Details

Autor(en) / Beteiligte

• Tzou, Philip L
• Descamps, Diane
• Rhee, Soo-Yon
• Raugi, Dana N
• Charpentier, Charlotte
• Taveira, Nuno
• Smith, Robert A
• Soriano, Vicente
• de Mendoza, Carmen
• Holmes, Susan P
• Gottlieb, Geoffrey S
• Shafer, Robert W

Titel

Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2

Ist Teil von

• The Journal of infectious diseases, 2020-06, Vol.221 (12), p.1962-1972

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2020

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Background HIV-1 and HIV-2 differ in their antiretroviral (ARV) susceptibilities and drug resistance mutations (DRMs). Methods We analyzed published HIV-2 pol sequences to identify HIV-2 treatment-selected mutations (TSMs). Mutation prevalences were determined by HIV-2 group and ARV status. Nonpolymorphic mutations were those in <1% of ARV-naive persons. TSMs were those associated with ARV therapy after multiple comparisons adjustment. Results We analyzed protease (PR) sequences from 483 PR inhibitor (PI)-naive and 232 PI-treated persons; RT sequences from 333 nucleoside RT inhibitor (NRTI)-naive and 252 NRTI-treated persons; and integrase (IN) sequences from 236 IN inhibitor (INSTI)-naive and 60 INSTI-treated persons. In PR, 12 nonpolymorphic TSMs occurred in ≥11 persons: V33I, K45R, V47A, I50V, I54M, T56V, V62A, A73G, I82F, I84V, F85L, L90M. In RT, 9 nonpolymorphic TSMs occurred in ≥10 persons: K40R, A62V, K70R, Y115F, Q151M, M184VI, S215Y. In IN, 11 nonpolymorphic TSMs occurred in ≥4 persons: Q91R, E92AQ, T97A, G140S, Y143G, Q148R, A153G, N155H, H156R, R231 5-amino acid insertions. Nine of 32 nonpolymorphic TSMs were previously unreported. Conclusions This meta-analysis confirmed the ARV association of previously reported HIV-2 DRMs and identified novel TSMs. Genotypic and phenotypic studies of HIV-2 TSMs will improve approaches to predicting HIV-2 ARV susceptibility and treating HIV-2–infected persons. This meta-analysis of HIV-2 protease, reverse transcriptase, and integrase mutations in sequences from antiretroviral naive and treated persons identified established and novel antiretroviral-selected mutations. These results will improve HIV-2 antiretroviral susceptibility prediction and prioritize HIV-2 resistance mutations for phenotypic studies.