• 
• 

Three Part Question

In [adults sexually exposed to HIV] how [efficacious is postexposure prophylaxis] at [reducing risk of seroconversion]?

Clinical Scenario

A 24 year old female attends the emergency department at 10pm on a Sunday night with her boyfriend. She tells you that a condom broke during penile-vaginal intercourse, and her boyfriend is HIV positive, though she is not. She had recently read a newspaper article about postexposure prophylaxis and wished for it to be precribed. You wonder if it would reduce the risk of seroconversion in this patient.

Search Strategy

Medline, 1966-06/06, Cinahl 1982 06/2005, Embase 1980- 06/2006, using the OVID interface
[acquired immune deficiency syndrome/pc or OR HIV infection/pc] AND [anti-HIV agents/tu OR PEP.mp. OR PEPSE.mp. OR NONOPEP.mp. OR NPEP. OR nonoccupational exposure.mp.] AND [anti-HIV agents/tu] AND [exp unsafe sex] AND exp vagina/vi]

Search Outcome

1 relevant paper was found.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Otten RA Smith DK Adams DR Pullium JK Jackson E Kim CN Jaffe H Janssen R Butera S Folks TM October 2000 USA	16 naive female pig-tailed macaques aged 3 - 5 years weighing 5.5 - 8.5 kg, inoculated vaginally with at least 100 times the pig-tailed macaque infectious dose of HIV-2 before being commenced (at 12, 36 or 72 hours post-exposure) on a 28-day postexposure prophylaxis regime of tenofovir or a placebo.	Animal study.	The presence (or otherwise) of systemic HIV-2 infection (defined as detection of HIV-2 provirus in PBMC or ILN cells and/or virion-associated HIV-2 RNA 24 weeks post-inoculation).	None of the four macaques who received PEP 12 hours after exposure developed systemic infection. None of the four macaques who received PEP 36 hours after exposure developed systemic infection. One of the three macaques (initially four, one unanticipated fatality) who received PEP developed systemic illness.	Animal study,thus result may not be directly applicable to humans. No blinding of investigators.

Comment(s)

All of the previous work on PEP has been done using intravenous inoculae or percutaneous exposure in animals, and is thus perhaps more akin to needlestick exposure. The paper cited above is novel in that it recreates a much more common means of exposure, and is thus more appplicable to administration of PEP following sexual exposure. It also confirms the intuitive insight that the earlier PEP is administered after exposure, the more effective it is. While it is an animal study, it is the best evidence available at this time, and since an equivalent study in humans is ethically controversial and practically very difficult due to the the large cohort required, it is likely to remain so. There have been no studies thusfar examining the efficacy of PEP given outwith 72 hours post-exposure, though it is likely that it would have some benefit: there exists a window of opportunity, which may be as long as 14 days, after exposure before systemic dissemination of the virus occurs.

Clinical Bottom Line

PEP should be administered as soon as possible after the exposure, ideally within 72 hours.

References

1. Otten RA Smith DK Adams DR Pullium JK Jackson E Kim CN Jaffe H Janssen R Butera S Folks TM Efficacy of Postexposure Prophylaxis after Intravaginal Exposure of Pig-tailed Macaques to a Human-Derived Retrovirus (Human Immunodeficiency Virus Type 2) Journal of Virology October 2000; 9771 - 9775