Bay Area Reporter - June 29, 2001
Matt Sharp, Survive AIDS Writers Pool

The answer may be just that - a heavily mutated virus, or even partially resistant virus may be a weaker virus, unable to reproduce as much as once suspected. Although the goal is to stop virus replication completely, there are those people that simply do not have that option, that have become resistant to every drug. If current research is confirmed, a weaker, less fit virus may just keep heavily treated folks healthy.

It is not completely understood how people can stay healthy with a mangled, mutated virus, though there is mounting evidence showing people who have been on triple regimens who have detectable virus levels are able to maintain relatively stable T-cell levels and good clinical health. Dr. Steven Deeks from San Francisco General Hospital has been following a cohort of heavily treated patients for several years and gathering important information about a population of people otherwise infrequently studied. One of Deeks's studies in a recent New England Journal of Medicine article showed that despite the presence of drug resistance, HIV drugs may provide a benefit in terms of stable T-cells, viral load, and further resistance. In other words, anti-HIV drugs may still be useful even in those who are have been on multi-drug therapy and are resistant.

Earlier this year, Deeks presented another important study at the retrovirus conference in Chicago. In this study, with sophisticated viral fitness assays, Deeks showed that those patients who were resistant to protease inhibitors had a less fit virus than those who were susceptible.

With more studies we may find what has kept me surviving with a detectable viral load for over five years may partially be a weaker virus.

These studies lead to the belief that resistant, replication-incompetent virus is weaker, or less fit; the virus is not doing the damage once thought. But if this is the case, how can physicians and patients tell how weak the virus is, even if it may not be resistant to antivirals? How can this news be translated to produce a clinical benefit?

Deeks's work has inspired Virologic, a diagnostic company in South San Francisco, to develop tests to understand and correlate reproduction capacity, or viral fitness. The company, now just under six years old, has grown as the demand for resistance testing has increased. Virologic has licensed the technology to look at the phenotype of HIV. Rather than looking at the individual resistant genes and mapping like the genotype test, (another resistance test) Virologic's PhenoSense phenotype assay actually can determine which individual drugs will stop HIV replication in the laboratory. PhenoSense is an expensive test now covered by Medicaid in 13 states including California and New York. Other third-party payers are joining the bandwagon as physicians are seeing the value of the test in constructing regimens that will work for patients.

Interestingly, the PhenoSense test led to the discovery of the new replication capacity or fitness assay by the company. A complicated process, the new test is a modification of the PhenoSense that uses a chemical which, in simple terms, produces light in the presence of HIV replication. The company discovered that in using this chemical a brighter light correlated to a fitter virus. Through modification of the PhenoSense the new test will eventually be standardized to show how able a virus is to reproduce. Nick Hellman, vice president of clinical research at Virologic, told me that the new assay is being patented and will need to go through more research for validation. But he seemed to think it would be more widely available in about a year.

Looking back, I realize that according to the understood pathogenesis of HIV, I should have been dead long ago. All of us were led to believe as cocktail therapy became the rage, that an undetectable virus was needed to keep HIV in check. That over the years as the drugs failed, so did immune systems, and then people died. But it may now be that the drugs we have are useful enough despite resistance, along with some immune response.

The news of resistant virus being less fit is good news for the thousands of people who are long-term survivors. And with few new drugs coming to the market this news is welcome as older drugs can be utilized to prolong and save lives despite a high viral load. Further work needs to be done however to validate this encouraging breakthrough in order to provide the utmost care in long term HIV patient management.
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Always watch for outdated information. This article first appeared in 2001. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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