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Drug Resistance Question
Feb 23, 2002

Dear Dr Gallant, if somebody is on a triple combo and begin to develop resistance to one of the drugs, how much time does he has for a switch in order not to have more resistance developing? Currently, the routine for viral load and CD4 count done here is on a 6 months cycle and there is no way that we could change that here as there are only a handful of hospitals serving a largely infected population. Assuming that resistance develop in between the 6 months interval, will I have a chance to react before serious damage is done? Appreciate if you could shed some light on this issue. Thanks

Response from Dr. Little

In general, I perform viral load testing every 3 months for exactly this reason. There are data to suggest that once a patient develops virological failure (ie a detectable viral load) after being completely suppressed - it is better to switch earlier rather than later after the relapse in viremia is detected. The risk incurred by continuing treatment in the face of a detectable viral load - in terms of developing further drug resistance - depends on the drugs in use. For drugs like 3TC and the NNRTI (efavirenz, nevirapine), if a patient develops detectable virus and does not yet have resistance to these drugs (and is taking one or both of them) - then the risk of developing resistance is quite high if a change in therapy is not made within weeks. However, even for the drugs that require multiple point mutations to generate significant drug resistance, 6 months is more than enough time to develope significant additional drug resistance if not acted upon. So yes - bottom line, I really think that viral load testing needs to be more frequent and followed up rapidly by virologic confirmation if a detectable viral load is detected and resistance testing performed while the viral load is still relatively low to permit the most rapid optimization of therapy possible to avoid further selection of drug resistance.


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