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HAART vacation 2 months 0-242,000 v.l.; will 489 CD4s prevent mutations
Feb 14, 2006

On 11-17-05 I began a Dr.-supervised HAART vacation with since 1997, 400-1000 CD4s and nondetectable v.load. At 1-19-06 labs I had 489 CD4s and 242,026 v. load. Is this a "normal" rebound, or worse than usual? Back on usual triple cocktail (Viread, Ziagen, Lexiva). Will the sustained CD4s keep this v. load from creating "mutations". Never had v. load above 22,000 since diagnosies 11-95. Thanks; tried to find a similar question already asked; didn't see one.

Response from Dr. Sherer

There is no evidence that a higher CD4 cell count will protect against the development of resistance. The best way to prevent new resistance mutations is to take each ART dose as prescribed, i.e. to have as near to 100% perfect adherence as possible. Resistance can occur any time there is viremia in the presence of ART.

In general, viral rebound following drug holidays has tended to reflect the viral set point that was present prior to starting ART, so its interesting and somewhat unusual that your viral load rebounded to 10x its highest level. I note that you started HAART early in its history (1995); it may be possible that your highest viral load prior to HAART was not measured.

So far, the strongest predictors of a shorter duration of drug interruption of this type (and a more rapid CD4 decline and more rapid viral load increase) are the lowest CD4 cell count that you have ever had (the nadir) and the highest viral load. The more advanced the HIV disease, the more rapid the decline in CD4 cell count and the higher the viral rebound after drug discontinuation.

Two recent studies at the Retrovirus Conference have shed some more light on treatment interruptions. In both the SMART study and the Trivacan study in Africa, ART was stopped after the CD4 cell count was above 350, and resumed once the CD4 cell count fell below 250 cells/ml. Both studies showed strong evidence that this was not a wise strategy, and both showed more than a two fold increase in the risk of developing HIV disease progression in people who followed this strategy, compared to those who stayed on ART for the entire time. There are other studies with higher CD4 thresholds at which to resume treatment that have not been negative, so the final answer on the overall strategy is still not in, but it appears that a lower threshold of 250 CD4 cells before the resumption of ART is too low. Many clinicians are leaning towards continuing ART in all patients on the strength of this data, though that would be too all-encompassing an interpretation of these (and other) data, in my opinion.

In your case, I suggest that you repeat the viral load and CD4 cell count promptly to observe the response to your former regimen. In most patients following treatment interruptions, the response has been positive and similar to the past response; the important exception, however, is that some patients who start and stop drugs have developed some drug resistance during the process. This also is tending to make physicians less enthusiastic about drug interruption strategies...but the final answer is not in.

I urge you to talk to your doctor about these issues.


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