BACKGROUND: Recent data suggest that subjects harbouring low-frequency variants of HIV that are resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) could suffer virological failure when treated with NNRTI-based therapy. Rilpivirine, a second-generation NNRTI, will be used in first-line regimen therapy, but the prevalence of minority variants that are resistant to rilpivirine is unknown. OBJECTIVES: We evaluated the presence of low-frequency NNRTI resistance associated mutations (RAMs) in 27 patients with a primary HIV-1 infection. STUDY DESIGN: We performed genotypic resistance test at baseline and used ultradeep pyrosequencing (UDPS) to detect minority RAMs. RESULTS: Bulk genotyping identified NNRTI-resistant RAMs in 3/27 (11%) patients while UDPS identified NNRTI-resistant RAMs in 10/27 (37%) patients. The 11 RAMs not detected by bulk sequencing were A98G (n=2), L100I (n=3), K101E (n=2), V106I (n=3) and E138G (n=1). The prevalence of these minority variants was 0.34-18.26%. The absolute copy numbers of minority resistant variants were 3.21-5.53 log copies/mL. CRF02 harboured more minority resistant variants than subtypes B (P<0.05). Four samples (15%) had a major rilpivirine resistant mutation (E138G, K101E and E138A), 3 of which were detected by UDPS. CONCLUSION: In these primary HIV infected patients, as regards to the detection of RAMs at the cut-off level>15-25% of the virus population, the concordance between bulk genotypic and UDPS was perfect. UDPS detected additional major NNRTI-resistant mutations, including rilpivirine resistant variants. Further studies are needed to assess the impact of these minority variants on treatment efficacy.
BACKGROUND: Recent data suggest that subjects harbouring low-frequency variants of HIV that are resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) could suffer virological failure when treated with NNRTI-based therapy. Rilpivirine, a second-generation NNRTI, will be used in first-line regimen therapy, but the prevalence of minority variants that are resistant to rilpivirine is unknown. OBJECTIVES: We evaluated the presence of low-frequency NNRTI resistance associated mutations (RAMs) in 27 patients with a primary HIV-1 infection. STUDY DESIGN: We performed genotypic resistance test at baseline and used ultradeep pyrosequencing (UDPS) to detect minority RAMs. RESULTS: Bulk genotyping identified NNRTI-resistant RAMs in 3/27 (11%) patients while UDPS identified NNRTI-resistant RAMs in 10/27 (37%) patients. The 11 RAMs not detected by bulk sequencing were A98G (n=2), L100I (n=3), K101E (n=2), V106I (n=3) and E138G (n=1). The prevalence of these minority variants was 0.34-18.26%. The absolute copy numbers of minority resistant variants were 3.21-5.53 log copies/mL. CRF02 harboured more minority resistant variants than subtypes B (P<0.05). Four samples (15%) had a major rilpivirine resistant mutation (E138G, K101E and E138A), 3 of which were detected by UDPS. CONCLUSION: In these primary HIV infectedpatients, as regards to the detection of RAMs at the cut-off level>15-25% of the virus population, the concordance between bulk genotypic and UDPS was perfect. UDPS detected additional major NNRTI-resistant mutations, including rilpivirine resistant variants. Further studies are needed to assess the impact of these minority variants on treatment efficacy.
Authors: Ivo N SahBandar; Genesis Samonte; Elizabeth Telan; Nalyn Siripong; Mahdi Belcaid; David Schanzenbach; Susan Leano; Haorile Chagan-Yasutan; Toshio Hattori; Cecilia M Shikuma; Lishomwa C Ndhlovu Journal: AIDS Res Hum Retroviruses Date: 2017-07-05 Impact factor: 2.205
Authors: Herbert A Mbunkah; Silvia Bertagnolio; Raph L Hamers; Gillian Hunt; Seth Inzaule; Tobias F Rinke De Wit; Roger Paredes; Neil T Parkin; Michael R Jordan; Karin J Metzner Journal: J Infect Dis Date: 2020-04-27 Impact factor: 5.226
Authors: Elizabeth P St John; Birgitte B Simen; Gregory S Turenchalk; Michael S Braverman; Isabella Abbate; Jeroen Aerssens; Olivier Bouchez; Christian Gabriel; Jacques Izopet; Karolin Meixenberger; Francesca Di Giallonardo; Ralph Schlapbach; Roger Paredes; James Sakwa; Gudrun G Schmitz-Agheguian; Alexander Thielen; Martin Victor; Karin J Metzner; Martin P Däumer Journal: PLoS One Date: 2016-01-12 Impact factor: 3.240
Authors: Zou Xiaobai; Chen Xi; Hongping Tian; Ann B Williams; Honghong Wang; Jianmei He; Jun Zhen; Jennifer Chiarella; Lisebeth A Blake; Gregory Turenchalk; Michael J Kozal Journal: PLoS One Date: 2014-06-04 Impact factor: 3.240