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HIV Medicine 2007
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31. Post-Exposure Prophylaxis (PEP)
HIV is not a very contagious pathogen. The transmission rate after contact is about 1:1000 to 1:100. Compared with HIV, the transmission rate for hepatitis C is 10 times higher, and 100 times higher for hepatitis B. Factors for the probability of transmission are the amount of incorporated virus and the exposure time. Contact with body fluids of a patient with a high viral load supposably holds a higher risk of contagion than a similar contact with body fluids of a patient under HAART with a suppressed viral load. Additionally, quick removal of infectious material e.g. from damaged skin or mucosal membrane by washing or disinfection presumably decreases the risk of an HIV infection. For percutaneous contact with HIV-containing blood, an infectiousness of 0.3 % in total is assumed. According to retrospective data, calculations have been established to assess the transmission risks of accidental exposure more precisely (see Table 1).
Table 1: Calculations to assess estimated individual transmission risk after HIV exposure *
Type of Exposure Relative Risk
Deep needlestick injury or cut 16 : 1
Fresh blood on the penetrating instrument 5 : 1
Penetrating needle previously placed in blood vessel 5 : 1
Source person with high viral load 6 : 1
Exposition of mucosal membrane 1 : 10
Exposition of inflammatory damaged skin 1 : 10
* Source: German-Austrian recommendations for Post-Exposure Prophylaxis against HIV infection 2004
Table 2 provides information about the assumed transmission risk of other types of exposure to HIV,
for example unsafe sexual contact. Since only few data exist, these risk estimates vary enormously
and should be judged with caution.
Table 2: HIV transmission risk for unprotected sexual contacts *
Type of unprotected contact Transmission risk per contact
Receptive anal sex with HIV- infected person 0.82 % (0.24 - 2.76)
Receptive anal sex with person of unknown HIV status 0.27 % (0.06 - 0.49)
Insertive anal sex with person of unknown HIV status 0.06 % (0.02 - 0.19)
Receptive vaginal sex 0.05 - 0.15 %
Insertive vaginal sex 0.03 - 5.6 %
Oral sex Probability unknown, single cases have been reported, particularly with incorporation of
semen in the mouth.
* Source: German-Austrian PEP recommendations 2004
In primary HIV infection the establishment of the virus in various tissue reservoirs does not occur
immediately after incorporation of the virus. Within a small time frame the establishment of the
virus might be prevented by post-expositional intervention.
Simian models show that in mucosal membranes HIV primarily infects the local immunocompetent cells
such as Langhans' cells. These cells or their siblings migrate to regional lymph nodes: detection of
HIV in the blood occurs days later. The process of local infection and migration of the cells to the
lymph nodes takes approximately 24 to 48 hours (Spira 1996, Otten 2000). Theoretically, treatment
with appropriate substances may avert a systemic infection.
Effectiveness and limitations of PEP
Early reports on the use of AZT after occupational needlestick injuries date from 1989. An analysis
of retrospective case-control studies shows that even prophylaxis with a single substance after
exposure reduces the probability of an infection by approximately 80 % (Tokars 1993). The
combination of multiple drugs is supposedly even more potent. Unfortunately there have been
transmissions despite the use of PEP. Transmission of HIV infection cannot always be prevented. Many
of the described cases of PEP failure were treated with AZT mono-prophylaxis. But there are also
reports about failures of antiretroviral combination therapies.
With increasing prevalence of resistance under antiretroviral therapy future problems might arise
with transmission of resistant virus strains. International surveillance studies report increasing
transmissions rates of mutant viruses. But, what to do is still unclear: resistance testing takes
days or more. So results would be too late to avoid spread of resistant viruses using appropriate
When is PEP indicated?
The indication to provide a PEP should be considered by a physician experienced in HIV treatment. It
is important to ascertain whether the source person has a supposed or confirmed HIV infection.
Unclear HIV status should be clarified: the source person should be asked for consent to perform HIV
testing. But denial of consent has to be respected. If the source person agrees to be tested, it
should be performed immediately. For source persons with confirmed HIV infection, the actual HIV
viral load, stage of disease, former and current HAART have to be taken into consideration.
Optimally, a resistance analysis would also be available (Puro 2003). The affected person should be
asked about the first aid procedures that have already been performed.
After clarification of these queries, the exposed person has to be informed about possible risks of
pharmaceutical PEP. It should be emphasized that none of the administered substances is approved for
use in this special setting. This is also important with regard to the coverage of cost, especially
for sexual exposure. The medication cannot be prescribed at the expense of the health insurance. PEP
for occupational exposure is usually covered by statutory accident insurance (in Germany).
Table 3 gives an overview of situations in which PEP is recommended according to current guidelines.
This serves as an orientation, although deviations may be necessary in individual cases.
Potential risks of PEP
The risks of PEP mainly concern the adverse effects of the antiretroviral substances, most
frequently gastrointestinal symptoms such as nausea, vomiting or diarrhea. Changes of hematology,
transaminases or creatinine are also possible. Additionally, there have been reports of elevated
triglycerides and cholesterol levels, and insulin resistance even in short term use of protease
inhibitors (Parkin 2000).
It is unknown whether the temporary use of antiretroviral substances may lead to long term side
effects, but this seems to be secondary since the main emphasis is to prevent a chronic and
potentially life-threatening disease. For pregnant women particular caution is required since data
concerning teratogenicity are lacking.
Table 3: Overview of recommendations for usage of PEP
· Percutaneous needlestick injury with hollow needle (body fluids with high viral load: blood,
liquor, material from biopsies, cultured virus)
Deep injury (e.g. cuts), apparently blood stained
Needle used before for intravenous injection Recommended
· Superficial injury (e.g. with surgical needle)
Where required, exemption, if source person has AIDS or high viral load Considered
· Contact of mucosal membrane or damaged skin with fluids with high viral load Considered
· Percutaneous contact with body fluids other than blood (e.g. urine, saliva) Not Recommended
· Contact of intact skin with blood (including high viral load) Not Recommended
· Contact of skin or mucosal membranes with body fluids such as urine or saliva Not Recommended
· Transfusion of HIV containing blood products (or if HIV contamination is highly probable)
· Unprotected receptive sex with an HIV-infected person Recommended
· IDU sharing contaminated needle or equipment Recommended
· Unprotected receptive oral sex with ejaculation with an HIV-infected person Considered
· Kissing and other sexual contacts without semen-/blood-mucosal membrane contact Not Recommended
· Accidental needlestick injury Not Recommended
Sources: CDC Guidelines for the management of occupational exposure to HIV 2005; UK guidelines for
the use of posr-exposure prophylaxis for HIV following sexual exposure 2006
According to actual guidelines, depending on the type of exposure, different procedures are
recommended following HIV-exposure. Following needlestick or cut injuries with HIV-contaminated
instruments, fluid should be expressed by squeezing the tissue surrounding the wound and striking
out proximal blood vessels towards the wound. Too intense massage or contusions have to be avoided.
The wound should be flushed with an alcoholic, virucidal antiseptic for a minimum of 10 minutes. For
skin that has been in contact with blood or body fluids removal of the infectious material and
subsequent extensive disinfection with a skin antiseptic appears sufficient. After contamination of
an eye, immediate flush with PVP iodine solution 2.5 % is recommended. If such a solution is not
available the eye should be washed with water. The oral cavity should be washed several times (about
10-15 seconds each) with an aqueous solution or preferably 80 % alcohol after contact with
potentially infectious material.
Needlestick or cut injury Contamination of damaged skin, eye or oral cavity
Expressing fluid by squeezing the tissue surrounding the wound (³ 1 minute) Intensive
washing with easily accessible liquid: high proof alcohol (undenaturated for the oral cavity), water
or isotonic saline solution, possibly PVP iodine solution
Intensive antiseptic washing or application of an antiseptic depot of antiviral agent
Figure 1: Recommended initial interventions after HIV exposure (Source: German-Austrian
recommendations for Post-Exposure Prophylaxis against HIV infection 2004)
Persons, who, through sexual exposure, have contact of anal or genital mucosae to infectious
material, should wash the penis with soap and water; genital mucosae should be flushed with water
after urination, which might wash contaminated material from the urethra. Intense washing of the
vagina or intestines is not recommended due to an elevated risk of injuries.
After these initial interventions, an expert in HIV treatment and antiretroviral therapy should be
consulted for the decision whether pharmaceutical PEP needs to be started.
Accurate evaluation and documentation of the course of the accident is very important, especially
for occupational exposure. The process of informing the patient about the risks of PEP needs to be
documented carefully and the patient should sign an informed consent.
Initiation of PEP
Time is the most important factor for initiation of PEP. The best chance to prevent transmission is
within the first 24 hours of exposure. After that time period, the risk of systemic spread of the
virus increases. Initiating PEP after more than 72 hours following exposure does not seem
PEP should be initiated as soon as possible, preferably within 2 hours of exposure.
If, in this short time frame, consultation with a physician experienced in HIV treatment is not
possible, it might be advantageous to just initiate PEP. Interrupting a regimen that isn't indicated
is always an option.
Actual recommendations prefer a regimen with a combination of antiretroviral substances given over 4
weeks, preferably consisting of two NRTIs and one PI (see Table 5). NNRTIs, especially nevirapine,
should not be used for PEP because of the risk of severe adverse effects (hepatotoxicity) (CDC
2001). For efavirenz such severe adverse effects have not been reported but the impact on the CNS,
particularly in the first weeks of intake, limits its use for PEP.
As far as possible, known resistance against antiretroviral substances of the source person should
be taken into account; in many cases, this information will not be available. Therefore use of
standard regimens for PEP has proven practical. Recommended combinations are shown in Table 5.
To remark: Except Nelfinavir all protease inhibitors are recommended to be used boosted with
In addition, since 2003, the fusion inhibitor T-20 (Fuzeon™) has been approved for HIV therapy.
Other substances, such as attachment inhibitors or coreceptor antagonists are under investigation.
These new substances with their mechanism to inhibit viral cell entry might also be interesting with
regard to increasing efficiency of PEP. Focusing on enfuvirtide, the subcutaneous route of
application and high costs currently prevent its routine use.
Furthermore, difficulties in monitoring a possible seroconversion might occur as development of
antibodies against enfuvirtide may lead to cross reaction with gp41 and a positive result in the
During pregnancy, PEP should only be used after careful consideration of the benefits since there
are only limited data on teratogenic effects. In any case, advice of a physician experienced in HIV
treatment and pregnancies should be obtained.
After contact with potentially infectious material, not only HIV, but also other diseases might be
transmitted. Apart from HIV, testing should be performed for hepatitis B and C. Persons exposed to
HBV should receive hepatitis B immunoglobulin and a vaccine series simultaneously if they have no
sufficient vaccination status.
Table 4: Recommended antiretroviral combinations for HIV Post-exposure Prophylaxis *
1. AZT + 3TC (Combivir™)
2. TDF + FTC (Truvada™)
3. TDF + 3TC (Viread™+Epivir™)
4. d4t + 3TC (Zerit™+ Epivir™)
Fosamprenavir (Lexiva™ or Telzir™)
* Sources: CDC Guidelines for the management of occupational exposure to HIV 2005; UK guidelines for
the use of posr-exposure prophylaxis for HIV following sexual exposure 2006
After unprotected sexual contacts, transmissions of other STDs such as syphilis or gonorrhea should
be taken into consideration. Testing is recommended at 2 and 4 weeks after exposure.
Management of PEP
After initiation of PEP, the patient should not be discharged without a follow-up consultation.
Persons exposed to HIV are under high psychological pressure. It is important to accompany the
patiens and to emphasize the generally low risk of transmission but not to dramatize the situation.
Adverse effects generally include gastrointestinal symptoms. Less frequent are changes in
hematology, liver enzymes or creatinine. These should be tested after 14 days and at the end of the
PEP. Despite close monitoring, different studies report discontinuation rates of 40-50 %. At the end
of a completed course or discontinued PEP, HIV testing should be performed after 6 weeks, 3 and 6
months. An HIV PCR only needs to be performed if there is reasonable suspicion of a primary HIV
In any case, the patient has to be advised to practice safer sex until a reliable negative test
result is achieved.
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