How soon should PEP be used?

When used, PEP should be initiated promptly. Animal research suggests that PEP may be ineffective if started later than 24 to 36 hours after exposure. The animal study upon which these estimates are based comes from macaque monkeys given tenofovir as the sole PEP drug.¹

In this study, 24 macaque monkeys were divided into six groups of four. They were all given a dose of simian immunodeficiency virus (SIV – the equivalent to HIV in monkeys) ten times larger than the dose which would be expected to infect 50% of monkeys – a dose that should have infected all of them. They were then treated with tenofovir starting at various times after infection and continued for various time periods. The results were as follows:

A: Control group (treated only with saline, not tenofovir: 100% infected: all seroconverted by week four.

B: Tenofovir started 24 hours after exposure and continued for 28 days: probably none infected (one monkey eventually showed antibodies to SIV after 32 weeks but free or cell-associated virus was not detected in any monkey).

C: Tenofovir started 48 hours after exposure, continued for 28 days: all seroconverted to SIV by week 16, though virus was only detectable in 50% of monkeys.

D: Tenofovir started 72 hours after exposure, continued for 28 days: all seroconverted by eight weeks, though virus only detectable in 50%.

E: Tenofovir started 24 hours after exposure, continued for 10 days: 50% eventually seroconverted, though virus only detectable in one (25%).

F: Tenofovir started 24 hours after exposure, continued for three days: all seroconverted by eight weeks, virus detectable in 50%.

It is this study that is the basis for the recommendation that PEP should be started within 24 hours of exposure, though it may be 50% effective up to 72 hours after exposure.

A discussion of PEP for non-occupational risks recommends against initiating treatment more than 72 hours after the exposure,² 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.”

A 2006 UK survey by the Health Protection Agency³ of PEP provision at ten London HIV clinics found differences in the time starting PEP, between healthcare workers and those exposed sexually or through injecting drug use. For people seeking PEP after non-occupational exposure, the average time elapsed between exposure and taking PEP was 23 hours, whereas for occupational exposure it was two hours.