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resistance testing
Oct 30, 2006

I have been HIV infected since the late 1980s. Three years ago, I cycled off the meds in a highly controlled NIH study. After three months a resistance test was performed. No surprises here resistant to many of the nukes I used mono-therapy in the early 1990s. I remained off the meds for two years. Based on the first resistance test, three drugs were selected and I began taking these meds. Six months after re-starting the meds, another resistance test was run. The results were astounding: not only did the resistance to the nukes magically disappear but the three drugs that I am taking are indicating resistance although the viral response is adequate. Any thoughts?

Response from Dr. Wohl

In general, resistance to HIV meds does not go away. These resistant viruses are archived in cells where under the right conditions they can re-emerge. Resistance tests are best at detecting the most common strains of HIV circulating in the blood. If you are no longer on the meds that the virus is resistant to, these viruses fade to the background and teh test can miss them. Re-apply the meds and the resistant strains pop up as they can better survive in the face of these meds while other drug sensitive strains do not.

It is all about survival of the fittess a la Darwinian evolution. Non-drug resistant virus is the most fit and outgrows resistant virus EXCEPT when HIV meds are taken, surpressing the non-resistant virus but leaving the resistant ones standing.

This also explains why on a combo that your virus may have resistance to your viral load is lower than when you are off meds (it is clearly not undetectable as resistance testing can not be done when there is little virus around to test). Resistant virus is mutated. It is often less fit and thus less able to work effectively to replicate and pick off T-cells.

Stay on meds you are resistant to and the funky mutant virus is selected for rather than the bad-ass regular virus that evolved over the past who-know-how-many-years to be the best it can be at ruining your T-cell's day. A down side of staying on meds your virus is resistant to is the development of additional resistance mutations that can compromise subsequent HIV therapy.

So, it can be that the resistance test is being less than perfect and that the resistance you had is still there. But, on the other hand, resistance may be keeping your virus off guard and less able to hurt you. When possible, a better approach for long term supressionis to use drugs your virus is sensitive to.

DW



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