A mathematical modelling study coordinated by UMC Utrecht has shown that sustained HIV remission (without rebound) or HIV eradication cure scenarios could consistently reduce new HIV infections among men who have sex with men (MSM) in the Netherlands as compared to a scenario without a cure.

The investigators anticipate that the introduction of either of these cure scenarios could contribute to ending the HIV epidemic among MSM in the Netherlands. In contrast, transient HIV remission with a risk of rebound could increase new infections if rebounds are not closely monitored, and could potentially undermine HIV control efforts.

Over the past decades, significant progress has been made toward achieving the United Nations Sustainable Development Goal of ending the HIV epidemic by 2030. Successes in reducing HIV transmission are particularly notable among men who have sex with men in several Western European countries, including the Netherlands.

Since 2008, the annual number of HIV diagnoses and HIV incidence among MSM in the Netherlands have declined by approximately 70%, largely due to public health interventions such as pre-exposure prophylaxis (PrEP) and the use of antiretroviral treatment (ART) to prevent sexual transmission of HIV. Despite these advances, the development of an HIV cure remains a global health priority, as millions of people worldwide depend on lifelong ART for viral suppression, and a preventive vaccine is not yet available.

People living with HIV, including those in key populations such as MSM, may experience impaired health-related quality of life despite—or in some cases due to—ART. Compared to individuals without HIV, people with HIV are more likely to be dealing with physical and mental health issues due to chronic comorbidities and stigma.

Acceptable and scalable HIV cure

Biomedical research and human clinical trials for curative HIV interventions are advancing rapidly. To date, several patients have been cured of HIV through HIV-resistant stem cell transplants, but a scalable cure has yet to be developed and may take considerable time to become widely available. The consensus is that an acceptable and scalable cure for HIV will most likely require a combination of strategies targeting different aspects of HIV infection.

HIV eradication—defined as the complete removal of HIV from the body—represents the ultimate goal for people with HIV. However, HIV remission—where the virus remains suppressed below transmissible levels without ongoing ART—could be a more attainable target for researchers. Strategies that are currently being developed may contribute to both HIV remission and HIV eradication.

Mathematical modeling

An interdisciplinary research group led by infectious disease modeller Rozhnova, Ph.D. (Research Program Infectious Diseases, Julius Centre for Health Sciences and Primary Care, UMC Utrecht) assessed whether an effective cure could help end the HIV epidemic.

Two cure scenarios were investigated: HIV remission, where the virus is suppressed in an individual without ongoing ART but may rebound, and HIV eradication, which aims to completely remove the virus from the individual. For this study, they developed a mathematical transmission model, calibrated to data from MSM in the Netherlands. The results of this study were published this week in Nature Communications.

Maximising cure benefits

The results showed that sustained HIV remission (without rebound) or HIV eradication could consistently reduce new HIV infections compared to a scenario without a cure. In contrast, transient HIV remission with a risk of rebound within a few years could increase new infections if rebounds are not closely monitored, potentially undermining HIV control efforts. Specifically, if the mean time to rebound in individuals who achieve HIV remission is two years, even monitoring as frequently as every two weeks would be insufficient to mitigate the increase in new infections.

If the mean time to rebound is six years, new HIV infections would decrease, but frequent rebound episodes would require ongoing efforts for rapid viral load monitoring and timely diagnosis of rebounds to maximise the public health benefits of any HIV remission strategy. These findings emphasise the critical role of cure characteristics in maximising cure benefits for public health and highlight the need to align HIV cure research with public health objectives to end the HIV epidemic.

Further research needed

Principal investigator Rozhnova concluded, "Our study—the first one to assess the potential impact of an HIV cure on the epidemic among MSM in a Western European country with a low HIV incidence and high ART coverage—suggests that both HIV eradication and sustained HIV remission have the potential to reduce new HIV infections in the Netherlands, contributing to the goal of ending the HIV epidemic. However, transient HIV remission could increase infections if rebounds are not promptly monitored."

This research is part of the modelling working group, co-led by Ganna Rozhnova, Ph.D., in the SPIRAL consortium (coordinated by virologist Monique Nijhuis, Ph.D,. from UMC Utrecht. The researchers are further adapting the model to explore how different cure characteristics will affect HIV transmission in other settings, including Africa.