Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens

• Published in: Antiviral therapy Vol. 16; no. 7; pp. 1113 - 1121
• Main Authors: BUNUPURADAH, Torsak, ANANWORANICH, Jintanat, KLINBUAYAEM, Virat, PETOUMENOS, Kathy, HIRSCHEL, Bernard, BHAKEECHEEP, Sorakij, RUXRUNGTHAM, Kiat, CHETCHOTISAKD, Ploenchan, KANTIPONG, Pacharee, JIRAJARIYAVEJ, Supunnee, SIRIVICHAYAKUL, Sunee, MUNSAKUL, Warangkana, PRASITHSIRIKUL, Wisit, SUNGKANUPARPH, Somnuek, BOWONWATTANUWONG, Chureeratana
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.01.2011
• Subjects: Adult; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active; Antiviral agents; Benzoxazines - administration & dosage; Benzoxazines - pharmacology; Benzoxazines - therapeutic use; Biological and medical sciences; Drug Resistance, Viral; Female; Genotype; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - classification; HIV-1 - drug effects; HIV-1 - genetics; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lamivudine - administration & dosage; Lamivudine - pharmacology; Lamivudine - therapeutic use; Male; Medical sciences; Mutation; Nevirapine - administration & dosage; Nevirapine - pharmacology; Nevirapine - therapeutic use; Nitriles - administration & dosage; Nitriles - pharmacology; Nitriles - therapeutic use; Pharmacology. Drug treatments; Pyridazines - administration & dosage; Pyridazines - pharmacology; Pyridazines - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Rilpivirine; RNA, Viral - blood; Stavudine - administration & dosage; Stavudine - pharmacology; Stavudine - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Antiretroviral agent; RNA-directed DNA polymerase; HIV-1 virus; Rilpivirine; Non nucleoside compound; Reverse transcriptase inhibitor; Adult; Antiviral; Human; Immunopathology; Typing; Enzyme; Transferases; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Resistance; Nucleotidyltransferases; Viral disease; Etravirine; Human immunodeficiency virus; Subtype
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/imp1906

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. 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. 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. 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.