Being Alive; November 1992
Mark Katz, MD and reported by Jim Stoecker

The current generation of antivirals (AZT, ddI, ddC and now d4T) are only able to work in acutely infected cells. They block the reverse transcriptase enzyme that allows the virus to copy itself into DNA. These antivirals work, somewhat imperfectly perhaps, to prevent an acutely infected cell from becoming chronically infected.

Once HIV has moved beyond the reverse transcription step of its life cycle, however, it is too late for the current generation of antivirals to work. This may explain in part why these drugs are not the total solution to controlling HIV. Antivirals that work once the DNA copy is inserted in the nucleus of the T-cell, however, would work over time and thus be effective over a much greater span of the HIV life cycle.

All this is not to say that AZT, ddC, ddI are not helpful. Once a chronically infected cell releases new virus and this virus goes to find new cells to infect, these antivirals should block HIV at this point. To fight HIV, however, we also need to attack the virus as it makes new virus. Antivirals with the ability to work in chronically infected cells would significantly broaden our ability to control HIV replication.

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