• DOI:10.3851/IMP1906
• Corpus ID: 32181321

Etravirine and Rilpivirine Resistance in HIV-1 Subtype Crf01_Ae-Infected Adults Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens

@article{Bunupuradah2011EtravirineAR,
  title={Etravirine and Rilpivirine Resistance in HIV-1 Subtype Crf01\_Ae-Infected Adults Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens},
  author={Torsak Bunupuradah and Jintanat Ananworanich and Ploenchan Chetchotisakd and Pacharee Kantipong and Supunnee Jirajariyavej and Sunee Sirivichayakul and Warangkana Munsakul and Wisit Prasithsirikul and Somnuek Sungkanuparph and Chureeratana Bowonwattanuwong and Virat Klinbuayaem and Kathy Petoumenos and Bernard Hirschel and Sorakij Bhakeecheep and Kiat Ruxrungtham},
  journal={Antiviral Therapy},
  year={2011},
  volume={16},
  pages={1113 - 1121}
}

• T. Bunupuradah, J. Ananworanich, +12 authors K. Ruxrungtham
• Published 1 October 2011
• Medicine, Biology
• Antiviral Therapy

Background We studied prevalence of etravirine (ETR) and rilpivirine (RPV) resistance in HIV-1 subtype CRF01_AE infection with first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) failure. Methods A total of 225 adults failing two nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 NNRTI in Thailand with HIV RNA>1,000 copies/ml were included. Genotypic resistance results and HIV-1 subtype were interpreted by Stanford DR database. ETR resistance was calculated by the new Monogram weighted score (Monogram WS; ≥4 indicating high-level ETR resistance) and by DUET weighted score (DUET WS; 2.5–3.5 and ≥4 resulted in intermediate and reduce ETR response, respectively). RPV resistance interpretation was based on previous reports. Results Median (IQR) age was 38 (34–42) years, 41% were female and CDC A:B:C were 22%:21%:57%. HIV subtypes were 96% CRF01_AE and 4% B. Antiretrovirals at failure were lamivudine (100%), stavudine (93%), nevirapine (90%) and efavirenz (10%) with a median (IQR) duration of 3.4 (1.8–4.5) years. Median (IQR) CD4+ T-cell count and HIV RNA were 194 (121–280) cells/mm3 and 4.1 (3.6–4.6) log10 copies/ml, respectively. The common NNRTI mutations were Y181C (41%), G190A (22%) and K103N (19%). The proportion of patients with Monogram WS score ≥4 was 61.3%. By DUET WS, 49.8% and 7.5% of patients were scored 2.5–3.5 and ≥4, respectively. Only HIV RNA≥4 log10 copies/ml at failure was associated with both Monogram WS≥4 (OR 2.3, 95% CI 1.3–3.9; P=0.003) and DUET WS≥2.5 (OR 1.9, 95% CI 1.1–3.3; P=0.02). The RVP resistance-associated mutations (RAMs) detected were K101P (1.8%), Y181I (2.7%) and Y181V (3.6%). All patients with RPV mutation had ETR resistance. No E138R/E138K mutations were detected. Conclusions Approximately 60% of patients had high-level ETR resistance. The role of ETR in second-line therapy is limited in late NNRTI failure settings. RVP RAMs were uncommon, but cross-resistance between ETR and RVP was high.