US: Substantial decline seen in HIV drug resistance this century

HIV drug resistance declined substantially between 2004 and 2021 among people living with HIV in Rhode Island, researchers found. However, some people living with HIV still have two-class and three-class resistance, and 15% of participants were ineligible for available long-acting treatment in 2021.

About This Study

“Acquired Human Immunodeficiency Virus Type 1 Drug Resistance in Rhode Island, USA, 2004–2021” was published online on July 23, 2024, in Journal of Infectious Diseases. The lead author is Su Aung, M.D., M.P.H., of the Department of Medicine at the University of California-San Francisco.

Key Research Findings

A single clinic in Rhode Island cares for 80% of those living with HIV in that state, allowing the researchers to use HIV sequences from 914 people living with the virus to calculate how common acquired drug resistance mutations were between 2004 and 2021. Most participants were men (62%) and over half were white (55%), while 32% of participants were men who have sex with men.

In 2004, the virus in 77% of participants was resistant to at least one antiretroviral drug. By 2021, this percentage had declined to 49% of participants. Virus mutations dropped fastest after 2016, when integrase inhibitors became widely used.

By drug class, the greatest decline in HIV mutations was against reverse transcriptase inhibitors (from 65% to 32% of participants for nucleoside and from 53% to 43% of participants for non-nucleoside inhibitors), followed by protease inhibitors (from 28% to 7% of participants). A non-significant trend was also observed for integrase inhibitors (from 16% of participants in 2017 to 13% of participants in 2021).

Resistance against more than one class of medications also declined, leaving most participants with at least one once-a-day pill option. One participant (who had acquired HIV perinatally) had no single daily pill option left, and six other participants had exhausted all their three-drug or two-drug single-pill options.

For 15% of participants in 2021, resistance mutations precluded them from using cabotegravir-rilpivirine as long-term injectable HIV treatment, which had just been approved in the U.S.

Discussion Highlights and Implications for Practice

Study limitations reported included reliance on possibly incomplete clinical data, lack of information on social determinants of health or treatment adherence, and non-transferability of results to geographic areas with different sociodemographic characteristics.

The authors believe that the decline in resistance mutations may be related to newer drugs that are better tolerated and easier to take, as well as less likely to confer resistance even when treatment adherence is imperfect. While this downward trend is encouraging, the potential for integrase inhibitor resistance needs to be monitored as people living with HIV age and are exposed to more antiretroviral medications, authors said.

By Barbara Jungwirth