Providing PEP after sexual or IDU exposures presents different challenges than for occupational or perinatal exposures. Persons exposed to HIV from sexual or IDU activities may not accurately assess their risk for infection and may delay seeking treatment.

Identifying a person's source partner and determining his or her HIV status after sexual exposure may be problematic.

Concerns have been raised that if PEP were provided for sexual  or IDU exposure, individuals would experience unacceptable side-effects or would inadequately adhere to the treatment regimen or refuse to return for follow-up HIV testing.

Additionally, there is the concern that PEP would fail to fully suppress the virus and rapidly induce resistance to the drugs used. This risk is greatest, if people take it in the belief that they are HIV- negative when in fact they are already HIV-positive.

The point has been raised that the availability of PEP for sexual and IDU exposures might paradoxically increase risk behaviour. For this reason the San Francisco study described above included a number of sessions of risk reduction counselling.     

At a session discussing PEP during the Eleventh International Conference on AIDS in Vancouver in July 1996, physicians voiced their sense of unease at limiting PEP to health–care workers. As has been pointed out, “The probability of HIV infection due to puncture by a contaminated needle is similar to that estimated for a single episode of unprotected receptive anal or vaginal intercourse with an infected partner or for a single episode of injection–drug use with HIV–contaminated equipment” (Katz). If PEP works, then ethically it should be made available to individuals who are placed at significant risk of infection through other exposure routes.

The American Society of Law, Medicine and Ethics convened an interdisciplinary Working Group on HIV Testing, Counselling, and Prophylaxis After Sexual Assault, which published its recommendations in 1994. At that time the efficacy of PEP was less clearly established, but nevertheless the group concluded that survivors should be provided with information about the availability of PEP to enable them to decide whether or not to use it, “based on a risk assessment of the exposure. The risk assessment should consider available information on the serostatus of the assailant, the type of exposure (anal, vaginal, or oral penetration and ejaculation), the nature of the physical injuries, and the number of assaults”, as well as the potential for drug side–effects (Gostin).

Research amongst a cohort of gay men in four US cities caused researchers to conclude that the per-exposure risk of unprotected receptive anal intercourse was greater than that of a single needlestick injury, and that this level of risk justified offering PEP after such a potential sexual exposure. However, it is worth noting that this research took place between 1992 and 1994, and infectivity may have been altered by the widespread use of HAART (Vittinghof).

It will be difficult to define the boundary between cases of sexual risk which are high enough to justify offering PEP, and those in which the risk of infection is sufficiently low that the financial cost of PEP and the risk of drug side–effects is felt to be unjustifiable. For instance, the CDC guidelines indicate that combination therapy may be reasonable for health–care workers who experience mucosal exposure to semen even where there are only grounds for suspicion, rather than certainty, that the source patient is HIV–positive. How does this differ from the situation of any gay man who gets fucked without a condom in a large city in the UK?

A 1998 review of ethical and clinical implications of PEP for non-occupational exposure concluded that it would be prudent to consider local HIV prevalence rather than relying on per-exposure risks calculated for very high prevalence cities when considering the likely need for PEP (Lurie), although it should be noted that the four city study mentioned above did distinguish between the per-contact risk of receptive anal intercourse with a partner known to be HIV-positive, and one of unknown HIV status.

When used, PEP should be initiated promptly, since animal research suggests that PEP may be ineffective if started later than 24 to 36 hours after exposure. A recent discussion of PEP for non–occupational risks recommends against initiating treatment more than 72 hours after the exposure (Katz), although the CDC guidelines argue that starting even one to two weeks post–exposure may be justified in cases of the highest risk. The protocol used at San Francisco General Hospital notes that “after an exposure, most health–care workers are upset and find that decisions about treatment are very hard to make. We recommend that the exposed person start therapy. Therapy can be stopped later, after the exposed person has had a chance to talk with their clinician and loved ones. Once the immediate crisis has passed, it is usually easier to make the best decision.” (San Francisco General Hospital Epi–Center). If PEP is ever to become a practical option for non–occupational exposure, a new system of 'rapid response' clinic services may be required to provide prompt access to treatment.

According to Guidance from the DoH, PEP following occupational exposure should ideally be started within an hour of exposure. The guidelines recognise that presentation following a non-occupational (sexual or IDU) exposure is unlikely to be sufficiently prompt to derive maximum benefit from PEP. This would imply a need to distribute 'starter packs' in the community, along with education in their proper use. The obvious model for this is the way that pregnant women with HIV are given their first dose of nevirapine to take home and keep for the onset of labour, prior to hospital admission. However, for sexual transmission there would be added costs due to packs that were unused and issues concerning shelf-life and safe storage. An alternative would be to educate GPs, pharmacists, and accident and emergency staff in delivering PEP, to ensure out-of-hours access.