-month HIV testing and other assessments (see Table 8). After that visit, prescriptions can be given for 90 days, provided that the patient is adherent.
Figure 1 provides a general guide for the schedule of visits and follow-up assessments in the first year of receiving PrEP.
VII. PrEP FOLLOW-UP MANAGEMENT AND MONITORING
Patients receiving PrEP require regular visits, at least every 3 months, to monitor HIV status, adherence, and side effects. Follow-up and monitoring of patients receiving PrEP also includes prevention services that are part of a comprehensive prevention plan, such as risk-reduction counseling, access to condoms, STI screening, and mental health and substance use screening, when indicated.
Table 8 lists the elements of a follow-up visit for patients receiving PrEP.
Adherence and Retention in Care
In all studies of PrEP, efficacy is highly dependent on adherence. For patients who report intermittent use, more frequent visits may be necessary to reinforce adherence. Some providers use patient contracts to reinforce adherence to medication and appointments. Some providers may contact the pharmacy to confirm that medication is being refilled at time intervals consistent with adherence (e.g., every 30 days if 30-day supply given). If patients are consistently unable to adhere to the regimen, PrEP should be discontinued, and tailored risk-reduction messages should be delivered.
For patients who are not receiving routine primary care, PrEP is an opportunity for engagement and retention in care. Engagement in primary care should be strongly encouraged, and health maintenance, such as immunizations and standard age-appropriate prevention screening should be offered. Clinicians should partner with providers within or outside of their organization to provide services, including subspecialty services, mental health and substance use treatment, case management, navigation and linkage services, housing assistance, and income/benefits assessments. Referrals should also be made to support groups if indicated. See the HIV Patient Resources Directory for services listed by region.
Discussions about risk reduction should be tailored according to the patient’s individual needs (see Appendix C for a detailed listing of AIDS-Institute-funded HIV prevention programs that provide risk-reduction counseling). Clinicians should provide condoms at every visit, and should discuss use of effective contraception and desire to use contraception. PrEP users should be counseled to continue use of condoms while using PrEP (see Prevention with Positives, Appendix B, for more information about types of condoms and proper use).
For patients in serodiscordant relationships with HIV-infected partners who are not receiving ART, clinicians should recommend treatment for the HIV-infected partner and should reinforce this message at each visit.
For injection drug users, clinicians should make referrals for substance use treatment and should prescribe clean syringes and needles and refer to needle-exchange programs. New York State’s two syringe access initiatives are the Expanded Syringe Access Demonstration Program and Syringe Exchange Programs.
Routine HIV testing is an integral component of safe use of PrEP. Frequent screening is meant to prevent the development of resistance in PrEP users who become HIV-infected while using PrEP, as well as protect transmission to HIV-negative partners. Quarterly testing with an HIV antibody test that is third-generation or higher is recommended (see list of available 3rd and 4th generation HIV tests).
HIV testing should also occur whenever patients present with symptoms of acute HIV infection. If acute HIV infection is suspected, an HIV serologic screening test should be used in conjunction with a plasma HIV RNA assay; a fourth-generation HIV antigen/antibody combination test is the preferred serologic screening test if available. Detection of HIV RNA or antigen in the absence of HIV antibody should be considered a preliminary positive result. More detailed recommendations for testing for acute HIV infection are available (see Diagnosis and Management of Acute HIV Infection).
Discontinue PrEP immediately for patients who receive a positive HIV test result. Obtain a genotypic assay, and refer and link to HIV care.
The most common side effects of TDF/FTC are headache, abdominal pain, and weight loss; however, these side effects usually resolve or improve after the first month. Two weeks after initiation of PrEP, clinicians should follow up either in person or by phone to assess side effects. Standard measures, such as antidiarrheal agents, anti-gas medications, and antiemetics, should be used to alleviate gastrointestinal side effects as needed.
Use of TDF/FTC in HIV-infected patients has shown that side effects, such as renal impairment or bone density loss, can occur. Although uncommon, regular laboratory monitoring for these parameters is necessary (see Table 8). If a decrease in serum creatinine and calculated creatinine clearance is observed, potential causes should be evaluated.
Pregnancy Screening and Management
Pregnancy tests should be obtained at each follow-up visit for women. Clinicians should discuss the known risks and benefits of taking TDF/FTC during pregnancy. Continuation of PrEP during pregnancy is an individualized decision based on patient preference and whether there are ongoing risks for HIV during pregnancy. The patient’s obstetrical provider should be informed of the use of TDF/FTC during pregnancy.
VIII. DISCONTINUATION OF PrEP REGIMEN
PrEP should be discontinued immediately upon receipt of a positive HIV test result; genotypic resistance testing should be performed, and patients should be referred and linked to HIV care. Clinicians need to be vigilant for signs of potential HIV seroconversion in patients receiving PrEP (see Table 5 for a list of signs and symptoms of acute seroconversion). If symptoms of acute seroconversion develop, PrEP should be discontinued until HIV-negative status is confirmed by HIV RNA testing; recommendations for testing for acute HIV infection should be followed (see Diagnosis and Management of Acute HIV Infection for guidance on screening for acute infection).
Other indications for discontinuation of PrEP are listed in Table 9. When discontinuing PrEP in patients who have chronic hepatitis B virus, close monitoring for rebound viremia is recommended.
Interim Guidance from the Centers for Disease Control and Prevention:
- Centers for Disease Control and Prevention. Interim guidance: Preexposure prophylaxis (PrEP) for the prevention of HIV infection in men who have sex with men. Morb Mortal Wkly Rep 2011;60:65-68. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm6003a1.htm
- Centers for Disease Control and Prevention. Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. Morb Mortal Wkly Rep 2012;61:586-589. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a2.htm
- Centers for Disease Control and Prevention. Update to interim guidance for pre-exposure prophylaxis (PrEP) for the prevention of HIV infection: PrEP for injecting drug users. Morb Mortal Wkly Rep 2013;62:463-465. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm6223a2.htm
World Health Organization. Guidance on oral pre-exposure prophylaxis (PrEP) for serodiscordant couples, men and transgender women who have sex with men at high risk of HIV: Recommendations for use in the context of demonstration projects; July 2012. Available at: www.who.int/hiv/pub/guidance_prep/en/index.html
Truvada Risk Evaluation and Mitigation Strategy (REMS) Materials:
Available at: www.truvadapreprems.com/truvadaprep-resources
Truvada Package Insert:
Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2013/021752s042lbl.pdf
AIDS Vaccine Advocacy Coalition (AVAC) website: Pre-Exposure Prophylaxis
PrEP Watch: www.prepwatch.org/
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APPENDIX A. RESULTS FROM CLINICAL TRIALS OF THE EFFICACY OF DAILY ORAL PrEP FOR PREVENTING HIV INFECTION
APPENDIX B. HIRI-MSM RISK INDEX
APPENDIX C. AIDS INSTITUTE-FUNDED HIV PREVENTION COUNSELING PROGRAMS
The following link contains information about how to contact an AIDS Institute-funded HIV prevention program that provides risk-reduction counseling: