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Message from CPCRA 007 and other combination studies

“You’re only naïve once.” More ubiquitous than even the unimaginative Steelers-Cowboys Superbowl Sunday banter was the sight of euphoric virologists high-fiving each other in the conference corridors with hearty cheers of “It’s the virus, stupid.” While the sound bite of the Third Retroviral Conference may have been “Hit it hard, and hit it early,” a goodly share of the week’s data hinted at how much more complicated this obliterate-the-virus approach may turn out to be–at least, the “hit it early” part. A closer look at combo antiretroviral studies such as the CPCRA 007 study, the indinavir+AZT+3TC study and others make an equally compelling case for remaining drug-naïve as long as possible–especially if the much ballyhooed benefit of the protease inhibitors turns out to be anything as transient as that of their RTI predecessors. (Remember BW 02?) These studies showed that combination therapy could whack quite a wallop against the virus–even in persons with advanced HIV disease, but the impact of these new drugs was most pronounced in those with limited or no prior treatment.

AZT resistant virus more virulent than wild-type?

When the Concorde study and the extended follow-up of ACTG 019 revealed that while AZT monotherapy extends the asymptomatic period of HIV infection, these same individuals expire more rapidly once developing symptomatic disease, researchers were at a loss to explain why. Now it appears that possible explanations are emerging, and they are just short of frightening. A research paper from U.S. Army AIDS researcher Douglas Mayers et al. showed that mutated HIV which has grown either phenotypically or genotypically resistant to AZT is 5-times faster to replicate. One wonders if Concorde and 019 had followed study participants for another year or two, would investigators have seen the Kaplan-Meier survival curves cross–rather than simply converge?

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