Chemotherapy of human immunodeficiency virus (HIV) infection: anti-HIV agents targeted at early stages in the virus replicative cycle

Several compounds have been identified that inhibit an early stage in the replicative cycle of the human immunodeficiency virus (HIV): i) virus adsorption: polysulfates, polysulfonates, polycarboxylates, polyphosphates, and polyoxometalates; or ii) virus-cell fusion: plant lectins, negatively charged albumins and betulinic acid derivatives; iii) virus fusion/uncoating: bicyclam derivatives; iv) reverse transcription: dideoxynucleoside analogues, acyclic nucleoside phosphonates and non-nucleoside reverse transcriptase inhibitors. In principle, HIV may develop resistance to any of these specific anti-HIV agents. However, virus breakthrough can be completely prevented if these agents, alone or in combination, are added to the HIV-infected cells from the beginning at sufficiently high (‘knock-out’) concentrations.