For two-drug PEP, the following is not generally recommended:

• zidovudine. Co-formulated tenofovir disoproxil and emtricitabine is better tolerated.²⁵

For three-drug PEP regimens, the following are not generally recommended:

• boosted regimens containing ritonavir or cobicistat
  • due to the potential for drug-drug interactions with multiple prescription and over-the-counter medications (refer to Liverpool HIV Drug Interactions checker website)
• boosted protease inhibitors such as ritonavir and lopinavir
  • associated with more adverse events
  • associated with lower adherence compared with raltegravir as a third PEP drug⁵⁵
• co-formulated tenofovir alafenamide, emtricitabine, cobicistat and elvitegravir (Genvoya®)
  • one tablet daily, reported to be well tolerated for PEP with high completion rates ^59-61
  • not generally recommended due to drug interactions with cobicistat, and cost (see Drug-Drug Interactions and Appendix C).
• efavirenz
  • Poorly tolerated due to neuropsychiatric side-effects²⁴
• rilpivirine
  • shown to be well tolerated, with high adherence and completion rates for three-drug PEP in combination with tenofovir disoproxil and emtricitabine^62,63
  • combination three-drug single tablet (Eviplera®) now discontinued
  • not generally recommended for PEP due to the necessity to take with a meal
  • the potential interactions with other prescribed and over-the-counter medications (most notably antacids for gastric reflux which constitute over 10% of all over-the-counter medications dispensed in Australia).⁶⁴