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Treatment Advances in HIV Disease and New Antiretroviral Strategies

Significant changes have taken place over the past few years in our understanding of HIV infection, our ability to monitor infected patients, and our ability to successfully treat HIV-positive patients.

I. Viral Dynamics

A. The virus and infected CD4 cells turn over very quickly. The virus replicates rapidly at all stages of illness.

1. About 1 x 1010 virions are produced daily in an infected patient.

2. The t1/2 of plasma virions is about 6 hours.

3. CD4 cells are produced and destroyed in infected persons zidovudine AZT protease inhibitors at 10-100 times the normal rate.

4. The gradual fall in CD4 count during clinical latency appears to be due to an inability of CD4 production to match mediated CD4 destruction.

5. There is no virologic latency. Replication proceeds relentlessly, and the body eventually fails to keep up.

6. The amount in the bloodstream at any given time is the result of a dynamic equilibrium between production and destruction of new particles.

B. Drug resistance mutations develop easily.

1. Replication errors are common in RNA viruses like, due to the absence of DNA proofreading mechanisms. It is estimated that one mutation occurs in every 3 newly produced genomes. Given the daily production of 1 x 1010 virions, it is likely that every possible mutation, and many combinations of mutations, exist in a given patient's population, even in the absence AIDS of