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early resistance
Jun 30, 2005

you stated in another post: "hit early,hit hard" is balanced against... "...the risk of resistance early in the course of infection if the medication is applied at high CD4 cell counts" could you explain the reasoning behind this?

Woudn't haart, especially if it contained a CCR5 inhibitor or immunomodulator, prevent overall damage to the immune system and preserve CD4 diversity allowing for a better chance to proliferate an effective antibody to the virus.

Thanks

Jim

Response from Dr. Wohl

Dear Jim-

Use of potent HIV therapy early in therapy can be justified by several arguments including the one you make. Specifically, that suppression of viral replication will limit damage caused by the virus to the immune system and allow for a more robust response to HIV and preserve defenses against opportunistic conditions.

However, a potential downside to early therapy is resistance. History demonstrates that most (not all) people on HIV therapies eventually experience viral rebound, typically with mutations. In fact, the proportion of people starting therapy who are undetectable a year later is generally no where near the 80% or so seen in clinical trials. If people develop resistance mutations at higher CD4 cell counts and cycle through successive regimens a possible result can be a genotype full of mutations at a high CD4 and fewer options when the counts start to dip into the red zone.

Now, this failure worry is based on historical data. Fact is, as you suggest, newer therapies that are even more potent are being developed. These may be harder to become resistant to and more forgiving of lapses in adherence. Such regimens, if they are free of long term side effects, could tip the balance way back to early therapy.

DW



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