Researchers at UMC Utrecht and their South African partners have developed a strategy to better determine who needs a resistance test when HIV treatment is not working effectively. The approach, developed as part of the ITREMA studies and led by virologists Anne Wensing (UMC Utrecht) and Kim Steegen (National Health Laboratory Service), both of whom are also affiliated with the University of the Witwatersrand in Johannesburg, has now been implemented in South Africa’s public healthcare system.
More than 40 million people worldwide are living with HIV. Integrase inhibitors are a key pillar of HIV treatment. Dolutegravir is widely used, particularly in low- and middle-income countries. When the viral load in the blood rises during treatment, it is important to determine whether the virus has become resistant or whether the medication has not been taken as prescribed. In practice, making that distinction is not easy. Furthermore, resistance testing is limited and relatively expensive, particularly in low- and middle-income countries.
The study, published this week in The Lancet HIV, investigated whether dolutegravir can be measured in the same blood sample already used to determine the amount of HIV in the blood. If no dolutegravir is detectable, integrase inhibitor resistance is highly unlikely. If dolutegravir is detectable while the virus continues to replicate, resistance testing can be used in a targeted manner. A total of 288 people living with HIV at two large public HIV clinics in Johannesburg participated in the study. When dolutegravir was not detectable, integrase inhibitor resistance could be ruled out with a negative predictive value of nearly 98 percent.
Anne Wensing, MD PhD
“An elevated viral load does not automatically mean that the treatment is no longer working due to resistance,” says Anne Wensing, MD PhD, principal investigator at UMC Utrecht. “By also measuring whether dolutegravir is present in the same blood sample, we can much more accurately determine who needs a resistance test. At the same time, the results provide doctors and nurses with objective information to offer more targeted support regarding medication adherence.”
Virologists, internists, pharmacists, clinical chemists, and researchers in the fields of health economics and implementation from the Netherlands and South Africa collaborated on a single care strategy. As a result, they examined not only the reliability of the test but also its integration into existing clinical and laboratory processes, its use in patient care, and the costs of large-scale implementation.
When the strategy is applied in the care pathway for confirmed virological treatment failure, the estimated monitoring costs per patient are 23 percent lower than with the current approach. Doctors and nurses also indicated that the results helped them to discuss medication adherence in a more targeted manner and prevent unnecessary changes in treatment.
A modified version of the reflex strategy has since been implemented by the South African Department of Health in public HIV care. With this, the approach has made the transition from research to routine clinical practice.
The ITREMA-2 study was funded by the Amsterdam Dinner Foundation through Aidsfonds and the Netherlands Organization for Scientific Research (NWO). It builds on earlier ITREMA research, supported by ZonMw and WOTRO, which was awarded a “Parel” by ZonMw.
Steegen K, Nel J, Smeijsters E, Umunnakwe CN, Mophiring K, Currin S, Tiel Groenestege WM, van Luin M, Hermans LE, Tempelman HA, Hans L, Jamieson L, Gumede S, Nyatela A, Venter WDF, Nijjhuis M, Wensing AMJ. Plasma dolutegravir exposure testing to identify people with HIV at highest risk for dolutegravir resistance (ITREMA-2): a two-centre, prospective implementation study in South Africa. The Lancet HIV, September 2, 2026
