Dolutegravir resistance is uncommon, but key factors increase risk, multinational analysis determines

While dolutegravir (DTG) resistance mutations are still rare, they are more common among people living with HIV (PLWH) who have a non-B subtype, as well as people on two-drug therapy and those with NRTI resistance, according to the results of a global analysis. As DTG continues to roll out globally, resistance needs to be monitored on a population level to ensure that it remains uncommon, the study authors urge.

About This Study

“HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis” was published online on Oct. 10, 2023, in The Lancet HIV. The lead author is Tom Loosli, M.Sc., of the Department of Infectious Diseases and Hospital Epidemiology at University Hospital Zurich, and of the Institute of Medical Virology at the University of Zurich, Switzerland. The related commentary “INSTI era resistance: emerging concern or marginal issue?” by Rami Kantor, M.D., of the Division of Infectious Diseases in the Department of Medicine at Alpert Medical School of Brown University in Providence, Rhode Island, was published in the same issue.

Key Research Findings

The study, called DTG RESIST, investigated DTG drug resistance among people living with HIV in Canada, Europe, and sub-Saharan Africa from 2013 to 2021. The 599 participants were viremic on DTG-based regimens and had genotypic resistance testing data. Sixty-nine percent of participants were men, 59% of participants had HIV subtype B (which is common in Europe and North America), 32% of participants had taken early INSTIs, and 85% of participants were on a triple-drug regimen.

Six percent of participants had DTG resistance and 14% of participants had INSTI resistance. DTG resistance mutations were more common in participants with resistance to nucleoside reverse transcriptase inhibitors (NRTIs), as well as those on DTG monotherapy or dual therapy with lamivudine, and participants with HIV subtypes other than subtype B.

Discussion Highlights and Implications for Practice

Reported study limitations included a lack of information on treatment adherence or the use of rifampicin for tuberculosis, the preponderance of participants with HIV subtype B, and the relatively short duration of DTG treatment.

The researchers remarked that while DTG resistance is currently rare, the risk factors for developing it could lead to transmitted mutations, especially in resource-limited settings.

Don’t lose sight of the benefits of DTG, the associated commentary urged. DTG-based regimens are “now globally accessible to almost anyone who needs it, saving people’s lives in all settings, circumstances, and vulnerabilities.” However, as that drug is rolled out globally, potential resistance needs to be monitored both on the individual and population levels. Ongoing research is investigating viremia while on DTG across the world.

By Barbara Jungwirth