2008 48^TH Annual ICAAC/IDSA 46^TH Annual Meeting
Washngton D.C, USA
October 25-28, 2008

Phenotype-based HIV resistance testing provides valuable information to help guide the selection of treatment regimens, particularly in patients with likely resistance to one or more ARVs. The virco^®TYPE HIV-1 report assesses the activity of ARVs against patients' virus and places the results in the context of lower and upper clinical cut-offs (CCOs) corresponding to 20% (CCO1) and 80% (CCO2) loss of response in comparison to the response expected from a fully susceptible virus in a combination ARV regimen. Recently at the combined 2008 ICAAC/IDSA meeting Lee Bacheler and colleagues from Virco presented data addressing an important aspect of interpreting those resistance test results; namely, how resistant is resistant? In other words, how rapidly do response rates decline as resistance increases between CCO1 and CCO2?

This retrospective analysis extended the linear regression modeling on clinical data previously used to define CCOs to identify the FC values associated with 50% loss of activity. In Virco's genotypic database, records for each ARV were subgrouped according to baseline activity levels of 100%-80% of wild type activity (FC<CCO1), 80-50%, 50-20% and below 20% (FC>CCO2). An analysis was performed to determine, for each drug, the proportion of samples within each of these subgroups among 93,500 samples recently submitted to Virco for routine clinical testing. The results indicated a prevalence of at least partially resistant strains (FC>CCO1) ranging from 2.6% for DRV/r and 9.2% for TPV/r to between 36% and 42% for NFV, ABC, DDI and 3TC. Among these partially resistant strains, 80-50% activity was retained for 10.6% (3TC) to 76.3% ( DRV/r) of samples.

Another important result was found in an analysis of treatment response for subgroups of samples with various levels of resistance above CCO1. For strains remaining between 80% and 50% susceptible to a given agent, response rates of 60% to >80% of the response rates observed for "fully susceptible" strains were seen. These results illustrate the potential, in the context of an optimized HAART regimen, for meaningful rates of response even when partial resistance to at least one of the drugs in the regimen is predicted.

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The authors concluded that virologic response to HAART regimens is lost gradually as baseline resistance to individual drugs increases. They also concluded that substantial antiviral drug activity can be expected against many isolates with FC in the "reduced response" category between the virco^®TYPE HIV-1 CCOs, especially against isolates with FC values close to the lower clinical cut-off.

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