The rationale for post-exposure prophylaxis is set out in detail in the WHO guideline on PEP based on the pathogenesis of HIV infection, the biological plausibility that using antiretroviral drugs can prevent transmission and the risk and benefits of post-exposure prophylaxis to exposed healthcare workers.
The knowledge about primary HIV infection indicates that systemic infection does not occur immediately, leaving a brief "window of opportunity" during which post-exposure antiretroviral intervention may modify viral entry into cell and replication. Data from animal studies have been difficult to interpret due to a lack of a comparable animal model and the need to have a higher inoculum than that expected after exposure to needlestick injuries (CDC, 1998). However animal studies have demonstrated that early initiation of post-exposure prophylaxis and small inoculum size correlates with successful post-exposure prophylaxis.
No randomized clinical trials have evaluated the efficacy of post-exposure prophylaxis in humans. In a retrospective case control study among healthcare workers, the risk for HIV infection in those who used zidovudine as post-exposure prophylaxis was reduced by 81%.
Herida et al. (2006) concluded that, in France, for the efficient use of public health resources, PEP use should target high-risk exposure events. To achieve this goal, national guidelines should provide more precise treatment indications, taking into account the type of exposure and the sero-status of the source. They noted that this would relieve the pressure from clinicians to prescribe PEP to individuals with a very low risk of HIV infection, however, correctly, stressed that to avoid apparent contradiction with current HIV prevention messages, PEP guidelines must be revised by consensus with the health authorities, physicians and patients' organizations involved in HIV prevention.
Young et al. (2007) undertook a systematic review of the literature to evaluate the effects of antiretroviral PEP post-occupational exposure to HIV. They concluded that the use of occupational PEP is based on limited direct evidence of effect. However, it is highly unlikely that a definitive placebo-controlled trial will ever be conducted, and, therefore, on the basis of results from a single case-control study, a four-week regimen of PEP should be initiated as soon as possible after exposure, depending on the risk of seroconversion. There is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV. However, due to the success of combination therapies in treating HIV-infected individuals, a combination of antiretroviral drugs should be used for PEP. Healthcare workers should be counselled about expected adverse events and the strategies for managing these. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion.
As noted above, a randomized controlled clinical trial is neither ethical nor practical. Due to the low risk of HIV seroconversion, a very large sample size would be required to have enough power to show an effect. More rigorous evaluation of adverse events, especially in the developing world, is required.
Van Oosterhout et al. (2007) set up a PEP programme in Malawi for healthcare workers exposed to BBF at work. After the first year of their programme as well as interviews with programme participants they made the following recommendations for the introduction of HIV PEP in resource poor settings: (a) an intensive and continuous publicity campaign is required; a PEP management team in which all the potential benefiting groups are represented should be established, as this is likely to improve ownership and uptake of the programme. (b) Emphasis needs to be given to the value of reporting post-PEP-HIV test results back to the clinician, to advise clients in case of HIV transmission and to properly evaluate the effectiveness of the PEP strategy. (c) Where the incidence of occupational injuries is high, injury-prevention measures need to be reviewed. (d) In many developing countries, hepatitis B prevalence among hospital patients is very high and, since the infectivity of hepatitis B is far higher than that of HIV, routine hepatitis B vaccination should be available for all nursing and clinical staff., and (e) A PEP programme can be used as a tool to focus attention on other aspects of HIV infection to staff members of healthcare institutions, such as voluntary counselling and testing.
PEP is not without side-effects such as nausea and vomiting, fatigue, influenza-like illness, rash, unpleasant taste in the mouth, headache, reflux, and dysuria, thus education, training and follow-up is required to ensure all workers are aware of the risks and benefits of treatment.
The study conducted by Taegtmeyer and colleagues in Kenya (2008) explored the knowledge, attitudes, and practice of post-exposure prophylaxis among healthcare workers. This 5-year study revealed that uptake of PEP was low at only 4% of those who had needlestick injuries in the study population. In-depth interviews revealed this was due to healthcare workers fear of HIV testing and their perception of needlestick injuries as low risk. The authors concluded post-exposure prophylaxis can be made readily available in most Kenyan districts. However, where HIV testing remains stigmatized uptake will be limited- particularly in the initial phases of a programme.
O'Malley et al. (2007) undertook a convenience sample of four healthcare facilities to determine the cost of management of occupational exposures to blood and body fluids. They collected detailed information on time spent reporting, managing, and following up the exposures; salaries (including benefits) for representative staff who sustained and who managed exposures; and costs (not charges) for laboratory testing of exposure sources and exposed healthcare personnel, as well as any post-exposure prophylaxis taken by the exposed personnel. They analyzed data for 31 exposure scenarios and found that the overall range of costs to manage reported exposures was $71-$4,838. Mean total costs varied greatly by the infection status of the source patient. The overall mean cost for exposures to human immunodeficiency virus (HIV)-infected source patients (including those co-infected with hepatitis B or C virus) was $2,456 (range, $907-$4,838), whereas the overall mean cost for exposures to source patients with unknown or negative infection status was $376 (range, $71-$860).
The 5-country study by Corbett confirmed that PEP use was not well-understood and there are gaps in implementation.
One study examined in the review by IPPF, UCSF, UNAIDS, UNFPA, WHO 2008 found that when the clinic progressively integrated a variety of sexual and reproductive and primary health care services, including TB services, nutritional support for families affected by HIV, prenatal services for pregnant women living with HIV, post-rape services (including counselling and PEP for health care-workers), the number of clients being tested for HIV increased dramatically.
• The various documents reviewed seem to increasingly mention the importance of including sexual and reproductive health issues in programmes aimed at offering health worker access to HIV/TB prevention and care services. As noted in the existing guidelines, (ILO/WHO PEP guidelines, 2008) when providing ART PEP for occupational exposure, it is necessary to also counsel the worker on the practice of safer sex until follow up tests return negative. These guidelines also note that inclusion of sexual and reproductive health issues in PEP programmes also enables HIV positive health workers to effectively manage their illness, opportunistic infections, family planning and their families' risk of transmission.
Thus world consensus remains that PEP should be made available to all health workers, and the appropriate use of PEP needs to be strengthened, including ensuring that workers understand the benefits and risks.
The GG emphasizes that there needs to be:
- Improved advocacy and policy dissemination for PEP.
- Improve awareness and training amongst health workers by providing ongoing education and evaluation.
- Protocols organized for risk evaluation and PEP procedures.
- A trained focal person at each facility.
- Assurance that PEP is available during and after normal working hours.
- Strengthened reporting by ensuring all staff understand the importance of monitoring and potential benefits.
- Confidentiality in providing PEP
- Components of sexual and reproductive health within PEP counselling.