Interactions of Tropical Pacific Medicinal Plants with HIV and Anti-Retroviral Drugs

Papua New Guinea (PNG) has a long tradition of medicinal plant use, employing both endemic and regional plants. PNG also has an established HIV epidemic and has instituted programs to provide anti-retroviral therapy (ART) to people living with HIV (PLH). The antagonistic or augmentative effects of herbal preparations on ART are of great concern when trying to optimize treatments for PLH. We report here an on-going, integrated study of extracts and extract fractions from more than 50 of the most commonly used PNG medicinal plants for: 1) cytotoxicity to T leukemia cells (332/1142 toxic at 50 µg/ml), 2) the ability to induce HIV in latently HIV-1 infected primary T memory cells, and in a confirmatory J-LAT T leukemia cell line (25/1542 potently active in both), 3) the ability to inhibit HIV killing of infected T leukemia cells (52/1142 active), 4) the ability to inhibit ART drug metabolizing enzymes CYP1A2 (58/132 positive), CYP3A4 (48/132 positive) and CYP2D6 (64/132 positive), and 5) the ability to induce expression of CYP1A2 and CYP3A4 (8/70 and 19/70 positive, respectively; 5 positive for both). Specific plants are identified with potent activity in selected assays, providing unequivocal rationale for caution and counseling regarding their use in combination with ART. Work supported by JTA International Sponsor Award No. 10020310 and NIH U01 TW006671.