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Title: Etravirine and rilpivirine resistance in HIV-1 subtype CRF01-AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens
Authors: Torsak Bunupuradah
Jintanat Ananworanich
Ploenchan Chetchotisakd
Pacharee Kantipong
Supunnee Jirajariyavej
Sunee Sirivichayakul
Warangkana Munsakul
Wisit Prasithsirikul
Somnuek Sungkanuparph
Chureeratana Bowonwattanuwong
Virat Klinbuayaem
Kathy Petoumenos
Bernard Hirschel
Sorakij Bhakeecheep
Kiat Ruxrungtham
The HIV Netherlands Australia Thailand Research Collaboration
University of New South Wales (UNSW) Australia
Chulalongkorn University
Khon Kaen University
Chiangrai Prachanukroh Hospital
Taksin Hospital
Vajira Hospital
Bamrasnaradura Infectious Disease Institute
Mahidol University
Chonburi Regional Hospital
Sanpatong Hospital
Universite de Geneve
National Health Security Office
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 3-Nov-2011
Citation: Antiviral Therapy. Vol.16, No.7 (2011), 1113-1121
Abstract: 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/mm 3 and 4.1 (3.6-4.6) log 10 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 log 10 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 highlevel 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. ©2011 International Medical Press.
ISSN: 13596535
Appears in Collections:Scopus 2011-2015

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