Post-exposure prophylaxis

Gus Cairns

Post-exposure prophylaxis (PEP) has been in use, initially primarily for healthcare workers, since 1988.1

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

Healthcare workers who may have been accidentally exposed to HIV-infected body fluids (for example through injury with a contaminated syringe) are offered a one-month course of antiretroviral drugs. Increasingly, people who are exposed to HIV outside the workplace, through sex and needle-sharing, are also seeking out and obtaining PEP.

PEP has never been subject to a randomised controlled trial as it would be unethical to offer placebo treatment, or none, to someone exposed to HIV. In addition, over a limited period of time, events that are known to involve a maximal exposure to HIV, and transmission during those events, are comparatively rare, even in a high-risk population.

For these reasons it is hard to say what would have happened if people had not taken PEP. A very large trial would be needed to demonstrate the effectiveness of PEP. However a 1997 case control study2 of healthcare workers from France, Italy, the UK, and the US came to the conclusion that PEP – in this case AZT (zidovudine, Retrovir) monotherapy – reduced the risk of becoming infected with HIV by 81% (with a confidence interval of 48-94%). This was equivalent to reducing the risk of infection from 1 in 200 to 1 in 10,000.

Providing PEP after exposure through sex (PEPSE) or, to use a more general term, which includes parenteral exposure, ‘non-occupational PEP’ (NONOPEP), has taken longer to become accepted and to be provided. Resistance to the idea of the widespread provision of PEP has been based on arguments about its expense and cost-effectiveness, whether its provision would cause increases in risk behaviour, and lack of effectiveness on a population level.

In fact PEP tends to be used comparatively rarely. This may be because obtaining PEP is inevitably time-consuming and often difficult, because people often do not know they have been at risk or believe they have not been, and because there is at most a 72-hour period after exposure to HIV during which PEP is recommended.

There is little evidence that the provision of PEP contributes significantly to risk behaviour.

Although, for these reasons, PEP is unlikely ever to make a significant contribution to the reduction of HIV incidence and prevalence, it is clearly efficacious on the individual level and there is a strong human rights argument for its public provision, especially when it is already provided for occupational exposure.

A comparison of per-exposure risks suggests that unprotected receptive anal sex3 with an HIV-positive partner may be ten times as risky, in terms of the likelihood of infection from a single exposure, as a needlestick injury.4 And although a single needlestick injury may be a little bit riskier than a single act of receptive vaginal sex, factors such as high viral load or trauma during rape may make transmission more likely.5,6

One necessary precondition for a policy of offering PEP is the widespread availability of HIV testing, so that people considering taking PEP are sure that they are HIV-negative. This would be especially important if the treatment option provided were inappropriate for treating HIV-positive people, for example, short-course Combivir, a fixed-dose combination pill containing AZT and 3TC). It is also important, if at all possible, to ascertain the HIV status of the contact partner so that if they are found to be HIV-negative, PEP can be stopped.

When it is provided, research has shown that people use PEP inconsistently. Studies have found that many people who have sought and taken PEP have, within a few months or even while they are taking PEP, gone on to risk further exposures to HIV without seeking further PEP (see Putting PEP into practice). This is not an argument against the initial provision of PEP, but shows that people may be reluctant to admit further risk behaviour, may leave it too late to seek PEP on subsequent occasions, and are often bad at assessing the degree of risk they have been exposed to; they may form very different estimates of the riskiness of an incident even where external circumstances are the same.

Other factors that influence the decision to seek PEP may include:

  • whether the contact partner is known to be HIV positive,
  • whether the contact partner is judged to be a ‘high-risk’ person if their serostatus is unknown,
  • whether the contact partner recommended PEP,
  • whether the exposure was consensual or non-consensual or involved trauma,
  • whether it occurred while the person was under the influence of drink or drugs,
  • whether it occurred within a casual encounter or within a primary relationship,
  • psychological factors such as depression or fatalism in the person at risk,
  • and of course the knowledge that PEP exists.

References

  1. Henderson DK and Gerberding JL Prophylactic zidovudine after occupational exposure to the human immunodeficiency virus: an interim analysis. J Infect Dis. 160(2):321-7, 1989
  2. Cardo DM et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med 337: 1485-1490, 1997
  3. Baggaley RF et al. HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention. Int J Epidemiol 39(4): 1048-1063, 2010
  4. Baggaley RF Risk of HIV-1 transmission for parenteral exposure and blood transfusion: a systematic review and meta-analysis. AIDS 20(6): 805-812, 2006
  5. Powers KA et al. Rethinking the heterosexual infectivity of HIV-1: a systematic review and meta-analysis. Lancet Infect Dis 8(9): 553-563, 2008
  6. Boily MC et al. Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infect Dis 9(2): 118-129, 2009
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