Background: Side effects and PEP discontinuation were suggested to be more common among individuals on post exposure prophylaxis (PEP) taking PI-regimens and this could affect compliance, resulting in a potential reduction of PEP efficacy. To evaluate short-term toxicity and discontinuation of PEP by regimen, we reviewed data collected in our National Registry.

Methods: Individuals were assigned to group A (2 NRTIs), or group B (2 NRTIs plus PI), according to their initial regimen. Discontinuation was assumed as < 28 days. Lost to follow up or data not available (57 persons), PEP discontinuation because the source tested HIV negative (n. 340), and subjects who self-withdrew without side effects (38 group A [15%]; 42 group B [10%]), were excluded. Statistical analysis was undertaken with χ² test.

Results: Until 08/01, 216 group A (92% ZDV plus 3TC), and 380 group B individuals (85% ZDV and 3TC, plus 92% IDV) were included in the analysis. 127 individuals in group A (58.8%) and 253 in group B (66.6%) experienced at least one side-effect (OR 1.40; 95% CI 0.97-2.00; p = 0.07). The proportion of PEP discontinuation because of side-effects was 21.3% in group A (46 subjects, mean PEP duration 10.7 days, median 8, range 1-27) and 27.9% in group B (106 subjects, mean 9.3, median 7, range 1-26) (OR 1.43, 95% CI 0.95-2.18; p=0.09). Of the 106 group B individuals who discontinued PEP, 18 initially only discontinued the PI (after a mean of 6.4 days, median 4.5, range 1-20), however PEP was completely discontinued because of side effects after a mean of 13.4 additional days on two NRTIs (median 11, range 1-26). Finally, 44 (12%) group B individuals discontinued the PI after a mean of 9.4 days (median 7.5, range 1-27), but completed the 4-week course of two NRTIs. Adding these 44 individuals to the discontinuations observed in group B, the difference becomes statistically significant (OR 2.41, 95% CI  1.62-3.63, p <  0.001).

Conclusions: Although PI including PEP appears associated with a higher risk of side effects and discontinuation, these findings do not justify per se the exclusion of PI from the initial regimen. Indeed, our study showed that in most individuals the full-course, 3-drug regimen can be completed. Unless already contraindicated, we suggest beginning PEP with a 3-drug regimen and discontinuing the PI in the case of side effects that are not manageable, in order to prolong and possibly complete the 4 week treatment.