Toward Resistance

Toward Resistance

If the virus were not so variable, one or two AIDS drugs would suffice. But the virus changes its genome with practically every copy. The reason for such flexibility is that RT lacks a proofreading mechanism and does not repair copy errors. Mutations in the HIV genome can result in changes in the composition of its proteins. Most of these changes are detrimental or even lethal to the virus, but with many millions to even billions of virus copies produced daily in the same patient, chances are high that a viral variant will arise quickly whose target protein remains functional even in the presence of a drug. Such a virus is resistant to the drug.

Suppressing viral replication means reducing the number of experiments the virus can perform to produce a resistant variant. In order to increase the barrier of the virus to escape toward resistance, several drugs targeting different viral proteins are given simultaneously. This scheme, called highly active antiretroviral therapy, or HAART, renders therapies effective for much longer periods of time. The virus always wins. Most current therapies remain effective for only months to a few years.