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 iPrex

iPrex Study Results

Use the links below to access the New England Journal of Medicine iPrex study results article as well as PDF fact sheets from the global study coordinators.


Fact Sheets (English)

Fact Sheets (Spanish)

Fact Sheets (Portuguese)

 

Questions?   Email us at information@fenwayhealth.org.

Download a PDF of these guidelines here.

Download a PDF of the CDC's PrEP guidelines here.

Chemoprophylaxis To Prevent HIV Infection: An Interim Guidance for Clinicians

The New England Journal of Medicine published the results of an historic HIV prevention study on November 23, 2010: Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men by Grant et al. The study demonstrated that men who were assigned to take a combination antiretroviral medication orally on a daily basis decreased their HIV risk by almost half compared to those assigned to take a placebo.

As this is the first published study on this novel approach to HIV prevention, called PrEP (pre-exposure prophylaxis), using available oral medication it is likely that clinicians will be approached by patients requesting PrEP for HIV prevention. The Fenway Institute offers this information for clinicians to review the findings of the study and as interim guidance for prescribing and supporting patients seeking PrEP in advance of development of guidelines by any government agencies or professional societies.

Study Highlights:

  • The populations included in this study were HIV uninfected men who have sex with men (MSM) and Transgender women (MTF), at high risk for sexual exposure to HIV.
  • This was a double blind placebo controlled study in which participants were given a daily dose of either 200 mg of emtricitabine and 300mg of tenofovir disoproxil fumarate (FTC–TDF) as a single fixed dose combination pill, or placebo.
  • Subjects were followed monthly and received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections at each routine visit.
  • The results demonstrated the efficacy of daily use of medication in combination with monthly prevention counseling as noted above. Those taking daily FTC-TDF daily had a 44% lower rate of HIV infection than those in the placebo.  When looking at only those with a high adherence level (who reported at taking at least 90% of their medication, the protective effect exceeded 70%.  For those in whom medication was detected in their blood, risk of infection decreased by more than 90%.
  • While side effects were minimal, some on the study developed mild renal insufficiency which resolved when the medication was stopped in almost every case. Those in the treatment group also experienced mild nausea more frequently during the first four weeks of the trial.
  • There was a dramatic increase in efficacy when adherence was high, making ongoing discussion of adherence with patients using medication for prevention of great importance
  • Development of resistance among those taking the medication was low and limited to those who were HIV infected at the time the study began. No resistance to one of the active medications, tenofovir, was seen at any point in the trial. Nevertheless, the possibility of resistance to these medications or other related medications has to be considered, particularly if PrEP users are not fully adherent, continue to engage in sexually risky practices, and do not routinely undergo follow-up HIV testing.

Prescribing PREP- Interim Guidance for Providers

The following is meant to be used as a guide for initiation of PrEP and follow up in clinical practice. This guide is based on procedures and findings from the above noted study. 

  • PrEP may be considered for HIV-uninfected persons who engage in high risk sexual activities. This includes but is not limited to:  
    • Men who have sex with men (MSM) engaging in receptive anal intercourse (RAI) and/or insertive anal intercourse ( IAI) with multiple partners
    • Male-to-Female Transgender persons engaging in RAI and/or IAI with multiple partners
    • Homosexual serodiscordant couples who intend to have unprotected intercourse
    • MSM or TG MtoF with history of repeated sexually transmitted infections (STI), particularly those that suggest unprotected insertive or receptive anal sex
  • HIV Counseling and Testing should be conducted per CDC Guidelines prior to initiating PrEP. The use of viral load testing by PCR or bDNA  can facilitate the accurate determination of serostatus as HIV-infected patients should not receive PrEP, and should be offered highly active antiretroviral therapy (HAART), which generally consists of 3 active medications.
  • Discussion and counseling regarding drug and alcohol use.
  • STI screening considerations for asymptomatic individuals should include:
    • RPR (syphilis)
    • Gonorrhea and Chlamydia screening  at exposure sites (oral, anal, urethral)
    • Hepatitis B and/ or C serology.
    • Hepatitis B vaccination when indicated. .
  • PrEP Regimen:  Prescription for – FTC-TDF (200 mg of emtricitabine and 300mg of tenofovir disoproxil fumarate ), 1 tablet PO QD, 30 pills
  • PrEP prescriptions should be provided with adherence counseling. This is critical as the effectiveness of the intervention appears to be dependent on adherence to taking the medication.
  •  PrEP prescriptions should also be provided in conjunction with other known HIV Prevention messages;  counseling and testing, risk reduction counseling, condom education and distribution and STI counseling, testing and management.
  • All persons prescribed PrEP should be informed of the symptoms of an acute seroconversion reaction (ASR) and should be advised to seek immediate medical attention if they experience symptoms of ASR in context of a high risk exposure.
  • Review of potential drug interaction and side effects which may include:
    • Patients taking regular ASA or NSAIDS should have monthly evaluation fo renal toxicity including BUN and Creatinine.
    • Patients should be advised that they may experience mild transient nausea the first 4-8 weeks of being on FTC-TDF.
    • Patients  taking  immunomodulators should not be prescribed FTC-TDF for PrEP.

During the course of the IPREX study, participants were followed monthly, which will not be sustainable for the long term in routine practice. The following is meant as a guideline for follow-up once PREP is initiated and should be based on a patient’s individual risk patterns.

  • Adherence Counseling: For the first few months of the PrEP regimen, patients should be seen on a monthly basis to optimize adherence by increased engagement with the primary provider. After 3 months, if the patient is adherent, quarterly follow-up is reasonable.
  • Renal safety labs (BUN, Creatinine, Creatine Clearance) can be evaluated for early signs of nephrotoxicity monthly for three months.   After 3 months, if the patient does not demonstrate toxicity, quarterly follow-up is reasonable.  
  • Chronic Hepatitis B and PrEP (tenofovir and emtricitabine):  These products are active against Hepatitis B, which means that they can be used to help treat patients with chronic Hepatitis B. Liver function (AST, ALT, T Bili) should be monitored closely if Hepatitis B infected patients discontinue PrEP, since there is a potential for acute hepatitis. PrEP users who are intermittently adherent to the medication are at risk for developing drug-resistant Hepatitis B.
  • HIV counseling and Testing every 2-3 months
  • Evaluation and treatment for STI’s and referrals for partners to have evaluation as appropriate.
  • Screening asymptomatic individuals for STI’s as noted above.
  • At each follow-up visit, the provider should reassess the need for PrEP, since behaviors may change, and the patient may not subsequently need a new prescription. 

The cost of these medications in the United States is high (up to $10,000 per year). There is currently no information on coverage by insurance companies. Some may begin obtaining this on their own both in this country and from less expensive generic manufacturers abroad. Efficacy of these generic medications has not been studied. In general if made by a reputable company abroad, these medications have proven the equivalent of what can be purchased in the United States and are tested by the World Health Organization for equivalency. This availability does however suggest wide availability of these medications, and that physicians ask their patients if they are taking any medications which they have not prescribed and follow up appropriately.

Recognizing that the FDA has not been asked to consider use of FTC and TDF in this manner, use of FTC-TDF is considered off label use.  Pharmaceutical companies are not allowed to promote a drug for off label use. However, once a drug has been approved for sale for one purpose, physicians are free to prescribe it for any other purpose that in their professional judgment is both safe and effective, and are not limited to official, FDA-approved indications.

References

Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010. (10.1056/NEJMoa1011205)

CDC STD Treatment Guidelines 2010 ( http://www.cdc.gov/std/treatment/2010)

Dear Colleague Letter regarding PrEP from the Centers for Disease Control  (http://www.cdc.gov/hiv/ehap/resources/direct/112310/hcp.htm)

 

Guidelines updated January 28, 2011

 

 

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