New PEP resource from the Health Protection Agency

The UK’s Health Protection Agency launched web pages offering guidance on occupational exposure to blood-borne viruses in healthcare workers in January 2003.

The web page address is http://www.hpa.org.uk/infections/topics_az/hiv_and_sti/hiv/occupational.htm

The pages offer links to key guidance documents on occupational exposure issued by the UK Department of Health and other regulatory bodies.

Information on HIV, hepatitis B and hepatitis C is included in the web pages, and a poster What to do if exposed can be downloaded from the site. Data collected by the Communicable Diseases Surveillance Unit on occupational exposure to blood-borne viruses such as HIV are also available.

PEP for needlestick injuries

The risk of contracting HIV following occupational exposure to HIV is low. Epidemiological studies have indicated that the average risk of HIV transmission after percutaneous (passing through the skin) exposure to HIV infected blood in health care settings is about 3 per 1,000 injuries.

Following a mucocutaneous (via the mucous membrane) exposure the average risk is estimated to be less than 1 in 1,000.

Where intact skin is exposed to HIV infected blood, no risk of HIV transmission is considered.

A case control study amongst health care workers exposed to HIV has found that the administration of AZT for four weeks after exposure was associated with an 80% reduced risk of seroconversion.

AZT treatment at this stage is believed to block the infection of immune system cells by HIV, so prompt AZT treatment is likely to block the establishment of HIV infection in an individual who has been exposed to the virus.

It is assumed that a combination of two or three drugs may be even more effective than AZT at blocking HIV infection.

On the basis of these findings, US health authorities have recommended that healthcare workers who suffer certain types of injuries should be offered post–exposure prophylaxis with a combination of two or three drugs.

Those who received a deep injury from large diameter needle previously inserted in the veins of a patient with high viral load and/or advanced AIDS will be recommended to commence a combination of AZT, 3TC and indinavir or nelfinavir immediately. A three-drug combination is recommended in these circumstances because the risk of seroconversion is judged to be high.

Despite the benefits of PEP there is evidence that the standard regimen of AZT/3TC/indinavir is poorly tolerated. Nine of 18 healthcare workers at three London hospitals who commenced this regimen stopped or changed therapy due to side effects within four weeks. Six of the 19 who started indinavir required more than two weeks off work; among the other 9 only one required more than 7 days' leave. There were no discontinuations among the five people who received saquinavir (Parkin).

Since the publication of the guidelines in 1998, according to the updated 2001 guidelines,

“Efavirenz, abacavir, and lopinavir/r (Kaletra) a PI, have been approved by FDA. Although side effects might be common with the NNRTIs, Efavirenz might be considered for expanded PEP regimens, especially when resistance to PIs in the source person's virus is known or suspected. Abacavir has been associated with dangerous hypersensitivity reactions but, with careful monitoring, may be considered as a third drug for PEP. Kaletra, a combination of lopinavir and ritonavir, is a potent HIV inhibitor that, with expert consultation, may be considered in an expanded PEP regimen.”

The 2001 guidelines were published before tenofovir became available. Protease inhibitors alone are not to be recommended as they only work after HIV has become integrated into the genome; they prevent viral proliferation but not necessarily infection.

Those who suffer blood splashes or other injuries may be offered a three–drug combination if the injury is extensive or the exposure prolonged. Otherwise, healthcare workers will usually be offered a combination of AZT and 3TC or tenofovir and 3TC/FTC.

It is recommended that post–exposure prophylaxis commence within 24 – 36 hours of injury, and preferably within a few hours of exposure.

UK guidelines issued by the Expert Advisory group on AIDS and the Department of Health recommend PEP be administered to health care workers if they have had a significant occupational exposure to blood or another high risk body fluid from a patient or other source either known to be HIV-positive, or considered to be at high risk of HIV infection, but where the result of an HIV test has not or cannot be obtained, for whatever reason.

Current UK practice

A telephone survey of 26 surgeons working in 13 hospitals in the South West of England found that only 8 out of 26 were aware of DoH guidance in September 1998, and only two out of 26 were aware of local recommendations, such as where to go for out-of-hours PEP (Duff). These findings suggest poor communication of policies on occupational PEP within NHS Trusts.

The July 2000 edition of the DoH guidance states that every NHS Trust or other health care setting should develop a post-exposure policy and protocol. In addition, it recommends that starter packs should be available on site for use following occupational exposure.

Data collection

Surveillance on health care workers in England, Wales and Northern Ireland who have been exposed to blood-borne viruses has been carried out since 1984.

Over the five years from July 1997 to June 2002, 1550 initial reports of occupational exposures to one or more blood borne virus were received by HPA. Of these 509 healthcare workers (HCWs), regardless of source status were prescribed post-exposure prophylaxis (PEP). Overall hepatitis C virus (HCV) represented 49% of all reports, HIV 30%, and hepatitis B 13%, and PEP with unknown source 8%. Percutaneous injury was the most frequently reported exposure route accounting for 72% (n=1125). Hollow bore needles accounted for 47% (n=734) of all reports. Occupationally, nursing related professions accounted for 42%, with doctors accounting for 35% of all reports.

For six-week follow-up HPA received 1064 reports. The most commonly reported location of exposures incident remains the ward. Exposure events occurring after the procedure or during or after disposal accounted for 36%.

Percutaneous venepuncture remains the number one procedure reported, with suturing second. Contributing factors were reported in 35% (n=369) of reports. Patients moving or being agitated was the most frequent, followed by non-compliance with universal precautions.

Reported PEP regimes reflect those recommended by the HIV post-exposure prophylaxis: guidance from the UK chief medical officers' expert advisory group on AIDS. Where PEP was discontinued and the source status was HIV-positive, side-effects were the most frequent reported reason to stop. Overall the most frequently reported side-effect, regardless of source status, was gastro-intestinal disturbances. Where reported, PEP was commenced within an hour in 37% of HCWs prescribed PEP and 63% within two hours.

Follow-up is undertaken at six months for exposures to HIV and HCV. A total of 737 of these six- month reports were received by HPA. Over the five-year period, seroconversions in four HCWs have been identified through the surveillance. One HCW seroconverted to HIV, despite triple PEP. Three HCWs seroconverted to HCV (one, which occurred in 1996 retrospectively reported).

The use of nevirapine

Nevirapine has been proposed as a suitable drug for PEP because it causes less nausea and is less disruptive to everyday life than indinavir, one of the protease inhibitors currently recommended in UK guidelines. There is a growing body of evidence from the use of two-dose nevirapine treatments in preventing mother-to-child transmission which suggests that nevirapine can be both safe and effective.

However, a recent study found that the use of nevirapine for post-exposure prophylaxis as a four-week course of treatment may carry an unacceptable risk of serious adverse effects.

Between 1997 and 1999 Camden and Islington Health Authority used d4T/3TC and nevirapine as its standard PEP regimen.

Researchers from the Royal Free and University College Medical School recently published an analysis of PEP including nevirapine prescribed to exposed healthcare workers and attendees at a central London GUM clinic. Data were collected from the case notes of 57 individuals (40 men and 17 women) who received PEP between January 1997 and November 1999 (Benn).

Of the 57 individuals, 33 reported that they had completed a full 4-week course of PEP. Five individuals had a major adverse event; two had a grade four rise in concentrations of liver aminotransferases and three had a grade three rise in liver aminotransferases. In all five of the patients nevirapine therapy was stopped.   

A nevirapine-containing regimen was no better tolerated than an indinavir-containing regimen overall, although fewer minor adverse events were seen in the nevirapine group. The authors postulated that the study may have underestimated the occurrence of side-effects and overestimate tolerability due to the fact that only 41 of the 57 people who were prescribed PEP had any documented follow-up during the 4-week period on PEP.

The authors concluded that whilst there may be a biological argument for using a regimen that includes an NNRTI, the possible safety problems of such a regimen seen in their HIV-negative population might make alternative regimens preferable. One option might be to limit the nevirapine component to the first few days, but the impact of this on the incidence of side effects is unknown.

US authorities recently reported 22 cases of severe or life-threatening side-effects such as rash and liver failure among people taking nevirapine as post-exposure prophylaxis. Some experts have suggested the risk of severe toxicity means that nevirapine should not be recommended for PEP in this context.

The problem of tolerability

Antiretroviral regimens prescribed for established HIV infection can be difficult to tolerate, those used immediately after exposure (PEP) are no exception.

Side-effects experienced during the course of PEP can have a critical influence on whether or not an individual is able to complete the course, which in turn has implications for the likely effectiveness of a combination.

The Italian Post-Exposure Prophylaxis Registry to the end of 1999 included data from 647 healthcare workers whose PEP consisted solely of AZT, and 341 who had taken a triple combination (191 of whom received indinavir).

Researchers found no significant differences in the proportion of health-care workers experiencing side-effects, though 10.5% of healthcare workers who had been prescribed a triple combination including indinavir did discontinue the indinavir and remain on double nucleoside analogue therapy after a median of seven days of treatment.(Puro)

Other reports have suggested that a regimen which includes a protease inhibitor may be particularly hard to tolerate.

Protocols for managing PEP requests

Hospitals and other sites need to have protocols established in advance of any requests for post–exposure prophylaxis. Planners need to bear in mind:

• Confidentiality, both of the person who is exposed and of the patient or person who is the potential source of infection.
• Training on prevention of needle–stick injuries and post–exposure procedures, including AZT treatment.
• Speed of administration of PEP. It is assumed that PEP needs to be administered within 24 hours of exposure, and is most likely to be most efficacious if started within one hour of exposure.
• Counselling regarding the risks of seroconversion, the use of PEP, safer sex and other information on HIV transmission. Counselling should above all seek informed consent for the use of PEP and for post–exposure HIV testing. The worker should be informed of the diverse opinions amongst physicians regarding the post–exposure use of antiretrovirals. Further information on antiretrovirals is presented in the HIV & AIDS Treatments Directory, also published by NAM, and at aidsmap.com.
• Surveillance procedure, including recording of circumstances in which exposure occurred, dosage schedule, serological test results, reporting to relevant authorities.

PEP after sexual exposure

Further discussion of PEP after sexual exposure can be found in Developing prevention technologies.  Several portions of this section appeared previously as a National HIV Prevention Information Service briefing on post-exposure prophylaxis.

References

Banatvala JE et al: HIV Infection: Hazards of Transmission to Patients and Health Care Workers during Invasive Procedures, Royal College of Pathologists Working Group.

Bell D et al: Zidovudine use after occupational HIV exposure: toxicity and failures reported to the CDC, Ninth International Conference on AIDS, abstract  WS–C12–6, 1993.

Benn, P et al. Prophylaxis with a nevirapine-containing triple regimen after exposure to HIV-1. The Lancet, 357: 9257, 2001.

CDC: Public Health Service Statement on Management of Occupational Exposure to Human Immunodeficiency Virus, Including Considerations Regarding Zidovudine Postexposure Use, MMWR 39 Supp RR–1 Jan 26 1990.

CDC: Update: Provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV MMWR 45: 468–472.

CDR Weekly Communicable Disease Report, Volume 10: 33, 2000.

Centers for Disease Control and Prevention. Public Health Service Guidelines for the Management of Health care worker exposure to HIV and recommendations for post-exposure prophylaxis. MMWR 47 1998.

Duff SE et al. Surgeons' and occupational health departments' awareness of guidelines on post-exposure prophylaxis for staff exposed to HIV: a telephone survey. British Medical Journal 319: 162, 1999.

Henderson DK. Post-exposure chemoprohylaxis for occupational exposure to the human immunodeficiency virus. Journal of the American Medical Association, 281: 931-936, 1999.

HIV Post-Exposure Prophylaxis: Guidance from the UK Chief Medical Officers' Expert Advisory Group on AIDS. Department of Health. July 2000.

Parkin J et al. Tolerability and side-effects of post-exposure prophylaxis for HIV infection. The Lancet 355:  9205, 2001.

Puro V. Post exposure prophylaxis for HIV infection. The Lancet, 355: 9214, 2000.