Seth C Inzaule1,2, Raph L Hamers1,3, Marc Noguera-Julian4,5, Maria Casadellà4, Mariona Parera4, Tobias F Rinke de Wit1,2, Roger Paredes4,5. 1. Department of Global Health, Academic Medical Center of the University of Amsterdam, and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands. 2. Joep Lange Institute, Department of Global Health, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands. 3. Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia, and Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 4. Infectious Diseases Unit & IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain. 5. Universitat de Vic-Universitat Central de Catalunya, C. Sagrada Família 7, 08500 Vic, Catalonia, Spain.
Abstract
Objectives: To investigate the prevalence and patterns of major and accessory resistance mutations associated with integrase strand transfer inhibitors (INSTIs), across diverse HIV-1 subtypes in sub-Saharan Africa. Methods: pol gene sequences were obtained using Illumina next-generation sequencing from 425 INSTI-naive HIV-infected adults from Kenya (21.2%), Nigeria (7.3%), South Africa (22.8%), Uganda (25.2%) and Zambia (23.5%). Drug resistance interpretation was based on the IAS 2017 mutation list and accessory mutations from Stanford HIVdb with resistance penalty scores of ≥10 to at least 1 INSTI. Resistance was further classified based on sensitivity thresholds of ≥20% (Sanger sequencing) and 1%-20% for low-frequency variants (next-generation sequencing). Results: Of 425 genotypes, 48.7% were subtype C, 28.5% A, 10.1% D, 2.8% G and 9.9% were recombinants. Major INSTI resistance mutations were detected only at <20% threshold, at a prevalence of 2.4% (2.5% in subtype A, 2.4% C, 0% D, 8.3% G and 2.4% in recombinants) and included T66A/I (0.7%), E92G (0.5%), Y143C/S (0.7%), S147G (0.2%) and Q148R (0.5%). Accessory mutations occurred at a prevalence of 15.1% at the ≥20% threshold (23.1% in subtype A, 8.7% C, 11.6% D, 25% G and 23.8% in recombinants), and included L74I/M (10.4%), Q95K (0.5%), T97A (4%), E157Q (0.7%) and G163R/K (0.7%). Conclusions: Major INSTI resistance mutations were rare and only occurred at low-level resistance detection thresholds. INSTI-based regimens are expected to be effective across the different major HIV-1 subtypes in the region.
Objectives: To investigate the prevalence and patterns of major and accessory resistance mutations associated with integrase strand transfer inhibitors (INSTIs), across diverse HIV-1 subtypes in sub-Saharan Africa. Methods: pol gene sequences were obtained using Illumina next-generation sequencing from 425 INSTI-naive HIV-infected adults from Kenya (21.2%), Nigeria (7.3%), South Africa (22.8%), Uganda (25.2%) and Zambia (23.5%). Drug resistance interpretation was based on the IAS 2017 mutation list and accessory mutations from Stanford HIVdb with resistance penalty scores of ≥10 to at least 1 INSTI. Resistance was further classified based on sensitivity thresholds of ≥20% (Sanger sequencing) and 1%-20% for low-frequency variants (next-generation sequencing). Results: Of 425 genotypes, 48.7% were subtype C, 28.5% A, 10.1% D, 2.8% G and 9.9% were recombinants. Major INSTI resistance mutations were detected only at <20% threshold, at a prevalence of 2.4% (2.5% in subtype A, 2.4% C, 0% D, 8.3% G and 2.4% in recombinants) and included T66A/I (0.7%), E92G (0.5%), Y143C/S (0.7%), S147G (0.2%) and Q148R (0.5%). Accessory mutations occurred at a prevalence of 15.1% at the ≥20% threshold (23.1% in subtype A, 8.7% C, 11.6% D, 25% G and 23.8% in recombinants), and included L74I/M (10.4%), Q95K (0.5%), T97A (4%), E157Q (0.7%) and G163R/K (0.7%). Conclusions: Major INSTI resistance mutations were rare and only occurred at low-level resistance detection thresholds. INSTI-based regimens are expected to be effective across the different major HIV-1 subtypes in the region.
Authors: Vinie Kouamou; Justen Manasa; David Katzenstein; Alan M McGregor; Chiratidzo E Ndhlovu; Azure T Makadzange Journal: AIDS Date: 2019-09-01 Impact factor: 4.177
Authors: Emmanuel Ndashimye; Mariano Avino; Abayomi S Olabode; Art F Y Poon; Richard M Gibson; Yue Li; Adam Meadows; Christine Tan; Paul S Reyes; Cissy M Kityo; Fred Kyeyune; Immaculate Nankya; Miguel E Quiñones-Mateu; Eric J Arts Journal: J Antimicrob Chemother Date: 2020-12-01 Impact factor: 5.790
Authors: Suzanne M McCluskey; Toby Pepperrell; Andrew Hill; Willem D F Venter; Ravindra K Gupta; Mark J Siedner Journal: AIDS Date: 2021-12-15 Impact factor: 4.177
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: Kate El Bouzidi; Steven A Kemp; Rawlings P Datir; Fati Murtala-Ibrahim; Ahmad Aliyu; Vivian Kwaghe; Dan Frampton; Sunando Roy; Judith Breuer; Caroline A Sabin; Obinna Ogbanufe; Man E Charurat; David Bonsall; Tanya Golubchik; Christophe Fraser; Patrick Dakum; Nicaise Ndembi; Ravindra K Gupta Journal: J Antimicrob Chemother Date: 2020-06-01 Impact factor: 5.790