Drug resistance profile of integrase inhibitors when treating HIV-2

Simon Collins, HIV i-Base

Treatment guidelines for HIV-1 have for many years recommended integrase inhibitor-based ART as first-line ART.

A study just published in JID includes an analysis of drug resistance mutations that are specific to HIV-2, with significant loss in phenotypic sensitivity.

These will be an essential reference for optimal management of HIV-2 where maintaining sensitivity to integrase inhibitors will be essential for long-term care.

The abstract results note: “We observed extensive cross-resistance between raltegravir and dolutegravir in HIV-2_ROD9. HIV-2–specific integrase mutations Q91R, E92A, A153G, and H157Q/S, which have not been previously characterised, significantly increased the EC₅₀ for raltegravir when introduced into one or more mutational backgrounds; mutations E92A/Q, T97A, and G140A/S conferred similar enhancements of dolutegravir resistance. HIV-2_ROD9 variants encoding G118R alone, or insertions of residues SREGK or SREGR at position 231, were resistant to both INIs.”

Reference

Smith RA et al for the University of Washington-Senegal HIV-2 Study Group. Spectrum of activity of raltegravir and dolutegravir against novel treatment-associated mutations in HIV-2 integrase: A phenotypic analysis using an expanded panel of site-directed mutants, Journal of Infectious Diseases, 2022; jiac037. DOI: 10.1093/infdis/jiac037. (3 February 2022).
https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiac037/6521074