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Evaluating the Role of Etravirine in the Second-line ART after Failing an Initial NNRTI-based Regimens in a Resource-limited Setting
Somnuek Sungkanuparph*1, W Manosuthi2, S Kiertiburanakul1, B Piyavong1, and W Chantratita1
1Ramathibodi Hosp, Mahidol Univ, Bangkok, Thailand and 2Bamrasnaradura Infectious Diseases Inst, Ministry of Publ Hlth, Nonthaburi, Thailand
Background: Treatment options after failing an
initial regimen of ART in resource-limited settings are markedly limited
because of the extensive cross-resistance to NRTI secondary to late detection
of failure. Etravirine (TMC125) demonstrates activity against NNRTI-resistant
HIV-1 in DUET-1 and DUET-2 study but its efficacy depends on the number of TMC125
resistance-associated mutations (RAM). This study aimed to evaluate the role of
TMC125 in the second-line ART in a resource-limited setting.
Methods: Genotype resistance mutation patterns in a
cohort of HIV-1-infected patients who experienced virological failure from an
initial NNRTI-based regimen during 2004 to 2007 were studied. We focused on TMC125-RAM
previously described: V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, and
G190A/S. Proportion and predicting factors of patients with <3 TMC125-RAM
were evaluated.
Results: There were 158 patients with a mean (SD)
age of 36.5 (7.0) years of whom 65.2% were males; 133 (84.2%) received
nevirapine-based ART; the others received efavirenz-based ART. The median (IQR)
duration of ART prior to failure was 22 (13 to 29) months. The IQR of CD4 cell
count and HIV-1 RNA at the time of virological failure detection were 173 (98
to 261) cells/mm3 and 4.1 (3.7 to 4.7) log copies/mL, respectively. Of
158 patients, 131 (82.9%) had TMC125-RAM, including Y181C/I/V (59.5%), G190A/S (33.5%),
V179D/F (8.4%), V106I (4.4%), V90I (0.8%), A98G (0.8%), L100I (0.8%), K101E/P,
and (0.8%). Of 131 patients with TMC125-RAM, 92 (70.2%) had <3 TMC125-RAM. There
were no differences of demographics, CD4 cell count, and HIV-1 RNA level at the
time of failure between patients with <3 and ≥3 TMC125-RAM (p >0.05).
From logistic regression, there was no clinical factor to predict patients with
<3 TMC125-RAM. Of 92 patients with <3 TMC125-RAM, 69 (75%) had ≥2
active NRTI from the genotype results.
Conclusions: In resource-limited setting, 70% of
patients can use TMC125 in the second-line ART after failing an initial
NNRTI-based regimen and genotype testing is needed to select this group.
Three-fourths of these patients, indicated by genotype results, may be able to
use TMC125 plus 2 active NRTI for the second regimen. This strategy may be an
option for patients who cannot afford or tolerate protease inhibitors. Prospective
study to evaluate this strategy should be conducted in resource-limited setting.
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