Translational Medicine in HIV-1 Infection: Preclinical and Clinical Development of the Natural Anti-HIV-1 Agent, the Green Tea Catechin, Epigallocatechin Gallate, as an HIV-1 Antiretroviral Therapy

Human immunodeficiency virus-1 (HIV-1) infection ultimately results in impaired specific immune function subsequent to the initial binding of the HIV-1-gp120 to the CD4 receptor. HIV-1 eludes the immune system and leads to the onset of acquired immunodeficiency syndrome (AIDS). Ever since the discovery of the virus as the causative agent, there has been an intense effort to develop therapeutic methods to inhibit or prevent infection. The current impact of the global AIDS epidemic is staggering with over 35 million people infected with HIV. Antiretroviral (ARV) therapy has decreased the number of AIDS cases dramatically. However, ARV cannot eradicate HIV-1 completely. Along with this, the toxicity of current available anti-HIV drugs makes it difficult to maintain patients' adherence to ARV therapy. The inevitable emergence of drug-resistant mutants, especially multi-drug resistant mutants, in response to ARV therapies is problematic. The rates of success of ARV are predicated to decrease gradually with the increase in the emergence of drug-resistant strains. Therefore, continuous development of novel and natural anti-HIV agents is paramount.

The green tea catechin, epigallocathecin gallate, EGCG, with its anti-viral effects has been identified by our laboratory as one such candidate. The translational research of this natural product from bench to bedside is presented. We present evidence that EGCG inhibits the binding of HIV-1-gp120 to CD4 and subsequently HIV-1 infectivity of CD4+ T cells over a broad spectrum of virus subtypes and strains. Thus, leading to the development and initiation of a multicenter Phase I/IIa clinical trial at Texas Children's Hospital, Baylor College of Medicine and the University of Texas in adolescents and adult HIV-1-infected individuals. The clinical trial investigates the safety, toxicity and efficacy of the drug formulation of EGCG, Polyphenon® E, developed by the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI) in conjunction with Mitsui Norin Co. as an oral therapuetic in HIV-1 infection. Thus as a potential small molecule entry inhibitor of HIV-1 infectivity, Polyphenon E, would inhibit infection by the virus and thus bypass any subsequent downstream effect such as ARV drug resistance.

A cheap, readily available, and safe treatment, such as could be provided by this complementary and alternative medicine (CAM), component of green tea, would have an enormous impact on public health.