Previous studies suggested that the molecular mechanism of action for both classes of BA derivatives were quite unique in comparison with currently known anti-HIV-1 drugs that target HIV-1 reverse transcriptase or protease. Although both classes of BA derivatives shared the same betulinic acid core, they exhibit very different modes of anti-HIV-1 action. Two classes of chemically modified BA derivatives are reported to inhibit HIV-1 replication at nanomolar concentrations, such as PA-457 (class I) and IC9564 (class II). BA and its derivatives have demonstrated high anti-HIV-1 activity and cytotoxicity against a variety of tumor cell lines comparable to some clinically used drugs. BA possesses a wide spectrum of biological and pharmacological activities, such as antimalarial and anti-inflammatory activities. Common structural features of the lupane skeleton are its five-membered ring and isopropylidene and it is found predominantly in bushes and trees forming the principal extractive of the bark of birch trees. BA is particularly promising because it is well characterized and can be purified in relatively large amounts. Betulinic alcohol (BA) is a pentacyclic triterpene alcohol with a lupane skeleton. Of these, terpenes, isolated from medicinal plants, have gained much interest due to their significant anti-HIV-1 activities along with their structural diversity. Natural products, of which structural diversity is so broad, are convenient sources for the effective discovery of anti-HIV-1 agents with expected lack of cell toxicity. The fact that their use will be controlled by women obviously constitutes a very significant advantage. Unlike condoms, they will not create a physical barrier to intimate contact, nor will they necessarily be contraceptive. Microbicides may theoretically target the incoming virus at several steps of molecular events driving viral entry and/or viral replication. Therefore, new methods of prevention that can be controlled by women them-self, such as microbicide formulations, are becoming urgently needed.

Interventions aimed to provide significant changes in sexual behaviour and increased frequency of barrier methods (male and female condoms) use have not proven their efficacy to decrease the HIV-1 epidemic in developing countries. Sexual transmission of HIV-1 is predominant worldwide, and male-to-female transmission during heterosexueal intercourse is the major way of HIV-1 acquisition in exposed women, especially in developing countries.

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