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
Fact Sheets (English)
Fact Sheets (Spanish)
Fact Sheets (Portuguese)
Questions? Email us at email@example.com.
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
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.
- 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
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.
may be considered for HIV-uninfected persons who engage in high risk
sexual activities. This includes but is not limited to:
who have sex with men (MSM) engaging in receptive anal intercourse (RAI) and/or insertive anal intercourse ( IAI)
with multiple partners
Transgender persons engaging in RAI
and/or IAI with multiple partners
serodiscordant couples who intend to have unprotected intercourse
or TG MtoF with history of repeated sexually transmitted infections
(STI), particularly those that suggest unprotected insertive or receptive
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.
and counseling regarding drug and alcohol use.
screening considerations for asymptomatic individuals should include:
and Chlamydia screening at
exposure sites (oral, anal, urethral)
B and/ or C serology.
B vaccination when indicated. .
Regimen: Prescription for – FTC-TDF
(200 mg of emtricitabine and 300mg of tenofovir disoproxil fumarate ), 1
tablet PO QD, 30 pills
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
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
- Review of
potential drug interaction and side effects which may include:
taking regular ASA or NSAIDS should have monthly evaluation fo renal
toxicity including BUN and Creatinine.
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.
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.
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.
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
counseling and Testing every 2-3 months
and treatment for STI’s and referrals for partners to have evaluation as
asymptomatic individuals for STI’s as noted above.
each follow-up visit, the provider should reassess the need for PrEP,
since behaviors may change, and the patient may not subsequently need a
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.
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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