Key recommendations
- The recommended first-line two-drug regimen is co-formulated tenofovir disoproxil and emtricitabine.
- There is no evidence to support the greater efficacy of three- over two-drug regimens, although we continue to recommend three-drug regimens in certain situations based on evidence that a higher number of drugs or combination of drug classes has historically achieved better treatment outcomes for HIV.
- Where a third drug is recommended, either dolutegravir or raltegravir can be used.
- In renal impairment, dosing adjustment of drugs may be necessary (Figure 1).
- No dose adjustment is necessary for any recommended PEP drugs in hepatic impairment.
The recommended first-line two-drug regimen is co-formulated tenofovir disoproxil and emtricitabine because it is:
- now available in affordable, generic forms,
- available on private script if not dispensed from hospital or specialist clinic
- well tolerated
- one-tablet daily
- has good anogenital tissue penetration.51
There is no direct nor compelling indirect evidence to support the greater efficacy of three- over two-drug regimens; rather, it has been extrapolated from evidence that a higher number of drugs and combination of drug classes has historically achieved better treatment outcomes for HIV. A summary of the evidence for three-drug versus two-drug PEP is provided in Appendix B.
Where a third drug is recommended, either dolutegravir or raltegravir can be used. Comparison of their characteristics is shown in Table 3.
Table 3. Characteristics of dolutegravir versus raltegravir when used as the third agent for HIV PEP52
| Dolutegavir | Raltegravir | |
|---|---|---|
| Cost per 28-day course (Appendix C) | $630 | $570 |
| Pill burden | 1 X 50 mg taken once per day | 2 X 600 mg taken once per day |
| Shelf-life | 5 years | 2 years |
| Anogenital tissue penetration53 | Generally poorera | Generally bettera |
| Pregnancy category | B3 | B3 |
| Pregnancy dosage54 | 1 X 50mg taken ONCE per day | 1 X 400mg taken TWICE per day |
| Food restrictions54 | None | None |
| Crush/dissolve | Yes | Yes |
| Adverse events (AEs)27,28,55-57 | Generally mild | Generally mild |
| Prevalence of AEs27,28,55-57 | Similar | Similar |
NOTE: reported in-vivo differences in anogenital tissue penetration between drugs have not resulted in any clinically significant differences in studies of treatment as prevention, so it is assumed their efficacy would be comparable for PEP
STANDARD REGIMEN Two-drug regimen: Tenofovir disoproxil* /emtricitabine 200 mg 1 tablet orally daily Three-drug regimen: above two-drug regimen PLUS Dolutegravir 50 mg 1 tablet orally daily OR (alternative) Raltegravir 1200 mg (2 X 600 mg tablets orally daily) ALTERNATIVE REGIMEN IN RENAL IMPAIRMENT^ If eGFR < 30 mL/min: seek specialist HIV and renal advice immediately If eGFR = 30-49 mL/min: use the following dosages58 |
Tenofovir disoproxil one tablet orally every 48 hours PLUS Emtricitabine one tablet orally every 48 hours OR lamivudine 150 mg orally daily PLUS (if three-drug PEP indicated) Dolutegravir 50 mg orally daily OR raltegravir 1200 mg orally daily |
NO DOSE ADJUSTMENTS NECESSARY FOR ANY RECOMMENDED REGIMENS IN HEPATIC IMPAIRMENT58 |
* There are four salts of tenofovir disoproxil available with slightly different dosages in combination with emtricitabine which are considered bioequivalent: maleate, phosphate, fumarate and succinate
^eGFR: estimated glomerular filtration rate
eGFR is recommended to be calculated by Cockcroft Gault equation :58 Creatinine Clearance Calculator
^ alternative dosing with emtricitabine oral solution or tenofovir disoproxil granules may be used where available; for dosage guide refer to: Liverpool HIV Drug Interactions checker website.
