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Report of a WHO Consultation on Traditional Medicine and AIDS: Clinical Evaluation of Traditional Medicines and Natural Products (Geneva, 26-28 September 1990)
(1990; 20 pages) View the PDF document
Table of Contents
View the document1. Introduction
View the document2. Background information
View the document3. Preclinical considerations
View the document4. Clinical considerations
View the document5. Recommendations
View the documentAnnex 1. List of participants
View the documentAnnex 2. Guidelines for clinical trials with traditional medicine products used in the treatment of AIDS and AIDS-related diseases
View the documentAnnex 3. Proposed who clinical staging system for HIV infection and disease1
 

2. Background information

2.1 Traditional medicine products used in HIV infection and disease

Several countries have traditional medicine products that are used in the treatment of HIV infection and to ameliorate symptoms and prolong the life of persons with AIDS.

In vitro anti-HIV activity has been reported for the following Chinese medicinal plants: Glycyrrhiza uralensis, Hypericum perforatum, Viola yedoensis, Altemanthera philoxeroides, Andrographis paniculata, Arctium lappa, Lithospermum erythrorhizon, Coptis chinensis, Epimedium grandiflorum, Lonicera japonica and Prunella vulgaris.

The protein trichosanthin (compound Q or GLQ 223), isolated from the Chinese herb Trichosanthes kirilowii, has been used not only in China as an abortifacient, but also to treat patients with AIDS in unofficial trials in the United States of America. Compound Q has also been approved for limited clinical trial by the United States Food and Drug Administration. It has been reported to interfere with the replication of HIV, and selectively to eliminate infected cells.

Kampo is a pharmacotherapeutic branch of Oriental medicine that originated in ancient China and is still being used today in Japan. Originally Kampo medicines consisted of a variety of crude drugs prepared in several hundred different combinations as decoctions, powders or pills. Today, however, the extracts of crude drugs are formulated under strict quality control using state-of-the-art technology. Kampo medicines play a large role in modern medical care in Japan and are expected to continue to do so in future.

One Kampo medicine, Sho-saiko-to, has been used to treat a number of different diseases, including viral hepatitis. It has been reported that Sho-saiko-to (which contains glycyrrhizin) has an immunoenhancing effect on the interleukin cascade. Thus, Sho-saiko-to might have potential for use in the treatment of some phases of HIV infection. This medicine also has anti-inflammatory activity and induces the production of lipocortin, a protein produced by the cell nucleus. This is only one example of a Kampo medicine with pharmacological activities that could be useful in the treatment of persons with AIDS.

2.2 Summary of immunological aspects and considerations

WHO has proposed that the following prognostic categories of the disease should be used in describing the course of HIV infection and disease: (1) asymptomatic/persistent generalized lymphadenopathy; (2) early (mild) disease; (3) intermediate (moderate) disease; and (4) late (severe) disease (AIDS) (see Annex 3). After becoming infected with human immunodeficiency virus type 1 (HIV-1), persons may remain asymptomatic for years before the onset of AIDS. During this asymptomatic phase there may be functional abnormalities of both T-cells and B-cells, even if lymphocyte numbers remain normal. At present, it is not clear whether the immune system abnormalities in either the asymptomatic phase or clinical AIDS are due solely to the direct effects of HIV-1 or whether they also reflect defects existing prior to infection in the host immunoregulatory mechanisms.

One characteristic feature of retrovirus infections is the ability of the virus to insert a DNA copy of its viral RNA genome into the genome of the host cell. During HIV infection, the integrated proviral genome may remain in an inactive state until appropriate activating signals stimulate viral expression. Because of the possibility of induction of HIV expression by T-cell activating factors, such as mitogens and antigens, it is recommended that in clinical trials with traditional medicines with a known immunomodulating effect, antivirals should also be given. On the other hand, the development of humoral and cell-mediated responses against HIV soon after acquisition of infection with HIV clearly demonstrates the ability of the immune system to counteract HIV-1 infection. Immunostimulators might, therefore, also be considered for clinical testing, either alone or together with a specific antiretroviral agent for the treatment of patients in stages of the disease with a small virus burden, e.g., in the asymptomatic phase.1

1 Report of a WHO informal consultation in preclinical and clinical aspects of the use of immunomodulators in HIV infection, Geneva, 3-5 April 1989, AIDS, 4(12): WHO1-WHO14.

Drugs active against HIV enzymes (e.g., reverse transcriptase inhibitors) may also benefit patients with AIDS. However, screening for anti-HIV activity using single-cell immune cultures may be of only limited value, because the pathogenesis of AIDS involves several types of immune cells and complex relations among the cytokines of the immunological network.

Animal models will play a central role in AIDS research in the coming years. Important models include HIV-infected chimpanzees, immunodeficiency virus-infected simian monkeys, and ungulates and cats with HIV-related lentivirus infections. However, animal models may not exhibit all the features of human HIV infection.

2.3 Current drug-screening activities

Medicinal plants that have been used as anti-infective agents in the prevailing systems of traditional medicine in different geographical areas are being systematically collected in order to evaluate their anti-HIV potential. For this purpose a collaborative project has been established between the WHO Collaborating Centre for Traditional Medicine at the University of Illinois, Chicago, USA, and the WHO Collaborating Centre for AIDS at the National Bacteriological Laboratory in Stockholm, Sweden. The preparation of primary extracts is being coordinated by the Chicago group, and the extracts are then sent to the Stockholm facility for anti-HIV testing in vitro. The two centres have so far evaluated 36 extracts representing 18 plant species. Activity has been found in extracts from two species, which are of great interest because of their low toxicity.

The finding of two active species in 18 samples represents a high rate of success. If the initial project goal of collecting 200 samples by the end of 1990 is attained, a projected total of about 11-12 active plant species can be expected to serve as candidates for bioassay-directed fractionation and eventual isolation of active principles. It is WHO’s policy to ensure that the benefits from the development of drugs as a result of collaborative efforts such as this one are, as far as possible, made widely available on an equitable basis.

In addition, bimonthly and annual reports to WHO on anti-HIV active compounds of known structure and natural product extracts having anti-HIV and related activities (e.g., reverse transcriptase inhibition, other enzyme inhibitions, etc.) are provided through a computerized data base, NAPRALERT (Natural Products Alert), established by the WHO Collaborating Centre in Chicago.

The plant-derived chemicals of known structure listed in Table 1 are those reported to date to have anti-HIV activity.

Table 1. Phytochemicals that inhibit HIV in vitroa

Compound

Compound class

Arabinitol, L: 1,4-dideoxy-1,4-imino:

Carbohydrate

Castanospermine

Indolizidine

Castanospermine, 6-0-Butyryl:

Indolizidine

Colchicine

Alkaloid

Fucitol, L: N-(5-carboxylmethyl-l-pentyl)-1-5-amino:

Carbohydrate

Glycycoumarin

Coumarin

Glycyrrhizin

Triterpene

Glycyrrisoflavone

Flavonoid

Gossypol

Sesquiterpene

Gossypol, (+):

Sesquiterpene

Gossypol, (-):

Sesquiterpene

Hypericin

Quinoid

Hypericin, pseudo:

Quinoid

Licochalcone A

Flavonoid

Licoflavonol, Iso:

Flavonoid

Licopyranocoumarin

Coumarin

Nojirimycin, 1-deoxy:

Carbohydrate

Oenothein B

Tannin

Papaverine

Isoquinoline

Viola yedoensis polysaccharide

Polysaccharide

Prunellin

Polysaccharide

Punicalin

Tannin

Quinic acid, 1,3,4,5-tetra-O-galloyl:

Tannin

Quinic acid, 3,4,5-tri-O-galloyl:

Tannin

Quinic acid, 3,4-di-O-galloyl-5-O-galloyl:

Tannin

Quinic acid, 3,5-di-O-galloyl-4-O-galloyl:

Tannin

Quinic acid, 3-O-digalloyl-4,5-di-O-galloyl:

Tannin

Ricin A Chain

Peptide

Soybean saponin B-1

Triterpene

Soybean saponin B-2

Triterpene

Sulfapatrinoside I

Triterpene

Sulfapatrinoside II

Triterpene

Trichosanthin, alpha: (GLQ223)

Protein

a Excludes sulfated polysaccharides.

 

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