Present Status and Future Prospects for HIV Therapies

Johnston, Margaret I.; Hoth, Daniel F.

doi:10.1126/science.7684163

Cited by 185 publications

(105 citation statements)

References 213 publications

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“…Numerous other RT inhibitors have been described (1), and some of them are in clinical trials. Although these drugs strongly inhibit viral replication in vitro, the long-term benefits of these drugs on clinical progression of disease are uncertain (2). After prolonged therapy, drug-resistant viruses emerge because of point mutations in the polymerase gene that give rise to amino acid changes in RT (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Animal model for the therapy of acquired immunodeficiency syndrome with reverse transcriptase inhibitors.

Überla

Stahl–Hennig∥

Böttiger

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

121

116

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The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) is the major target for antiretroviral therapy of the acquired immunodeficiency syndrome (AIDS). While some inhibitors exhibit activity against most retroviral RTs, others are specific for the HIV-1 enzyme.To develop an animal model for the therapy of the HIV-1 infection with RT inhibitors, the RT of the simian immunodeficiency virus (SIV) was replaced by the RT of HIV-1.

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mentioning

confidence: 99%

Animal model for the therapy of acquired immunodeficiency syndrome with reverse transcriptase inhibitors.

Überla

Stahl–Hennig∥

Böttiger

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

121

116

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“…Long-term suppression chemotherapy appears to improve the survival of patients with AIDS, but it is difficult to use for long-term chemotherapy. 6) Its major drug-related toxicity is bone marrow suppression, which limits the dose of AZT that can be used.…”

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confidence: 99%

Polysaccharide fromAspalathus lineariswith Strong Anti-HIV Activity

Nakano

Itoh

Mizuno

et al. 1997

Bioscience, Biotechnology, and Biochemistry

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Polysaccharide that had been extracted with 1% sodium carbonate from Rooibos leaves (Aspalathus linearis) showed strong anti-HIV activity. Du-Zhong leaves also showed anti-mY activity, although lower than the extract of Aspalathus linearis, but Japanese tea leaves and a hot water extract of Aspalathus linearis did not. The anti-HIV activity of the alkaline extract from Aspalathus linearis was recovered mainly in the 25-75(i"o ethanol-precipitated fraction. The polysaccharide almost completely inhibited the binding of HIV-1 to It is inferred from these results that the polysaccharide from Aspalathus linearis is involved in the m~:chanism for virus binding to T cells. Key words: anti-HIV activity; polysaccharides; in vitro; alkaline extract; Aspalathus linearisIt is vitally important to find an effective chemotherapy for the acquired immunodefficiency syndrome (AIDS), Many researchers have been prompted to search for selective antihuman immunodefficiency virus (HIV) agents. Increasing numbers of these anti-viral agents are presently in various stages of development and testing, and some of them have recently been licensed for use by humans. 1 ,2) 3'-Azido-3'-deoxythymidine (azidothymidine, AZT) and 2'J'-dideoxyinosine have improved the clinical and immunological status of patients with AIDS and AIDS-related complex.3 .4) The target of AZT is viral reverse transcriptase,5) and the phosphorylated products of AZT would be held responsible for bone marrow suppression. Long-term suppression chemotherapy appears to improve the survival of patients with AIDS, but it is difficult to use for long-term chemotherapy. 6) Its major drug-related toxicity is bone marrow suppression, which limits the dose of AZT that can be used. )There are many substances from plant extracts that have so far shown anti~HIV activity in vitro, including lignin and lignified materials,8.9) tannin and related substances,10) and plant lectins. 11 ) Unfortunately, these substances showed relatively high cytotoxic activity.Rooibos tea, a kind of herb tea, which is made of leaves and sprigs of Aspalathus linearis, is popular in Republic of South Africa, Europe, and Japan. This plant only grow in Sedarberg mountain, West Cape. 12.13) Rooibos tea contains a small amount of tannin but no caffeine. The hot-water extract (tea) contains many volatile constituents such as phenolic compounds,14) many kinds of flavonoids and shows broad pharmacological effects.1 5-17) We report here that the alkaline extracts from Aspalathus linearis strongly suppress the HIV-induced cytopathic effect with HIV-l (HTLV-IIIB) infected MT-4 cells in vitro, the cytotoxicity being extremely low, and that the substance responsible would be an acid polysaccharide mainly composed of glucose and uronic acid. Materials and Methods Materials. Rooibos tea leaves (Aspalathus linearis) and Du-Zhong leaves(Eucommia ulmoides Oliv.) were obtained from A.Le. Co. (Nagoya, Japan) and Nikki Kogyo Co. (Hiroshima, Ja-ran), respectively.Preparation of the alkaline extract. Unless otherwise indicated, ...

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“…Specificity of expression has already been envisaged using either specific promoters 159 -161 that can direct expression of the transgene in specific cells or inducible promoters, such as those containing a Tat activating region element, whose expression is induced by the HIV Tat protein. 162,163 Long-term expression of the transgene has to be addressed through the analysis of factors involved in the decrease of transgene expression, 164 -166 such as the hypermethylation of DNA, 167,168 or interferences between cotransferred promoters. 169 New vector designs have already resulted from these studies but remain to be fully tested with primary hematopoietic cells.…”

Section: Discussionmentioning

confidence: 99%