Evidence for three-drug versus two-drug PEP regimens
PEP regimens may consist of two or three antiretroviral drugs. 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 or combination of drug classes have historically achieved better treatment outcomes for HIV. In previous years, three-drug combinations were recommended for the treatment of HIV. However, more recently, dual HIV therapy including an integrase strand transfer inhibitor (INSTI), or non-nucleoside reverse transcriptase inhibitor (NNRTI) has shown non-inferiority to previously recommended three-drug regimens.116,117
A systematic review and meta-analysis of animal PEP studies found no difference in efficacy between single nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) or INSTI PEP, dual NRTI PEP or triple NRTI and protease inhibitor (PI) PEP, although several of the included studies were not powered to detect a difference.7
For neonatal PEP, a large randomised controlled trail found similar reductions in intrapartum HIV transmission for two drugs (zidovudine + nevirapine) and three drugs (zidovudine, lamivudine and nelfinavir), although both multi-drug regimens further reduced intrapartum HIV transmission by 50% over zidovudine given alone.9
There are only two published studies on tenofovir alafenamide used in combination with cobicistat and elvitegravir, both of which reported good tolerability, adherence, and completion rates.118,119 However, we do not generally recommend elvitegravir for PEP due to its requirement of pharmacokinetic boosting by cobicistat and its higher likelihood of drug-drug interactions than other INSTIs.54
Where a third drug is recommended, either dolutegravir or raltegravir can be used. Comparison of their characteristics is shown in Table 3.