HIV Integrase Inhibitors and Risk for Emergent Drug Resistance

Summary and Comment |
July 7, 2017

HIV Integrase Inhibitors and Risk for Emergent Drug Resistance

  1. Charles B. Hicks, MD

The increasing use of HIV integrase inhibitors in antiretroviral therapy has decreased the incidence of new antiretroviral drug resistance in real-world clinic situations. When resistance did emerge, classic risk factors like poor adherence and advanced immunosuppression were often present.

  1. Charles B. Hicks, MD

The British Columbia Centre for Excellence in HIV/AIDS routinely collects data on HIV-1-infected patients in their care, including antiretroviral treatment history, HIV RNA measurements, and the results of HIV resistance testing. Using these data, investigators assessed emergence of new resistance mutations in a retrospective cohort study of 928 adult HIV-infected patients initiating 985 distinct treatment regimens, each consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and an integrase inhibitor (INSTI) — raltegravir (270), elvitegravir (323), or dolutegravir (392).

Emergent integrase resistance in the first year of treatment was uncommon with all three INSTIs (about 1 case per 100 patient-years of exposure). The lowest overall resistance rates were observed in those treated with dolutegravir (1.48 cases/100 patient-years) followed by elvitegravir (2.37) and raltegravir (3.80). Factors significantly associated with the development of drug resistance included being female, having a pre-INSTI HIV RNA level >100,000 copies and/or a CD4 count <200 cells/µL, and having <80% adherence to the INSTI regimen. Of the 27 cases of resistance identified, 14 occurred with raltegravir-based antiretroviral therapy (ART), 8 with elvitegravir-based ART, and 5 with dolutegravir-based ART. Only 4 of 27 resistance cases occurred in patients on their first ART regimen, 2 of whom developed emergent INSTI mutations, including 1 receiving dolutegravir.

Comment

These data from a real-world clinic-based cohort confirm the very low rate of emergent resistance occurring in patients who start integrase inhibitor–based ART for HIV infection and support the important role of INSTIs in the management of both treatment-naive and treatment-experienced HIV-infected patients. In the few patients who developed resistance, well-known resistance risk factors were most often implicated: poor adherence and advanced HIV disease.

Editor Disclosures at Time of Publication

  • Disclosures for Charles B. Hicks, MD at time of publication Consultant / Advisory board Gilead Sciences; ViiV; Merck Royalties UpToDate, Inc. Grant / Research support NIH; Department of Health and Human Services

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