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New drugs on horizon?
Feb 26, 2004

I have been reading about 2 new HIV drug classes in development called integrase inhibitors and transcription inhibitors. How far out are these from being viable and effective HIV treatment options?

Also, what is your opinion of using Tenofovir + 3TC + Sustiva as a first-line regemin, rather than AZT + 3TC + Sustiva? I have heard that Tenofovir has fewer serious side effects than AZT.

Thanks.

Response from Dr. Pierone

Transcription is the process by which DNA is transformed into RNA. Reverse transcription is when RNA is converted into DNA. Most of the currently available antiretrovirals are reverse transcriptase inhibitors that prevent HIV RNA from being changed to HIV DNA. Integrase inhibitors block an enzyme (integrase) that enables HIV DNA (after reverse transcription) to get into the host cell DNA.

We have nucleoside reverse transcriptase inhibitors (AZT, ddI, 3TC, etc) and non-nucleoside reverse transcriptase inhibitors (nevirapine, efavirenz) available now. New classes of drugs that block this enzyme are being investigated, but not yet in humans (that I know of). Second generation agents in these current classes are in the pipeline (nukes - Reverset, SPD-754; non-nuke-capravirene, TMC-125) targeting resistant virus.

Integrase inhibitors are being developed. Merck has promising agents (L870,810; L870,812) and Shinogi had one that failed (S-1360) and at least one more in development.

Given the two choices above for first line therapy, my preference would be tenofovir +3TC + Sustiva over AZT +3TC + Sustiva. Tenofovir has fewer side effects than AZT and does not blunt the CD4 count increase. Also, this is a once daily regimen instead of twice daily.



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