What this means in practice
Do not combine St John's Wort with a protease-inhibitor or NNRTI-based regimen. If low mood is the reason it is being considered, that is a conversation with the HIV team, who can pick an antidepressant that does not induce CYP3A4.
What people say
A natural antidepressant with none of the side effects of the prescription ones, which makes it an appealing option for someone managing low mood alongside a demanding daily drug regimen.
What the evidence supports
In healthy volunteers, St John's Wort cut indinavir exposure by a mean of 57% and cut the 8-hour trough concentration by 81%; the authors state a reduction of that size could lead to drug resistance and treatment failure (Piscitelli 2000). Reduced plasma levels of antiretrovirals including indinavir and nevirapine are listed among the well-documented St John's Wort interactions (Borrelli 2009), and HIV protease inhibitors appear on the UK regulator's list of affected medicines (Henderson 2002). No study has measured viral load or resistance on the combination, so the clinical consequence is inferred from the size of the drop rather than observed.
How it is supposed to work
Protease inhibitors and non-nucleoside reverse transcriptase inhibitors are cleared by CYP3A4, which hyperforin switches on. Blood levels fall, and what matters most is the trough, the lowest level between doses, because that is where the virus gets room to replicate and to select for resistance.
Which way it runs
One-directional. St John's Wort lowers antiretroviral levels. The measured human study is on the protease inhibitor indinavir; nevirapine, a non-nucleoside reverse transcriptase inhibitor, is named by the review literature rather than measured in a study read directly here. Nucleoside reverse transcriptase inhibitors and integrase inhibitors are cleared differently and are not covered.
What is still missing
The herb's appeal here is that it costs nothing in side effects, and the price it actually charges is not a side effect at all: it is the quiet loss of four fifths of the drug level that was holding the virus down, with resistance the thing that gets built in the gap.
Sources
- Indinavir concentrations and St John's wortPiscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J, 2000
- Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observationsBorrelli F, Izzo AA, 2009
- St John's wort (Hypericum perforatum): drug interactions and clinical outcomesHenderson L, Yue QY, Bergquist C, Gerden B, Arlett P, 2002