Background International non-occupational post-exposure prophylaxis (NPEP) guidelines recommend routine use of three drug NPEP regimens, despite absence of evidence for greater prevention efficacy compared with two drug regimens. This study examines the potential for excess HIV seroconversions among high-risk men who have sex with men (MSM) reporting receptive anal intercourse with a source of unknown HIV serostatus (RAIU) following a two-drug versus a three-drug NPEP regimen.

Data for MSM in the Victorian NPEP service database between 10 August 2005 and 31 December 2012 were linked with all Victorian HIV notifications up to 31 December 2013. The primary outcome was NPEP failure following NPEP presentation among MSM reporting RAIU, stratified by the number of drugs prescribed.

Among 1482 MSM reporting 2002 episodes of RAIU and prescribed two- or three-drug NPEP, 70 seroconverted to HIV, but only 19 were considered possible NPEP failures. HIV diagnosis incidence among men reporting RAIU was 1.2/100 person years (PY) (95%CI=1.0-1.6); 1.1/100 PY (95%CI=0.8-1.4) among MSM prescribed two drugs and 2.2/100 PY (95%CI=1.4-3.7) among MSM prescribed three drugs (P<0.01). Of the 19 possible NPEP failures, 13 (0.7%) were prescribed two drugs and six (2.7%) three drugs (P<0.001).

This study suggests that two-drug NPEP regimens do not result in excess seroconversions compared with three-drug regimens when used following RAIU. Clinical services should carefully consider their use of three drug NPEP and whether resources might be better invested in other prevention strategies, particularly pre-exposure prophylaxis (PrEP).