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Guideline Summary
Guideline Title
Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men.
Bibliographic Source(s)
Centers for Disease Control and Prevention (CDC). Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR Morb Mortal Wkly Rep. 2011 Jan 28;60(3):65-8. [10 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Human immunodeficiency virus (HIV) infection

Guideline Category
Counseling
Prevention
Risk Assessment
Clinical Specialty
Family Practice
Infectious Diseases
Internal Medicine
Preventive Medicine
Intended Users
Advanced Practice Nurses
Health Care Providers
Physician Assistants
Physicians
Public Health Departments
Guideline Objective(s)

To provide interim guidance for health-care providers in the United States based on results of the only large clinical trial testing the efficacy and safety of preexposure prophylaxis (PrEP) for reducing human immunodeficiency virus (HIV) acquisition by men who have sex with men (MSM)

Target Population

Adult men who have sex with men (MSM) and who are at high risk for sexual acquisition of human immunodeficiency virus (HIV)

Interventions and Practices Considered
  1. Determining eligibility for preexposure prophylaxis (PrEP) medication
    • Documenting negative human immunodeficiency virus (HIV) antibody test
    • Testing for acute HIV infection
    • Confirming high risk for HIV infection
    • Linking HIV-infected partners to care
    • Calculation of creatinine clearance
  2. Screening for hepatitis B infection and treating active hepatitis B infection
  3. Vaccination against hepatitis B infection
  4. Treating other sexually transmitted infections
  5. Beginning PrEP medication regimen (tenofovir disoproxil fumarate 300 mg plus emtricitabine 200 mg [i.e., one Truvada tablet] daily)
  6. Providing risk-reduction and PrEP medication–adherence counseling and condoms
  7. Follow-up while PrEP medication is being taken
  8. Discontinuing PrEP (at patient request, for safety concerns, or if HIV infection is acquired)
Major Outcomes Considered
  • Risk for human immunodeficiency virus (HIV) acquisition
  • Rate of acquisition of HIV infection among uninfected but exposed men who have sex with men (MSM)
  • Safety and effectiveness of preexposure prophylaxis (PrEP)
  • Medication adherence

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Searches of Patient Registry Data
Description of Methods Used to Collect/Select the Evidence

The evidence base for these recommendations is derived from a systematic search and review of published literature. To identify all preexposure prophylaxis (PrEP) safety and efficacy trials pertaining to prevention of sexual acquisition of human immunodeficiency virus (HIV), a search of the clinical trials registry (www.clinicaltrials.gov External Web Site Policy) was performed using combinations search terms (preexposure prophylaxis, pre-exposure prophylaxis, PrEP, HIV, Truvada, Tenofovir, and antiretroviral). In addition, the same search terms were used to search conference abstracts for major HIV conferences (annual International AIDS Society Conference, annual Conference on Retroviruses and Opportunistic Infections) for the years 2009-2010. Using the same search terms, a search of PubMed and Web of Science databases was done for the years 2006-2010. Finally, references from published PrEP trial data were reviewed and the data summary prepared by Food and Drug Administration (FDA) for its approval decision, and both confirmed no additional trial results were available.

Number of Source Documents

One multinational, randomized, double-blind, placebo-controlled, phase III clinical trial

Methods Used to Assess the Quality and Strength of the Evidence
Not stated
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Systematic Review
Description of the Methods Used to Analyze the Evidence

The Pre-Exposure Prophylaxis Initiative (iPrEX) is a multinational, randomized, double-blind, placebo-controlled, phase III clinical trial of daily oral antiretrovirals (tenofovir disoproxil fumarate [TDF] and emtricitabine [FTC]) to prevent acquisition of human immunodeficiency virus (HIV) infection among uninfected but exposed men who have sex with men (MSM). Data from the trial were analyzed from visits through May 1, 2010, for 2,499 enrolled participants (including 29 male-to-female transgender persons) in the modified "intent to treat" analysis (excluding 10 participants found to be HIV-infected at enrollment and 48 who did not have an HIV test after enrollment), 36 of 1,224 participants in the preexposure prophylaxis (PrEP) arm and 64 of 1,217 participants in the placebo arm who were followed for acquisition of HIV infection.

Methods Used to Formulate the Recommendations
Expert Consensus
Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
Not stated
Description of Method of Guideline Validation

Not applicable

Recommendations

Major Recommendations

Centers for Disease Control and Prevention (CDC) and other U.S. Public Health Service (PHS) agencies have begun to develop PHS guidelines on the use of preexposure prophylaxis (PrEP) for men who have sex with men (MSM) at high risk for human immunodeficiency virus (HIV) acquisition in the United States as part of a comprehensive set of HIV prevention services. Completing the guidelines and obtaining expert input and public comment will take several months before they can be published. Concerns exist that without early guidance, various unsafe and potentially less effective PrEP-related practices could develop among health-care providers and MSM beginning to use PrEP in the coming weeks and months. These concerns include 1) use of other antiretrovirals than those so far proven safe for uninfected persons (e.g., more than two drugs or protease inhibitors); 2) use of dosing schedules of unproven efficacy (e.g., "intermittent" dosing just before and/or after sex); 3) not screening for acute infection before beginning PrEP or long intervals without retesting for HIV infection; and 4) providing prescriptions without other HIV prevention support (e.g., condom access and risk-reduction counseling). Until the more detailed PHS guidelines are available, CDC is providing interim recommendations to help guide clinical practice.

CDC Interim Guidance for Health-Care Providers Electing to Provide Preexposure Prophylaxis (PrEP) for the Prevention of Human Immunodeficiency Virus (HIV) Infection in Adult Men Who Have Sex With Men and Who Are at High Risk for Sexual Acquisition of HIV

Before Initiating PrEP

Determine Eligibility

  • Document negative HIV antibody test(s) immediately before starting PrEP medication.
  • Test for acute HIV infection if patient has symptoms consistent with acute HIV infection.
  • Confirm that patient is at substantial, ongoing, high risk for acquiring HIV infection.
  • Confirm that calculated creatinine clearance is ≥60 mL per minute (via Cockcroft-Gault formula).

Other Recommended Actions

  • Screen for hepatitis B infection; vaccinate against hepatitis B if susceptible, or treat if active infection exists, regardless of decision about prescribing PrEP.
  • Screen and treat as needed for sexually transmitted infections (STIs).

Beginning PrEP Medication Regimen

  • Prescribe 1 tablet of Truvada (tenofovir disoproxil fumarate [TDF] [300 mg] plus emtricitabine [FTC] [200 mg]) daily. (These recommendations do not reflect current Food and Drug Administration-approved labeling for TDF/FTC.)
  • In general, prescribe no more than a 90-day supply, renewable only after HIV testing confirms that patient remains HIV-uninfected.
  • If active hepatitis B infection is diagnosed, consider using TDF/FTC for both treatment of active hepatitis B infection and HIV prevention.
  • Provide risk-reduction and PrEP medication adherence counseling and condoms.

Follow-up While PrEP Medication Is Being Taken

  • Every 2 to 3 months, perform an HIV antibody test; document negative result.
  • Evaluate and support PrEP medication adherence at each follow-up visit, more often if inconsistent adherence is identified.
  • Every 2 to 3 months, assess risk behaviors and provide risk-reduction counseling and condoms. Assess STI symptoms and, if present, test and treat for STI as needed.
  • Every 6 months, test for STI even if patient is asymptomatic, and treat as needed.
  • Three months after initiation, then yearly while on PrEP medication, check blood urea nitrogen and serum creatinine.

On Discontinuing PrEP (at Patient Request, for Safety Concerns, or If HIV Infection Is Acquired)

  • Perform HIV test(s) to confirm whether HIV infection has occurred.
  • If HIV positive, order and document results of resistance testing and establish linkage to HIV care.
  • If HIV negative, establish linkage to risk-reduction support services as indicated.
  • If active hepatitis B is diagnosed at initiation of PrEP, consider appropriate medication for continued treatment of hepatitis B.
Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

Recommendations are supported chiefly by data from a multinational, randomized, double-blind, placebo-controlled, phase III clinical trial.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate use of preexposure prophylaxis (PrEP) in reducing human immunodeficiency virus (HIV) acquisition among men who have sex with men (MSM), appropriate regular monitoring of HIV status, and ongoing risk-reduction and PrEP medication adherence counseling

Potential Harms

In the Pre-Exposure Prophylaxis Initiative (iPrEX) study, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) generally was well tolerated, although nausea in the first month was more common among those taking medication than among those on placebo (9% versus 5%). No differences in severe (grade 3) or life-threatening (grade 4) laboratory abnormalities were observed between the active and placebo arms, and no drug-resistant virus was found in the 100 participants infected after enrollment.

Qualifying Statements

Qualifying Statements
  • The findings in this report are subject to at least five limitations. First, the trial (Pre-Exposure Prophylaxis Initiative [iPrEX] study) was not large enough to evaluate efficacy in each of the sites, and the majority of the participants were in South America; only 10% were in the United States, making it impossible to determine effects on incidence in the United States trial sites specifically. Second, the assessment of adherence by drug-level testing was not performed for all trial participants and was performed for seroconverters at the first clinical visit in which infection was diagnosed; therefore, the findings might not reflect drug levels at the time of infection. Third, the study does not provide information about long-term health effects of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) in human immunodeficiency virus (HIV)-uninfected men or men who became HIV-infected while on preexposure prophylaxis (PrEP) medications. Fourth, results of drug-level testing showed that adherence measures in the trial might overstate levels of actual adherence; many of those with high levels of adherence to the daily regimen by self-report, pill count, and bottles dispensed had low levels or no drug measured in their blood. Finally, sexual risk behavior and adherence to PrEP medications among men who have sex with men (MSM) taking TDF/FTC for PrEP outside of a trial setting, and with awareness of trial results, might be different from what was observed for men in the iPrEx trial.
  • Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
  • References to non-Centers for Disease Control and Prevention (CDC) sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the U.S. Department of Health and Human Services. CDC is not responsible for the content of these sites. URL addresses listed in MMWR were current as of the date of publication.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Resources
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
Centers for Disease Control and Prevention (CDC). Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR Morb Mortal Wkly Rep. 2011 Jan 28;60(3):65-8. [10 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2011 Jan 28
Guideline Developer(s)
Centers for Disease Control and Prevention - Federal Government Agency [U.S.]
Source(s) of Funding

United States Government

Guideline Committee

Not stated

Composition of Group That Authored the Guideline

Authors: DK Smith, MD; RM Grant, MD; PJ Weidle, PharmD; A Lansky, PhD; J Mermin, MD; KA Fenton, MD, PhD, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available from the Centers for Disease Control and Prevention (CDC) Web site External Web Site Policy.

Print copies: Available from the Centers for Disease Control and Prevention, MMWR, Atlanta, GA 30333. Additional copies can be purchased from the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402-9325; (202) 783-3238.

Availability of Companion Documents

The following is available:

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on May 3, 2013.

Copyright Statement

No copyright restrictions apply.

Disclaimer

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