Two African herbal medicines significantly inhibit metabolism of anti-HIV drugs

This article is more than 15 years old. Click here for more recent articles on this topic

Two herbs widely used to treat individuals with HIV in Africa have a significant interaction with anti-HIV medication, potentially leading to the poor metabolisation of antiretrovirals, according to an test-tube study published in the January 3rd edition of AIDS. Extreme caution should be taken if using herbal medicines in the treatment of HIV, stress the investigators, who also state that their study shows the importance of undertaking pharmacokinetic studies to show the potential interactions between herbal medication and antiretrovirals.

The South African government has accredited 27 facilities to provide nutritional and micronutrients supplements and complementary and traditional medicines to HIV-positive patients to slow the progression of HIV disease.

Many anti-HIV drugs, including protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolised using the CYP3A4 pathway. Herbal medicines have been shown to affect levels of anti-HIV because of their impact on CYP3A4 and, in the case of protease inhibitors, P-glycoprotein as well. Some herbal medications are also known to interact with nuclear receptors such as the pregnane X receptor (PXR), which modulates expression of CYP3A and P-glycoprotein.

Glossary

glycoprotein

A protein molecule with one or more branches of sugar molecules attached to it. Many cellular and viral proteins are glycoproteins, including the outer coat proteins of HIV. A number after the gp (e.g., gp160, gp120, gp41) is the molecular weight of the glycoprotein.

drug interaction

When a person is taking more than one drug, and drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

interaction

When a person is taking more than one drug, and drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

receptor

In cell biology, a structure on the surface of a cell (or inside a cell) that selectively receives and binds to a specific substance. There are many receptors. CD4 T cells are called that way because they have a protein called CD4 on their surface. Before entering (infecting) a CD4 T cell (that will become a “host” cell), HIV binds to the CD4 receptor and its coreceptor. 

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

In a laboratory study investigators examined the effects of Hypoxis hemerocallidea (African potato) and Sutherlandia, two herbs widely used against HIV in Africa, on the metabolisation of antiretroviral drugs.

Capsules, tablets and teas of both herbs were extracted and tested for their ability to inhibit CYP3A4. The affect of the herbs on PXR and P-glycoprotein were also assessed.

African potato showed a significant inhibition of CYP3A4 activity (34% - 85% inhibition in water extraction and 31% - 79% inhibition in ethanol). Sutherlandia also inhibited CYP3A4 (55% - 69% in water extraction, 68% - 96% in ethanol).

In addition, African potato (p <0.05) and Sutherlandia (p <0.01) resulted in significant activation of PXR.

“Our findings have identified the potentially for clinically significant drug interactions for both Hypoxis hermerocallidea and Sutherlandia showing in-vitro inhibition of CYP3A4 and P-glycoprotein expression”, write the investigators.

The investigators add that their findings “suggest that 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”, conclude the investigators, “highlight the extreme caution that should be taken in introducing herbal drugs into 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 interaction potential of herbal drugs with antiretroviral drugs.” Failure to undertake such studies could, caution the investigators result in drug interactions, treatment failure, resistant HIV, and drug toxicities.

References

Mills E et al. Impact of African herbal medicines on antiretroviral metabolism. AIDS 19: 95 – 97, 2005.