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Using the latest resistance score to predict etravirine (ETV) resistance in naïve and NNRTI-failing patients
Journal of the International AIDS Society volume 11, Article number: P179 (2008)
Purpose of the study
To assess the feasibility of a rescue ETV-containing cART regimen in naïve patients with primary NNRTI resistance mutations or after first NNRTI failure, using the latest resistance score presented.
A set of 17 mutations (V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S, M230L) were found associated with ETV resistance in the Phase III DUET-1 and DUET-2 trials. Recently, a different score was assigned to each mutation (i.e. Y181C/I have the highest score: 3). An overall score of ≤4 was associated with reduced response and a score between 2.5–3.5 with intermediate response (reference). ETV resistance was calculated from a large database of patients undergoing genotypic resistance test.
Overall, 241 ARV-naïve patients and 311 failing a first NNRTI regimen (EFV = 189, NVP = 122) were analyzed. Among naïve patients, 14 (5.8%) harbored ≤1 major NNRTI resistance mutation but only in one patient (0.4%) a ≤4 score, and in five patients (2.1%) a score between 2.5–3.5 were detected.
Among failing patients, two-thirds harbored major NNRTI mutations (about half had K103N). In contrast, a ≤4 score was found in 5.8% of patients, with similar proportion in EFV- and NVP-treated patients (5.8% vs. 5.7%), though among NVP patients a score between 2.5–3.5 was more frequently found (28.7% vs. 20.1%).
The probability of developing a ≤4 score was 0.0% during the first 3 months of NNRTI failure and 3.1% between 3–6 months (2.6% in EFV vs. 3.9% in NVP failure). Subsequently, during EFV failure, the probability of developing a ≤4 score increased between 6–12 months to 20.0% (particularly between 9–12 months: 23.5%) and during NVP failure, between 9–12 months to 9.1%.
At adjusted logistic regression, remaining in NNRTI failure between 6–12 months was the only factor associated to developing a ≤4 ETV score (OR: 22.0, 95& CI: 2.65–182.89, p = 0.004).
The presence of mutations predictive of full or intermediate ETV resistance is uncommon among naïve patients, thus, in almost all cases, ETV use may be allowed. The detection of ETV-resistance is also infrequent in patients failing a NNRTI regimen because usually they develop the K103N mutation, that alone or in combination does not affect ETV sensitivity. Our data also suggest that a quick withdrawal of a failing NNRTI regimen, possibly in the first 3 months of failure, can maintain ETV sensitivity, thus preserving a treatment option.
Vingerhoets J, et al: An update of the list of NNRTI mutations associated with decreased virological response to etravirine: multivariate analysis of the pooled DUET-1 and DUET-2 clinical trial data. [XVII International Drug Resistance Workshop, June 10–14, Sitges, Spain; Abstract 24]. Antivir Therapy. 2008, 13 (Suppl 3): A26-
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Zaccarelli, M., Lorenzini, P., Ceccherini-Silberstein, C. et al. Using the latest resistance score to predict etravirine (ETV) resistance in naïve and NNRTI-failing patients. JIAS 11 (Suppl 1), P179 (2008). https://doi.org/10.1186/1758-2652-11-S1-P179
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