Use of African Herbal Medicines May Result in Bidirectional Drug Interactions and Put Patients at Risk of Treatment Failure, Viral Resistance or Drug Toxicity

In response to the AIDS crisis in Africa, the South African National Department of Health has recently accredited 27 facilities, whose mandate to provide AIDS care includes the provision of “interventions that delayed the progression of the disease, including nutritional and micronutrient supplementations, and providing traditional and complementary  medicines.”

Many antiretroviral medications, such as HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors are predominantly metabolized through the CYP3A4 oxidative metabolic pathway, and in the case of HIV protease inhibitors are also substrates for drug transporters such as P-glycoprotein.

Herbal medications have been shown to affect the serum levels of antiretroviral medication through their effects on CYP3A4 metabolism and P-glycoprotein. In addition, some herbal medications are also known to interact with nuclear receptors such as the pregnane X receptor (PXR), which modulates the expression of CYP3A4, and P-glycoprotein.

Canadian researchers analyzed the effect of two herbs in common medical use for HIV in Africa, HYPOXIS HEMEROCALLIDEA (African potato) and SUTHERLANDIA, for their potential to cause drug interactions with common antiretroviral agent metabolizing mechanisms in vitro.

The findings have identified the potential for clinically significant drug interactions for both H. HEMEROCALLIDEA and SUTHERLANDIA showing in-vitro inhibition of CYP3A4 and P-glycoprotein expression.

Further in-vitro studies demonstrated the propensity for activation of PXR, a nuclear receptor that controls the activation of both P-glycoprotein and CYP3A4.

The combination of these findings suggest that the co-administration of these drugs with antiretroviral agents may result in the early inhibition of drug metabolism and transport followed by the induction of decreased drug exposure with more prolonged therapy.

These results highlight the extreme caution that should be taken in introducing herbal drugs into the routine care of HIV patients in any setting including the developing world, and underscore the need for appropriately designed pharmacokinetic studies to unveil the true drug interaction potential of herbal drugs with antiretroviral agents.

The authors conclude, “Failure to do this may result in bidirectional drug interactions, which may put patients at risk of treatment failure, viral resistance or drug toxicity.”

“Given the Global Fund's recent announcement of funds to make antiretroviral therapy widely available in Africa, and the South African Ministry of Health, along with member states' and non-governmental organizations' endorsement of traditional African herbs such as HYPOXIS and SUTHERLANDIA as HIV/AIDS remedies, policy makers and the research community should make investigations into the clinical ramifications of the use of these herbs on antiretroviral therapy an urgent priority.”

01/14/05

Reference
E Mills and others. Impact of African herbal medicines on antiretroviral metabolism. AIDS 19(1): 95-97. January 3, 2005.