OBJECTIVES: The prevalence of rilpivirine, emtricitabine and tenofovir resistance-associated mutations (RAMs), described in vitro and in vivo, was determined in antiretroviral-naive patients. PATIENTS AND METHODS: From 2008 to 2011, 1729 treatment-naive patients were tested for resistance by bulk sequencing. We studied the primary rilpivirine RAMs (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C and M230I/L) and other potential rilpivirine-associated mutations (V90I, L100I, K101T, E138S, V179D/I, Y188L, V189I, G190A/E/S and M230V). We also studied the M184V/I and K65R mutations for emtricitabine and tenofovir, respectively. RESULTS: Among 1729 sequences, half of patients had B-subtype viruses and the other half non-B (with 26.7% CRF02, n=461). Primary rilpivirine RAMs were infrequent (4.6%, n=79) and the most prevalent were E138A (3%, n=52), E138K, (0.3%, n=5), H221Y (0.3%, n=5), E138G (0.2%, n=4) and Y181C (0.2%, n=4). The frequency of the primary rilpivirine RAMs was similar between B and non-B subtypes. The other potential rilpivirine-associated mutations that were most prevalent were V179I (8.4%, n=145), V90I (3.8%, n=65) and V189I (2.3%, n=40). The common V179I, V189I and V90I polymorphisms have not been associated with virological failure in Phase 3 clinical studies. By the ANRS algorithm, 4.9% (n=84) of samples were resistant to rilpivirine, 3.7% (n=32) of B-subtype viruses versus 6% (n=52) of non-B-subtype viruses (P=0.02, χ(2) test). The prevalence of K65R and M184I/V was 0.06% (1/1729) and 1% (18/1729), respectively. The prevalence of K103N was 2% (35/1729). CONCLUSIONS: The prevalence of rilpivirine, emtricitabine and tenofovir resistance mutations was very low in antiretroviral-naive patients. The prevalence of resistance to rilpivirine (4.9%, n=84) was not statistically different from the prevalence of efavirenz and nevirapine resistance in our population.
OBJECTIVES: The prevalence of rilpivirine, emtricitabine and tenofovir resistance-associated mutations (RAMs), described in vitro and in vivo, was determined in antiretroviral-naive patients. PATIENTS AND METHODS: From 2008 to 2011, 1729 treatment-naive patients were tested for resistance by bulk sequencing. We studied the primary rilpivirine RAMs (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C and M230I/L) and other potential rilpivirine-associated mutations (V90I, L100I, K101T, E138S, V179D/I, Y188L, V189I, G190A/E/S and M230V). We also studied the M184V/I and K65R mutations for emtricitabine and tenofovir, respectively. RESULTS: Among 1729 sequences, half of patients had B-subtype viruses and the other half non-B (with 26.7% CRF02, n=461). Primary rilpivirine RAMs were infrequent (4.6%, n=79) and the most prevalent were E138A (3%, n=52), E138K, (0.3%, n=5), H221Y (0.3%, n=5), E138G (0.2%, n=4) and Y181C (0.2%, n=4). The frequency of the primary rilpivirine RAMs was similar between B and non-B subtypes. The other potential rilpivirine-associated mutations that were most prevalent were V179I (8.4%, n=145), V90I (3.8%, n=65) and V189I (2.3%, n=40). The common V179I, V189I and V90I polymorphisms have not been associated with virological failure in Phase 3 clinical studies. By the ANRS algorithm, 4.9% (n=84) of samples were resistant to rilpivirine, 3.7% (n=32) of B-subtype viruses versus 6% (n=52) of non-B-subtype viruses (P=0.02, χ(2) test). The prevalence of K65R and M184I/V was 0.06% (1/1729) and 1% (18/1729), respectively. The prevalence of K103N was 2% (35/1729). CONCLUSIONS: The prevalence of rilpivirine, emtricitabine and tenofovir resistance mutations was very low in antiretroviral-naive patients. The prevalence of resistance to rilpivirine (4.9%, n=84) was not statistically different from the prevalence of efavirenz and nevirapine resistance in our population.
Authors: Ujjwal Neogi; Amanda Häggblom; Kamalendra Singh; Leonard C Rogers; Shwetha D Rao; Wondwossen Amogne; Eugen Schülter; Maurizio Zazzi; Eddy Arnold; Stefan G Sarafianos; Anders Sönnerborg Journal: J Antimicrob Chemother Date: 2015-10-30 Impact factor: 5.790
Authors: Na Liu; Lei Wei; Li Huang; Fei Yu; Weifan Zheng; Bingjie Qin; Dong-Qin Zhu; Susan L Morris-Natschke; Shibo Jiang; Chin-Ho Chen; Kuo-Hsiung Lee; Lan Xie Journal: J Med Chem Date: 2016-04-12 Impact factor: 7.446
Authors: Hiroyuki Gatanaga; Zabrina L Brumme; Emily Adland; Gustavo Reyes-Terán; Santiago Avila-Rios; Carlos R Mejía-Villatoro; Tsunefusa Hayashida; Takayuki Chikata; Giang Van Tran; Kinh Van Nguyen; Rita I Meza; Elsa Y Palou; Humberto Valenzuela-Ponce; Juan M Pascale; Guillermo Porras-Cortés; Marvin Manzanero; Guinevere Q Lee; Jeffrey N Martin; Mary N Carrington; Mina John; Simon Mallal; Art F Y Poon; Philip Goulder; Masafumi Takiguchi; Shinichi Oka Journal: AIDS Date: 2017-09-10 Impact factor: 4.177
Authors: Kristof Theys; Kristel Van Laethem; Perpetua Gomes; Guy Baele; Andrea-Clemencia Pineda-Peña; Anne-Mieke Vandamme; Ricardo J Camacho; Ana B Abecasis Journal: AIDS Res Hum Retroviruses Date: 2016-01-29 Impact factor: 2.205
Authors: Lei Wei; Hui-Ling Wang; Li Huang; Chin-Ho Chen; Susan L Morris-Natschke; Kuo-Hsiung Lee; Lan Xie Journal: Bioorg Med Chem Lett Date: 2017-04-22 Impact factor: 2.823