Profiling an Emerging 3-DCR HIV NYC Recombinant
Recombinomics Commentary
February 15, 2005
>> Bowen said the San Diego resident tested positive for the rare HIV strain last fall - after the patient's health provider sent a sample of his or her blood to ViroLogic, an HIV typing reference laboratory in Northern California.
There was no alarm until the New York City man recently became ill and was found to have a molecular strain resistant to virtually all anti-viral drugs. His case prompted public health officials nationwide to check with the reference lab for a similar strain among other HIV patients.
The reference lab's database then linked the New York strain to that of the San Diego person and an unidentified New York City resident. <<
The added detail above paint a picture of an emerging disease. The 3-DCR NYC HIV was tested in three separate, but related assays. One assay looked at drug sensitivity which has two components. One measures how well a given drug inhibits the ability of the virus to grow, and another identifies mutations in the protein targets of protease or polymerase inhibitors. For 3-DCR-NYC this test showed that the virus was resistant to all three major drug classes, and identified a series of mutations.
A second assay was Replication Capacity, which measures how well the virus grows in the absence of treatment. 3-DCR NYC was found to have a wild type RC.
The third assay determines the co-receptor. Use of the R4 receptor is associated with drug resistance, but is also usually associated with reduced RC. 3-DCR-NYC had a CXCR4 tropism.
Thus, testing of samples using all three assays showed that the same virus was able to use the R4 receptor without reduced RC. This is the combination that makes the virus unusual. More information is gained from the profile of mutations that lead to resistance for the FDA approved drugs. The San Diego patient and second NYC patient appear to have a matching virus. The isolates are being sequenced to see if there are any differences between the viruses.
The 3-DCR-NYC patient progressed rapidly. Disease progression in the other two patients has not been disclosed. However, it is clear that the new virus is emerging and is relatively rarely, although it has been detected on both coasts and in patients infected prior to the infection of the NYC patient.
Thus, the commercial assays offer a means for tracing the origins of the virus, if prior samples are available. Disease progression in many individuals will be required to determine progression times in patients infected with this emerging variant.
However, a newly emerging variant that significantly increased disease progression would give a profile similar to the reported sequence of events. A rapid progression in a naïve patient would be noticed, as would a profile that combined CXCR4 tropism with wild type RC. This combination may signal recombination.
Finding both sets of these unusual properties in the same individual(s) is cause for concern.
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