HIV/AIDS: Interactions between Natural Health Products and Antiretroviral Drugs: Pharmacokinetic and Pharmacodynamic Effects
Abstract
Concurrent use of natural health products (NHPs) with antiretroviral drugs (ARVs) is widespread among human immunodeficiency virus-infected patients. This article reviews the clinical pharmacokinetic and pharmacodynamic interactions between NHPs and ARVs. Many NHPs are complex mixtures and are likely to contain organic compounds that may induce and/or inhibit drug metabolizing enzymes and drug transporters. Although the weight of evidence for the effects of certain NHPs varies and many studies of these products lack scientific rigor, it has been observed that St. John's wort clearly induces cytochrome P450 3A4 and P-glycoprotein and reduces protease inhibitor and nonnucleoside reverse-transcriptase inhibitor concentrations, thereby increasing the likelihood of therapeutic failure. Limited clinical research suggests that intake of garlic and vitamin C results in reductions in ARV concentrations. The intake of milk thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in vitro and may increase ARV concentrations, but by clinically unimportant amounts. Intake of fish oil reduces ARV-induced hypertriglyceridemia without significantly affecting lopinavir concentrations. Before recommending the use of NHPs as adjuncts to ARV use, studies should first exclude significant pharmacokinetic interactions and ensure that ARV efficacy is maintained.
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Allium poisoning symptoms may appear after one day or several days of its ingestion based on the amounts taken.
“Allium poisoning symptoms may appear after one day or several days of its ingestion based on the amounts taken [129].”
From Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review (2020) · cites this paper as [129]
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“However, challenges to collaboration include lack scientific evidence on efficacy, safety and quality of herbal medicines (Liu, Manheimer, & Yang, 2005 ), limited data on pharmacokinetic and pharmacodynamic interactions between herbal medicines and ART and their clinical significance (Lee, Andrade, & Flexner, 2006 ),…”
BackgroundAllicin in Digestive System Cancer: From Biological Effects to Clinical Treatment
Yang, Z., Li, X., Luo, W., Zhu, J., Zhao, J., Wang, M., Sang, L.-X., Chang, B., & Wang, B. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.903259 · Cited by 57 · see citing works
Herb-drug Interactions Involving Drug Metabolizing Enzymes and Transporters
Liu, C., Yi, X., Si, D., Xiao, X., He, X., & Li, Y.-Z. (2011) · Current Drug Metabolism · doi:10.2174/138920011797470083 · Cited by 55 · see citing works
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“In addition, almost no pharmacokinetic interaction studies so far have been conducted with HIV-infected patients[11].”
BackgroundGross, R., Ritz, J., Hughes, M., Salata, R., Mugyenyi, P., Hogg, E., Wieclaw, L., Godfrey, C., Wallis, C., Mellors, J., et al. (2019) · The Lancet Digital Health · doi:10.1016/s2589-7500(19)30006-8 · Cited by 36 · see citing works
Dietary supplement interactions with antiretrovirals: a systematic review
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“Thus, with their frequent coadministration, there is potential for harmful or beneficial pharmacokinetic and pharmacodynamic interactions with these agents.(2) Ginseng is an herb that is widely used in traditional Chinese and Oriental medicines for various indications.”
BackgroundSelf-citationHIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury
Neuman, M. G., Schneider, M. M., Nanau, R. M., & Parry, C. D. H. (2012) · International Journal of Hepatology · doi:10.1155/2012/760706 · Cited by 45 · see citing works
“Moreover, there is a potential for interaction with nutritional supplements [4].”
BackgroundPotential of Pharmacokinetic Profiling for Detecting Herbal Interactions with Drugs
Butterweck, V., & Derendorf, H. (2008) · Clinical Pharmacokinetics · doi:10.2165/00003088-200847060-00003 · Cited by 44 · see citing works
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Antiviral Activity of Phytochemicals: A Current Perspective
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“This reduces protease inhibitor and non nucleoside reverse-transcriptase inhibitor concentrations, thereby increasing the likelihood of therapeutic failure (77).”
BackgroundHerb-Drug Interaction betweenEchinacea purpureaand Darunavir-Ritonavir in HIV-Infected Patients
Moltó, J., Valle, M., Miranda, C., Cedeño, S., Negredo, E., Barbanoj, M. J., & Clotet, B. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01082-10 · Cited by 38 · see citing works
“Herbal medicines are often perceived to be innocuous and healthier than manufactured medicines even though they can act on the metabolism of antiretroviral agents, decreasing or increasing drug concentrations through induction or inhibition of metabolic pathways (11, 13).”
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“CAM therapies are also of questionable safety and efficacy [69].”
BackgroundHerb-Drug Interaction between Echinacea purpurea and Etravirine in HIV-Infected Patients
Moltó, J., Valle, M., Miranda, C., Cedeño, S., Negredo, E., & Clotet, B. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01205-12 · Cited by 28 · see citing works
“Nonetheless, such botanical supplements may influence the activity of various enzymes and transporters involved in the absorption, distribution, and metabolism of antiretroviral drugs, putting patients at risk of potential herb-drug interactions (11, 14).”
BackgroundBerginc, K., Trdan, T., Trontelj, J., & Kristl, A. (2010) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.730 · Cited by 28 · see citing works
“To address the gastrointestinal toxicity that occurred in the case of HIV-infected patient starting Rito therapy concomitantly with garlic consumption [7], Rito permeability changes which could arise in the presence of AGE were monitored.”
BackgroundInfluentialEffect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients
Moltó, J., Valle, M., Miranda, C., Cedeño, S., Negredo, E., & Clotet, B. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00025-12 · Cited by 28 · see citing works
“Additionally, numerous in vitro studies have shown that other botanical supplements are also capable of modulating CYP and P-gp activity and, thus, interact with drugs (3, 22, 25), although results from human in vivo studies have been less convincing (14, 15, 22, 25).”
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Berginc, K., Trontelj, J., & Kristl, A. (2010) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.25.307 · Cited by 25 · see citing works
Lee, L., Pham, P. A., & Flexner, C. W. (2012) · Annals of the Academy of Medicine Singapore · doi:10.47102/annals-acadmedsg.v41n12p559 · Cited by 24 · see citing works
Self-citationAnxiety Symptoms in HIV-Infected Individuals
Kemppainen, J. K., MacKain, S. J., & Reyes, D. M. (2013) · Journal of the Association of Nurses in AIDS Care · doi:10.1016/j.jana.2012.08.011 · Cited by 23 · see citing works
HERB-DRUG INTERACTIONS AND PATIENT COUNSELING
Ismail, M. Y. M. (2009) · Cited by 22 · see citing works
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The role of dietary supplements in cytochrome P450-mediated druginteractions
Foti, R., & Wahlstrom, J. L. (2008) · Boletin Latinoamericano y del Caribe de plantas Medicinales y Aromaticas · Cited by 21 · see citing works
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Toxic lopinavir concentrations in an HIV-1 infected patient taking herbal medications
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The effect of garlic supplements and phytochemicals on the ADMET properties of drugs
Berginc, K., & Kristl, A. (2012) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2012.659662 · Cited by 16 · see citing works
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Uso de plantas com finalidade medicinal por pessoas vivendo com HIV/ AIDS em terapia antirretroviral
de Almeida, F. M., Alves, M. T. S. S. D. B. E., & do Amaral, F. M. M. (2012) · Saúde e Sociedade · doi:10.1590/s0104-12902012000200015 · Cited by 13 · see citing works
Theranostics meets traditional Chinese medicine: rational prediction of drug–herb interactions
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“…metabolismo sistémico mediado por la CYP3A4, parece ser que también el efecto de este producto podría estar asociado a una modificación en el metabolismo presisté-mico (mediado por la CYP3A4 extrahepática) y/o en la actividad de la Gp-P (interacciones relacionadas con la biodisponibilidad) 103 .”
Bioactive Compounds and Biological Activities of Allium sativum L.
Abbasi, A., Sanej, K. D., Moradi, S., Bazzaz, S., Esmaeili, A., Ghafourian, K., Sabahi, S., Lahouty, M., Akrami, S., Aslani, R., et al. (2023) · Reference series in phytochemistry · doi:10.1007/978-3-031-29006-0_11-1 · Cited by 12 · see citing works
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Assessing Aids Research in Africa: Twenty-Five Years Later
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Herb‐drug interaction between Echinacea purpurea and darunavir/ritonavir in HIV‐infected patients
Moltó, J., Valle, M., Miranda, C., Cedeño, S., Negredo, E., Barbanoj, M. J., & Clotet, B. (2010) · Journal of the International AIDS Society · doi:10.1186/1758-2652-13-s4-p187 · Cited by 12 · see citing works
Budzinski, J. W., Foster, B. C., Trudeau, V. L., Drouin, C. E., Bafi-Yeboa, N., & Arnason, J. T. (2008) · Pharmaceutical Biology · doi:10.1080/13880200701729844 · Cited by 11 · see citing works
“…if selected (Table 1) commercially available teas and capsule preparations of several popular herbal NHPs used by the HIV+ community (CATIE, 2005; Lee et al., 2006), related phytochemicals, and a few HIV drugs could inhibit CYP3A4-mediated metabolism of a reference substrate and stimulate P-gp…”
BackgroundTherapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects
Chauhan, A. P. S., Dewali, S., Pathak, V. M., Bisht, S. S., Chauhan, R., Kaur, D., Tuli, H. S., Haque, S., & Ahmad, F. (2025) · Discover Oncology · doi:10.1007/s12672-025-02591-3 · Cited by 11 · see citing works
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Primary Care Issues for HIV-Infected Patients
Cohen, D. E., & Mayer, K. H. (2007) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2007.01.001 · Cited by 9 · see citing works
Interactions Between Natural Health Products and Antiretroviral Drugs
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Influencia de la medicina alternativa en el tratamiento antirretroviral de gran actividad
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Clinical management of drug interaction with antiretroviral agents
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Evidence‐Based Clinical Assessment of Herbal Formulations: Traditional and Modern Insights
Banerjee, D., Banerjee, S., Shah, P., Singh, A., & Saharan, V. A. (2025) · doi:10.1002/9781119769484.ch25 · Cited by 7 · see citing works
Herb and Modern Drug Interactions
Mehmood, Z., Khan, M. S., Qais, F. A., Samreen, S., & Ahmad, I. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-814619-4.00019-7 · Cited by 6 · see citing works
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“31 % of ingested dose (Lee et al., 2006).”
MethodInfluentialMngomezulu, K., Madlala, P., Nkabinde, S. A., Nkabinde, M., Ngcobo, M., & Gqaleni, N. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1618187 · Cited by 5 · see citing works
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Interaction of Traditional Remedies Against HIV, Nutrients and ARVs
Barros, E. (2011) · InTech eBooks · doi:10.5772/19621 · Cited by 4 · see citing works
“…mixtures containing organic compounds many of which can induce and/or inhibit the enzymatic pathways involved in the metabolism of ARV drugs (Lee et al., 2006). www.intechopen.com Recent Translational Research in HIV/AIDS 120 St. John’s wort, a well known natural health product, is commonly…”
BackgroundMethodInfluentialClinical Relevance of Drug Interactions in HIV-Infected Patients Receiving Antiretroviral Therapy
Amariles, P., Giraldo, N. A., & Jose, M. (2011) · InTech eBooks · doi:10.5772/19408 · Cited by 4 · see citing works
“(Lee et al., 2006)”
Tagne, A. M., Nya, P. C. B., Tsapi, A. T., Essoh, A. K. E., Pembouong, G., Michael Alliance Ngouadjeu Ngnintedem, Marino, F., & Cosentino, M. (2019) · AIDS and Behavior · doi:10.1007/s10461-018-02388-2 · Cited by 4 · see citing works
Pharmacology of antiretroviral drugs
Merry, C., & Flexner, C. W. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4557-0695-2.00013-4 · Cited by 4 · see citing works
Self-citationDrug Interactions with Garlic and Ginger Supplements
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Behavior, antioxidant, and metabolomics effects of Allium tuncelianum
Abbak, N., Nemutlu, E., Reçber, T., Gül, A. Ş. D., Akkoyun, H. T., Akkoyun, M. B., Yılmaz, G., Ekin, S., Bakır, A., & Arıhan, O. (2024) · Food Science & Nutrition · doi:10.1002/fsn3.4022 · Cited by 3 · see citing works
“The toxicity of Allium depends on the amount and frequency of consumption, and it has been shown to cause Heinz body formation in the erythrocytes in many animals (Lee et al., 2006; Salgado et al., 2011).”
BackgroundPires, C. M. B. F., & Silva, I. C. (2021) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2021.100477 · Cited by 3 · see citing works
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Effects of Natural Products on Sugar Metabolism and Digestive Enzymes
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Study of natural product adverse events in adult HIV‐infected patients in Canada
Sparks, E., Zorzela, L., Necyk, C., Hughes, C. A., & Vohra, S. (2021) · HIV Medicine · doi:10.1111/hiv.13155 · Cited by 2 · see citing works
“Polypharmacy, such as the mixing of NHPs with prescription medications, increases the risk of a potential drug– NHP interaction or AE [8,14].”
BackgroundPharmacology of Antiretroviral Drugs
Merry, C., & Flexner, C. W. (2008) · Elsevier eBooks · doi:10.1016/b978-1-4160-2882-6.50020-4 · Cited by 2 · see citing works
Self-citationBioactive Compounds and Biological Activities of Allium sativum L.
Abbasi, A., Sanej, K. D., Moradi, S., Bazzaz, S., Esmaeili, A., Ghafourian, K., Sabahi, S., Lahouty, M., Akrami, S., Aslani, R., et al. (2024) · Reference series in phytochemistry · doi:10.1007/978-3-031-44746-4_11 · Cited by 2 · see citing works
Drug Interactions with St. John's Wort
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PHYTOCHEMICAL ANALYSIS OF Turnera diffusa WILLD
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Medicina alternativa y sida: hacia una comunicación más eficaz sobre las plantas medicinales
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Natural Health Product Utilization in Warfarinized Children; Prevalence and Knowledge
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HIV-1 Treatment-Experienced Patients: Treatment Options and Management
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Farmacocinética poblacional de Lopinavir y Ritonavir en pacientes adultos infectados por el VIH
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Clinical Pharmacokinetic Interactions between Herbal Supplements and Anticancer Drugs
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“According to recent epidemiological reports, ~40% of Americans use CAM “natural products” including herbal medicines, botanicals, and other dietary supplements during their lifetime [10-14].”
BackgroundGenetic-Based Biomarkers in Psychiatry: An Integrative Approach
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Drug interactions in HIV and AIDS
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Self-citationAntiretroviral Therapy that Includes, Protease Inhibitors - Induced Hepatotoxicity: A Review
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“Moreover, there is a potential for interaction with nutritional supplements.(39) Physicians should also be aware that patients with chronic viral hepatitis coinfection have additional impairment of CYP3A activity in the presence of ritonavir, compared to HIV patients without viral hepatitis, even at the low doses of 1…”
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“These herbal substances could induce enzymes involved in the metabolism of antiretroviral drugs resulting in low plasma concentrations of the drugs or alternatively inhibit the enzymes resulting to higher plasma concentrations of the drugs which would exacerbate their toxicity (Lee et al., 2006).”
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Herb–nutrient–drug interactions
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- Authors
- Lee, L. S., Andrade, A. S. A., & Flexner, C.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Flexner, Charles
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-10-15
- Volume
- 43
- Issue
- 8
- Pages
- 1052-1059
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W2111738803
- Cited by
- 102
- References
- 78
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 6 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 2 · 2013: 8 · 2012: 14
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Complementary and Alternative Medicine
- National Center for Complementary and Integrative Health (F05-AT 02031, F05AT002031)
- Topics
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- natural health products, antiretroviral drugs, drug interactions, HIV/AIDS, pharmacokinetic interactions, pharmacodynamic interactions, Hypericum perforatum, CYP3A4, P-glycoprotein, protease inhibitors, non-nucleoside reverse transcriptase inhibitors, garlic, vitamin C, Silybum marianum, Echinacea, goldenseal, fish oil, lopinavir, drug-metabolizing enzymes, drug transporters
- MeSH terms
- Biological Availability, Cytochrome P-450 Enzyme System, Humans, Plant Extracts, Plants, Medicinal, Glucuronosyltransferase, ATP Binding Cassette Transporter, Subfamily B, Member 1, Herb-Drug Interactions, Anti-Retroviral Agents, Cytochrome P-450 CYP3A
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