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Replcation capacity
Aug 24, 2004

What exactly is meant by replication capacity and how can this be tested? Has this become an important part of HIV care??? Can you explain. I have been infected with HIV for 15 years and this is the first I heard of this.

Response from Dr. Sherer

We have long known that drug resistance mutations sometimes can impair the ability of the virus to replicate, and hence lead to a reduced 'replication capacity'. With the advent of phenotypic testing, in which the patient's virus is tested in the presence of single ART drugs in a single cycle assay, clinicians gained the ability to measure the replication capacity of a virus in comparison to wild type virus in addition to the susceptibility (or lack of it) to various drugs.

There are many reasons to be careful not to assign more value to a single replication capacity than is due. What we are really interested in is viral fitness, i.e. the ability of the virus to replicate and spread from cell to cell in real people. Viral fitness may be influenced by a variety of factors, including the host immune response, state of disease (early or advanced), entry protein tropism (CCR5 or CXCR4), current and past ART, and other factors we are unaware of.

So whether a single cycle 'replication capacity' as currently measured actually bears a direct relationship to viral fitness is unknown. I advise you not to worry about it, and ask your doctor if there is any reason in your case to seek such information. More often than not, there is not.

In general, virus containing NRTI resistance mutations have been observed to have reduced replication capacity, e.g. with 3TC resistance and the M184V. Also in general, virus with NNRTI resistance mutations do not appear to have reduced replication capacity. And with PI mutations, the picture is mixed, depending on the specific mutations.

Finally, replication capacity has been offered as one possible explanation for the observation that ART provides a survival benefit even in patients with full resistance to a given regimen (when compared to similar patients in whom all ART is stopped).

So an important lesson from the concept of replication capacity is that resistance is a relative, not absolute, phenomenon. Resistance can be overcome with higher drug levels in some instances (e.g. PI resistance), for example.

While all resistance is undesirable, and every effort should be made to prevent it, some resistance may have an effect that is of some benefit to patients...i.e., a reduced replication capacity, IF that is found to indeed be associated with lower viral fitness, and IF that results in virologic or immunologic benefits for patients.

Whether the replication capacity now qualifies as 'an important part of HIV care' is unknown.


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