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Open Forum Infect Dis
. 2024 Jul 2;11(7):ofae344.
doi: 10.1093/ofid/ofae344. eCollection 2024 Jul. Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana
Wonderful T Choga 1 2 , Ontlametse T Bareng 1 2 , Natasha O Moraka 1 2 , Dorcas Maruapula 1 , Irene Gobe 2 , Nokuthula S Ndlovu 1 3 , Boitumelo J L Zuze 1 , Patience C Motshosi 1 , Kedumetse B Seru 1 , Teko Matsuru 1 , Matshwenyego Boitswarelo 4 , Mogomotsi Matshaba 5 6 , Tendani Gaolathe 1 7 , Mosepele Mosepele 1 7 , Joseph Makhema 1 8 , Trevor J M Tamura 9 , Jonathan Z Li 9 , Roger Shapiro 1 8 , Shahin Lockman 1 8 10 , Simani Gaseitsiwe 1 8 , Sikhulile Moyo 1 2 8 11 12
Affiliations
Background: We evaluated naturally occurring nirmatrelvir-ritonavir (NTV/r) resistance-associated mutations (RAMs) among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Botswana, a country with no NTV/r use to date, in order to recommend the usage of the agent for high-risk patients with coronavirus disease 2019 (COVID-19).
Methods: We conducted a retrospective analysis using 5254 complete SARS-CoV-2 sequences from Botswana (September 2020-September 2023). We evaluated the mutational landscape of SARS-CoV-2 3-Chymotrypsin-like protease (3CLpro) relative to the highlighted list of RAMs granted Food and Drug Administration Emergency Use Authorization in 2023.
Results: The sequenced 5254 samples included Beta variants of concerns (VOCs; n = 323), Delta VOCs (n = 1314), and Omicron VOCs (n = 3354). Overall, 77.8% of the sequences exhibited at least 1 polymorphism within 76/306 amino acid positions in the nsp5 gene. NTV/rRAMs were identified in 34/5254 (0.65%; 95% CI, 0.43%-0.87%) and occurred at 5 distinct positions. Among the NTV/r RAMS detected, A191V was the most prevalent (24/34; 70.6%). Notably, T21I mutation had a prevalence of 20.6% (7/34) and coexisted with either K90R (n = 3) polymorphism in Beta sequences with RAMs or P132H (n = 3) polymorphism for Omicron sequences with RAMs. Other NTV/r RAMs detected included P108S, with a prevalence of 5.88% (2/34), and L50F, with a prevalence of 2.94% (1/34). NTV/r RAMs were significantly higher (P < .001) in Delta (24/35) compared with Beta (4/34) and Omicron (6/34) sequences.
Conclusions: The frequency of NTV/r RAMs in Botswana was low. Higher rates were observed in Delta VOCs compared to Omicron and Beta VOCs. As NTV/r use expands globally, continuous surveillance for drug-resistant variants is essential, given the RAMs identified in our study.
Keywords: Botswana; Paxlovid; SARS-CoV-2; nirmatrelvir-ritonavir; resistance mutations.
. 2024 Jul 2;11(7):ofae344.
doi: 10.1093/ofid/ofae344. eCollection 2024 Jul. Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana
Wonderful T Choga 1 2 , Ontlametse T Bareng 1 2 , Natasha O Moraka 1 2 , Dorcas Maruapula 1 , Irene Gobe 2 , Nokuthula S Ndlovu 1 3 , Boitumelo J L Zuze 1 , Patience C Motshosi 1 , Kedumetse B Seru 1 , Teko Matsuru 1 , Matshwenyego Boitswarelo 4 , Mogomotsi Matshaba 5 6 , Tendani Gaolathe 1 7 , Mosepele Mosepele 1 7 , Joseph Makhema 1 8 , Trevor J M Tamura 9 , Jonathan Z Li 9 , Roger Shapiro 1 8 , Shahin Lockman 1 8 10 , Simani Gaseitsiwe 1 8 , Sikhulile Moyo 1 2 8 11 12
Affiliations
- PMID: 39015352
- PMCID: PMC11250512
- DOI: 10.1093/ofid/ofae344
Background: We evaluated naturally occurring nirmatrelvir-ritonavir (NTV/r) resistance-associated mutations (RAMs) among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Botswana, a country with no NTV/r use to date, in order to recommend the usage of the agent for high-risk patients with coronavirus disease 2019 (COVID-19).
Methods: We conducted a retrospective analysis using 5254 complete SARS-CoV-2 sequences from Botswana (September 2020-September 2023). We evaluated the mutational landscape of SARS-CoV-2 3-Chymotrypsin-like protease (3CLpro) relative to the highlighted list of RAMs granted Food and Drug Administration Emergency Use Authorization in 2023.
Results: The sequenced 5254 samples included Beta variants of concerns (VOCs; n = 323), Delta VOCs (n = 1314), and Omicron VOCs (n = 3354). Overall, 77.8% of the sequences exhibited at least 1 polymorphism within 76/306 amino acid positions in the nsp5 gene. NTV/rRAMs were identified in 34/5254 (0.65%; 95% CI, 0.43%-0.87%) and occurred at 5 distinct positions. Among the NTV/r RAMS detected, A191V was the most prevalent (24/34; 70.6%). Notably, T21I mutation had a prevalence of 20.6% (7/34) and coexisted with either K90R (n = 3) polymorphism in Beta sequences with RAMs or P132H (n = 3) polymorphism for Omicron sequences with RAMs. Other NTV/r RAMs detected included P108S, with a prevalence of 5.88% (2/34), and L50F, with a prevalence of 2.94% (1/34). NTV/r RAMs were significantly higher (P < .001) in Delta (24/35) compared with Beta (4/34) and Omicron (6/34) sequences.
Conclusions: The frequency of NTV/r RAMs in Botswana was low. Higher rates were observed in Delta VOCs compared to Omicron and Beta VOCs. As NTV/r use expands globally, continuous surveillance for drug-resistant variants is essential, given the RAMs identified in our study.
Keywords: Botswana; Paxlovid; SARS-CoV-2; nirmatrelvir-ritonavir; resistance mutations.