PEP Efficacy: Background and Evidence
There are currently no data from randomised controlled trials that provide evidence of the efficacy of PEP in preventing HIV acquisition. Animal data have been particularly informative regarding the importance of starting PEP as early as possible following an exposure event, the 72-hour post-exposure window period for starting PEP and the 28-day duration of the course.6-10
Further evidence for the use of PEP has also been extrapolated from data from mother-to-child transmission11-13 and following occupational exposures in health care workers,14 where a retrospective case control study demonstrated that PEP users had an 81% reduction in HIV seroconversions compared to those who did not take PEP.15
The only clinical effectiveness study of PEP in humans was performed among 200 Brazilian high-risk HIV-negative men who have sex with men (MSM). Seroincidence in the cohort was very similar to that expected in the population. There was no difference in PEP efficacy, likely due to a lack of statistical power. However, HIV seroconversions were only 1/68 in the PEP group compared with 10/132 in the group not receiving PEP.16
Although PEP is likely to be highly effective when initiated in a timely manner and taken as prescribed, there have been documented HIV seroconversions following PEP after both sexual and occupational exposures. In Australian17 and international18,19 observational studies, seroconversions subsequent to a PEP course following sexual exposures, although rare, were most commonly associated with ongoing risk behaviours. Other reasons for seroconversion have included delays in PEP initiation,18,20 poor adherence to PEP20,21 and already established HIV infection at the time of PEP initiation.22
The rare cases of PEP failure following occupational exposures were mostly reported over two decades ago.15,23-25 Occupational PEP failures have been described due to resistance mutations in the virus of the source26 and possible early primary HIV infection in an Australian healthcare worker who seroconverted after sustaining a needlestick injury from a viraemic, treatment-experienced source, despite commencing PEP only two hours later.27 Notably, despite completing the 28-day course, the healthcare worker had stopped PEP for four days in the third week.
Completion of the 28-day PEP course has historically been low, ranging from 48% to 88%.28 However, less tolerable older PEP regimens, particularly those containing zidovudine,29,30 have been replaced by better-tolerated regimens in recent years, including the use of tenofovir disoproxil fumarate (TDF) as one component of the PEP backbone with an integrase inhibitor (versus a protease inhibitor) as a third drug, where required.29,31,32
Education on the importance of PEP adherence and seeking timely clinical review for PEP regimen modification if side-effects impact adherence remains a cornerstone of PEP management, along with appropriate post-PEP testing.
There is no evidence for greater efficacy of two or three-drug PEP regimens. (See Appendix B) Recommendations in international and national guidelines are based on transmission risk assessment, epidemiology (including co-factors), local prescribing practices and cost.
Acknowledgement of Country