Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
With the advent of highly active antiretroviral therapy (HAART), the therapeutic landscape for HIV infected individuals has changed irrevocably. From what can be likened to a defensive approach to AIDS, juggling prophylactic therapies and treating opportunistic pathogens, HAART has taken us onto the offensive, restoring a sense of optimism to physicians and patients alike in the developed world. It is, however, to quote Churchill only “the end of the beginning.”
It is worth considering why current antiretrovirals are inadequate and what can be done to remedy this situation. Successful antimicrobials target processes that are unique to the pathogenic organism. In fungi, this is often membrane and cell wall synthesis. In bacteria, it is usually cell wall synthesis or the distinctive features of prokaryotic protein synthesis. In viruses, it is predominantly the enzymes. Two of these, reverse transcriptase and protease, are the therapeutic targets in HIV but the actual processes of reverse transcription and protease cleavage are brief events, certainly compared with that of cell wall synthesis in bacteria. The chance of there being subtherapeutic drug levels at critical times during viral replication is, therefore, large. There is additionally no “post-antibiotic effect.” Thus, the imperative for strict adherence to therapy in antiretroviral treatment is as great if not greater than for any other antimicrobial regimen.
The obvious response to this narrow therapeutic window is to seek other targets in the virus life cycle. The difficulty is that most of the remainder of the cycle utilises normal cellular processes and functionally important cellular proteins, interference with which might seriously damage both infected and uninfected cells.
The remaining unique feature of the virus is its nucleotide sequence and, by derivation, the amino acid sequence of its proteins. Reagents which target these specifically would leave cellular functions intact. Thus, the concept of gene …