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

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.

Keywords: HIV-2; drug resistance; integrase strand transfer inhibitors; mutations; nucleoside RT inhibitors; protease inhibitors.

Figure 1.

Natural variability of HIV-2 PR in 483 PI-naive persons (A), RT in 333 NRTI-naive persons (B), and IN in 236 INSTI-naive persons (C). Underlined amino acids are consensus HIV-2 mutations that differ from the group M HIV-1 consensus. Mutations in bold black have a frequency above 50% in antiretroviral-naive persons. Mutations in red have a frequency between 10% and 50%. Mutations in blue have a frequency between 1% and 10%. Abbreviations: HIV, human immunodeficiency virus; IN, integrase; INSTI, integrase strand transfer inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; PR, protease; RT, reverse transcriptase.