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

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

doi:10.1093/infdis/jiaa026

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

J Infect Dis. 2020 Jun 11;221(12):1962-1972. doi: 10.1093/infdis/jiaa026.

Authors

Philip L Tzou¹, Diane Descamps^{2

3}, Soo-Yon Rhee¹, Dana N Raugi⁴, Charlotte Charpentier^{2

3}, Nuno Taveira^{5

6}, Robert A Smith⁴, Vicente Soriano⁷, Carmen de Mendoza⁸, Susan P Holmes⁹, Geoffrey S Gottlieb^{4

10}, Robert W Shafer¹

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA.
² Laboratoire de Virologie, Hôpital Bichat-Claude Bernard, APHP.Nord Universite de Paris, France.
³ INSERM UMR 1137, Paris, France.
⁴ Department of Medicine, University of Washington, Seattle, Washington, USA.
⁵ Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
⁶ Instituto Universitário Egas Moniz, Monte da Caparica, Portugal.
⁷ Health Sciences School and Medical Center, Universidad Internacional de La Rioja, Madrid, Spain.
⁸ Puerta de Hierro University Hospital and Research Institute, Madrid, Spain.
⁹ Department of Statistics, Stanford University, Stanford, California, USA.
¹⁰ Department of Global Health, University of Washington, Seattle, Washington, USA.

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.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural

MeSH terms

Amino Acid Substitution
Drug Resistance, Viral / genetics*
HIV Infections / drug therapy*
HIV Infections / virology
HIV Protease / genetics*
HIV Protease Inhibitors / pharmacology*
HIV Protease Inhibitors / therapeutic use
HIV Reverse Transcriptase / antagonists & inhibitors
HIV Reverse Transcriptase / genetics*
HIV-2 / drug effects
HIV-2 / genetics*
Humans
Mutation / drug effects

Substances

HIV Protease Inhibitors
HIV Reverse Transcriptase
HIV Protease

Abstract

Publication types

MeSH terms

Substances

Grants and funding