Enhancing the potential benefits of HIV post-exposure prophylaxis

In this issue, Herida et al. [1] show that an untargeted HIV post-exposure prophylaxis (PEP) programme in France is not cost effective. Previous French, Canadian and American papers have suggested that PEP guidelines result in increased prescribing for low-risk exposures [2–4]. French guidelines recommend that clinicians consider ‘the perception of the risk leading a person to request prophylaxis’ when determining PEP eligibility. In contrast, a targeted PEP programme in San Francisco with clear eligibility criteria was cost effective [5,6]. Taken together, these studies suggest that PEP policies and programmes should target individuals at highest risk of HIV exposure and encourage clinicians to adhere to evidence-based prescription criteria. Cost-effectiveness studies of non-occupational PEP have evolved from modeling HIV transmission risk based on exposure type and likelihood of source HIV infection, efficacy at different adherence levels, and cost [7–10] to applying such models to real-life programmes [1,5,6]. Early studies showing that PEP was only cost-effective after the highest-risk exposure scenarios raised concerns about programmes that offered PEP after lower-risk exposure circumstances. Such concerns are borne out in the current study, in which fewer than 16% of individuals who were prescribed PEP had an exposure estimated to be cost saving or cost effective. The San Francisco study also included exposure characteristics that, in isolation, were not cost effective. However, by targeting outreach and counseling clients about the potential risks and benefits of PEP based on their exposure, most individuals who chose PEP were at high risk of HIV exposure and transmission. If a potentially infectious body fluid comes in contact with a mucous membrane (e.g. eye or oral, nasal or genital mucosa) or non-intact skin (punctured, cut or abraded), HIV transmission is possible and consideration of PEP is warranted. Anyone with such an exposure with a source who is known to be HIV infected or who is at significant risk of HIV infection should be offered PEP. The healthcare provider must help the client realistically assess the risk of acquiring HIV infection as a result of the exposure and make an informed decision about taking PEP. The higher the risk, the more directive the healthcare provider should be towards the decision to take PEP. Ultimately, if the client meets the criteria, he/she should be given the opportunity to use PEP. Clinicians should be willing not to prescribe PEP and to provide supportive counseling and referrals when PEP is not indicated. Some guidelines distinguish between recommending or offering PEP based upon the HIV status of the source [11]. Of note is the fact that the two documented seroconversions in this study among individuals without other known exposures were in persons whose exposure was with a source of unknown HIV status. Three out of seven seroconversions occurred in individuals whose source HIV status was unknown in San Francisco [12]. Important information, even about sources who were initially considered ‘anonymous’, can often be obtained by telephone, e-mail or in person and does not require actual testing. Individuals seeking PEP should be encouraged to speak with their source partner about HIV status and risk. It may be difficult for a potentially exposed individual to feel confident about a source's claim that he/she is HIV negative. To evaluate the likelihood that the source of exposure may be HIV infected, local HIV risk demographics must be considered. For PEP to be a truly effective HIV prevention tool, it must be integrated into a comprehensive prevention programme. Responding to a single sexual exposure with a biomedical intervention without addressing the risk context is a missed opportunity. Subsequent HIV risk has not increased in individuals who were offered five sessions of risk reduction counseling as part of their PEP intervention [13]. A randomized study comparing risk behavior and seroconversion in individuals randomly assigned to two or five sessions of counseling is currently under analysis. The healthcare provider must also help the client make sense of confusing messages about low per-contact transmission rates, a low risk of source HIV infection based on demographics, and prevention messages that emphasize the need always to have protected sex. The challenge is to provide reassurance and to motivate the client's concern about staying HIV negative and support efforts to reduce subsequent risk. A Russian roulette or other culturally appropriate analogy may be useful. There may be modifications to the French PEP programme that could enhance its cost effectiveness, including the use of two rather than three drugs for PEP, and the elimination of routine laboratory testing [14]. Future cost-effectiveness analyses should take into account the costs associated with adverse drug reactions, which are probably more common with three-drug based regimens [14]. In summary, French PEP guidelines resulted in the increasing use of PEP for lower-risk exposures and the programme was not cost effective. In contrast, a programme that targeted outreach to the highest-risk populations and employed clear prescribing criteria was cost effective. No cost-effectiveness analyses to date have considered the costs and potential benefits associated with the risk reduction counseling that should always accompany PEP as an HIV prevention strategy. Incorporating PEP services into HIV prevention, occupational health and sexual assault treatment programmes may increase the likelihood that outreach will be appropriately targeted and that valuable risk reduction, prevention and trauma counseling will accompany the biomedical intervention.

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