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Education > Clinical Updates

Clinical Update 9 - News from the 15^th Conference on Retroviruses and Opportunistic Infections

Boston, Massachusetts
February 3-7, 2008

Etravirine (TMC125), a new next-generation NNRTI, shows antiviral activity in treatment-experienced adult patients with HIV resistant to a NNRTI and other antiretroviral agents.  Data from the DUET trials showed that patients with >3 etravirine resistance-associated mutations (RAMs, V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, G190A/S) at baseline had a diminished virologic response to etravirine.  Gaston Picchio from Tibotec, in collaboration with colleagues from Tibotec and Virco, presented data at the 15^th Conference on Retroviruses and Opportunistic Infections on the prevalence of etravirine RAMS among 226,491 routine clinical samples submitted to Virco between January 1999 and June 2007.  They found that the coexistence of >3 etravirine resistance-associated mutations was infrequent, even in patients with evidence of resistance to first-generation NNRTIs.

A total of 226,491 routine clinical isolates (excluding samples collected during clinical trials) were examined.  NNRTI resistance was defined by the presence of either >1 NNRTI IAS-USA mutations (September 2006) or if the predicted fold-change value for any approved NNRTI (excluding etravirine) was greater than the respective virco®TYPE HIV-1 biological cut-off.  NNRTI resistance was identified in 39% and 42% of samples by the IAS USA criteria and BCO definition, respectively.

Among the subset of samples with NNRTI resistance, approximately 40% had no detectable etravirine resistance-associated mutations.  In the subset of samples evaluated using the IAS-USA criteria (n=89,113), only 7.3% of the samples with baseline resistance to first generation NNRTIs had ≥ 3 etravirine RAMs. The prevalence of samples with either 1 or 2 etravirine mutations was 36.7% and 16%, respectively.  The most frequently occurring etravirine resistance-associated mutations were Y181C (27.6%) and G190A (21.1%) regardless of the presence of other etravirine RAMs.   Among isolates with two etravirine RAMs (N=14,919), the most common combinations were Y181C + G190A (27.1%), K101E + G190A (12.5%), and V90I + Y181C (7.0%).  Among isolates with three etravirine RAMs (N = 5,370) the most frequently observed combination was K101E + Y181C + G190A (34%).  It should be noted that the etravirine resistance-associated mutations associated with the greatest negative impact on response in the DUET studies (V179D/F, Y181V, and G190S) exhibited some of the lowest prevalence rates among the routine clinical samples tested, ranging from 0.4% to 4.3%.

Data from this analysis also found that the proportion of NNRTI resistant samples with no etravirine resistance-associated mutations increased over time while the proportion with certain etravirine resistance-associated mutations decreased.  If you are interested in viewing the complete poster, please click here.

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