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Hitting it Early, Hard: The Aftermath

The Fickle (and Unforgiving) Fashion of Antiretroviral Therapies:

Early treatment choices and their unintended consequences.

'Early' AZT
1990
No survival benefit found; resistant mutant associated with more rapid progression.
AZT+3TC
1994
Double resistance after one year; reduced sensitivity to other nucleoside reverse transcriptase inhibitors.
AZT+ddI
1995
Combination not proven superior to ddI monotherapy; AZT mutant not forestalled. Selection of multi-ddN resistant mutants.
AZT+3TC+IDV
1996
Indinavir "break-throughs" highly resistant to other proteases; resistant mutants fully 'fit.'