There have been no formal studies of the effectiveness of PEP for non–occupational exposure to HIV, and so its effectiveness in these circumstances remains unproven. However, its use is expanding in many countries.

Due to the lack of information on efficacy concerning the application of PEP after sexual exposure, the UK Chief Medical Officers' Expert Advisory Group on AIDS (EAGA) does not recommend in favour of, or against its use in such settings.  

A study in San Francisco has investigated the safety and acceptability of PEP after possible sexual or IDU exposure to HIV. Individuals who have experienced this type of exposure within the previous 72 hours are offered one month's treatment with AZT and 3TC in the form of one tablet twice a day (also known by the trade name Combivir). Other drugs (ddI and d4T) are being offered in cases where it is believed that a risk may exist of exposure to AZT and/or 3TC-resistant virus (Kahn).

The study collected data on the number of cases, the types of risk exposure, the uptake of PEP, side effects, adherence, the development of drug–resistant HIV strains, and subsequent risk behaviour. The study is not large enough to provide statistically significant evidence of PEP's effectiveness, although it is collecting data on the number of seroconversions.

In total 401 requests for PEP were received between December 1997 and March 1999. 91% of participants were men and the median age was 32 years.

375 of the 401 participants sought PEP because of sexual exposure and only 2% reported sharing of IDU equipment. Receptive anal intercourse was reported in 40% of the exposures.

PEP was supplied within 72 hours of exposure.

Certainty of source partner's HIV-positive status was expressed by 174 (43%) of participants. For the majority of participants exposed during sexual activity, the sexual exposure that prompted enrolment represented a lapse in safe sex practices rather than habitual high-risk behaviour.

In total 309 (48%) of participants completed four weeks of treatment. Complete adherence to medication in the four days before the clinic visit was reported by 84% to 78% of participants, despite high levels of self-reported side-effects, including; nausea (52%), fatigue (44%), headache (24%) and diarrhoea (15%).

This study is one of the first to provide data on the actual practice of providing PEP after sexual and IDU exposure. It demonstrated that people with sexual exposures will seek PEP. For the majority of individuals, the episode represented a lapse in safer sexual practices. The study demonstrated the feasibility of identifying persons with a sexual exposure to HIV as well as that exposed persons can be reliably and safely treated with a four-week course.

Completion rates were high at 78%. This was most likely due to several factors including, the provision of one-to-one medication adherence counselling, dispensing only a limited supply of medications at each visit which required individuals to make regular contact with staff and finally, the majority of participant took a dual nucleoside analogue regimen which was dose twice daily. Such a regimen is associated with fewer side-effects and greater ease of use than triple combinations including a protease inhibitor.

The study was not designed to evaluate efficacy, though no individuals were observed to develop antibodies to HIV at six months after exposure. 

Because persons seeking PEP are highly motivated to avoid infection, they may be in a window period in which education and counselling will have significant influence.      

Another pilot feasibility study is underway at six vaccine research recruitment sites in the USA. Men reporting high-risk exposure are randomly assigned to receive very rapid access to PEP or information about PEP and referral to clinicians who will prescribe PEP. The study will assess willingness to enrol and receive PEP, the number of PEP courses sought and received in each study arm, adherence, side effects and subsequent risk behaviour.

In New York, seven patients were enrolled via a 24-hour telephone helpline to receive an individualised antiretroviral regimen. An NNRTI was given alongside AZT and 3TC, and those patients presenting between 48 and 72 hours after exposure were given nelfinavir. One patient discontinued nelfinavir due to elevated lipid levels, otherwise side-effects were limited to GI disturbances and did not require treatment modification or discontinuation. The researchers found that with adequate counselling and support, participants were able to demonstrate excellent adherence (Torres). This was the first non-occupational post-exposure prophylaxis (PEP) pilot program in New York City and aimed to enrol 120 participants over the first twelve months.

Several other preliminary studies have reported poor rates of adherence and follow-up; for example, only three out of eight sexually exposed patients completed a PEP course at the Chelsea and Westminster Hospital in London (Easterbrook), and only one out of eight returned for all follow-up visits. At St Vincent's Hospital in New York, none of the six individuals who received PEP after sexual assault returned for HIV testing when the course was completed (Opio). It is worth remembering that numbers in these studies are low.