New HIV Drug Concern: How can long term survivors with archived NNRTI resistance know if Intelence is really an “intelligent” choice ?Nelson Vergel
Intelence (TMC 125- etravirine) is a new NNRTI just approved today for the treatment of HIV.
Many of us developed resistance to Nevirapine and Efavirenz years ago and are now showing “sensitivity” to NNRTIs after years of not taking them since NNRTI resistance gets archived after years. Many of the key resistance mutations that render TMC 125 useless were not listed in old genotypes that doctors can pull from our old records,so we do not really know if this new NNRTI will be an active agent for us. I am R5 tropic and need at least one (preferably two) more active agents.
Question: How can long term survivors with archived NNRTI resistance from years ago know if Intelence is really an “intelligent” choice for them as part of a 2 or 3 active drug regimen?
These are the key mutations they list:
— The presence of K103N, which was the most prevalent NNRTI substitution in DUET-1 and -2 studies at baseline, did not affect the response in the INTELENCE arm.
— The presence at baseline of the substitutions V179D, V179F, V179T,
Y181V, or G190S was associated with a decreased virologic response to INTELENCE.
— In the DUET-1 and -2 studies, the presence at baseline of three or more 2007 IAS-USA-defined NNRTI substitutions (V90I, A98G, L100I, K101E/P, K103N, V106A/I/M, V108I, V179D/F, Y181C/I/V, Y188C/H/L, G190A/S, P225H) resulted in a decreased virologic response to INTELENCE.
— For patients in the DUET-1 and -2 studies experiencing virologic
failure on an INTELENCE-containing regimen, the substitutions that
occurred most commonly were V179F, V179I, Y181C, and Y181I which usually emerged in a background of multiple other NNRTI resistance-associated substitutions. Other NNRTI resistance-associated substitutions which emerged in patients on INTELENCE treatment in
< 10 percent of the virologic failure isolates included K101E, K103N,
V106I/M, V108I, Y188L, V189I, G190S/C and R356K.
— Cross-resistance to delavirdine, efavirenz, and/or nevirapine is
expected after virologic failure with an INTELENCE-containing regimen.