TY - JOUR
T1 - Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine
AU - Nagarajan, Pavithra
AU - Zhou, Jinru
AU - Di Teodoro, Giulia
AU - Incardona, Francesca
AU - Seguin-Devaux, Carole
AU - Kaiser, Rolf
AU - Abecasis, Ana B
AU - Gomes, Perpetua
AU - Tao, Kaiming
AU - Zazzi, Maurizio
AU - Shafer, Robert W
AU - EuResist Network
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/10/31
Y1 - 2024/10/31
N2 - INTRODUCTION: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV).METHODS: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI.RESULTS: Among the 395 PLWH receiving RPV, 180 (45.6%) had one or more NNRTI-associated DRMs. Overall, 44 NNRTI-associated DRMs were identified, including 26 that occurred in two or more PLWHs. Seven mutations had a prevalence ≥10% among the 180 PLWH with one or more NNRTI-associated DRM: E138K (32.2%), V90I (25.0%), K101E (17.8%), Y181C (17.2%), E138A (13.9%), H221Y (12.2%), and K103N (10.6%). Y181C was significantly more likely to co-occur with K101E, V179F, H221Y, and M230L. Ten novel non-polymorphic mutations at known NNRTI-associated mutation positions were also identified, usually in just one PLWH: L100F, V108A, T139I, P225S, M230V, Y232C, and T240A/I/M/S.CONCLUSIONS: Our analysis extends the spectrum of mutations emerging in PLWH receiving RPV. Additional phenotypic characterization of RPV-selected mutations is necessary to better understand their biological and possible clinical significance.
AB - INTRODUCTION: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV).METHODS: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI.RESULTS: Among the 395 PLWH receiving RPV, 180 (45.6%) had one or more NNRTI-associated DRMs. Overall, 44 NNRTI-associated DRMs were identified, including 26 that occurred in two or more PLWHs. Seven mutations had a prevalence ≥10% among the 180 PLWH with one or more NNRTI-associated DRM: E138K (32.2%), V90I (25.0%), K101E (17.8%), Y181C (17.2%), E138A (13.9%), H221Y (12.2%), and K103N (10.6%). Y181C was significantly more likely to co-occur with K101E, V179F, H221Y, and M230L. Ten novel non-polymorphic mutations at known NNRTI-associated mutation positions were also identified, usually in just one PLWH: L100F, V108A, T139I, P225S, M230V, Y232C, and T240A/I/M/S.CONCLUSIONS: Our analysis extends the spectrum of mutations emerging in PLWH receiving RPV. Additional phenotypic characterization of RPV-selected mutations is necessary to better understand their biological and possible clinical significance.
KW - HIV-1 drug resistance
KW - non-nucleoside reverse transcriptase inhibitors
KW - rilpivirine
KW - Reverse Transcriptase Inhibitors/therapeutic use
KW - Humans
KW - Middle Aged
KW - Anti-HIV Agents/therapeutic use
KW - Genotype
KW - Male
KW - Rilpivirine/therapeutic use
KW - HIV Infections/drug therapy
KW - Drug Resistance, Viral/genetics
KW - HIV-1/genetics
KW - Female
KW - Adult
KW - HIV Reverse Transcriptase/genetics
KW - Mutation
UR - https://pubmed.ncbi.nlm.nih.gov/39599830/
U2 - 10.3390/v16111715
DO - 10.3390/v16111715
M3 - Article
C2 - 39599830
SN - 1999-4915
VL - 16
JO - Viruses
JF - Viruses
IS - 11
M1 - 1715
ER -