Large fall in severe illnesses over two decades in Spain, while co-morbidities stay stable

Research from an 18-year Spanish cohort presented to the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco last week showed a significant reduction in severe non-AIDS events – such as heart attacks and non-AIDS cancers – over time. Other outcomes, such as hypertension and dementia, remained relatively stable over time in this cohort, with no significant increases.

Dr Alejandro Garcia, from the Hospital Ramón y Cajal in Madrid, presented these results.

As the number of older people with HIV has steadily increased over time, due to widespread availability of antiretroviral therapy (ART), there is an increased risk of multiple non-AIDS illnesses developing that are related to ageing. Cohorts such as CoRIS provide researchers with an opportunity to investigate these changes over time.

The study

The CoRIS study has been following people with HIV since 2006, with three main time periods compared by researchers: 2006-2011, 2012-2017 and 2018-2023.

The primary outcome of interest was severe non-AIDS events. This is divided into major cardiovascular events, such as heart attacks and stroke, non-AIDS cancers, such as lung cancer, and a third category to account for other types of deaths not related to AIDS – non-accidental, non-AIDS deaths.

Additionally, the researchers looked at seven secondary outcomes, including high blood pressure, type 2 diabetes, chronic kidney disease, bone fractures and dementia. They were also concerned with the total burden of illnesses (co-morbidity burden) and additional medications that people take as they age, or what the researchers termed polypharmacy burden. As researchers were only interested in incident or new events, they excluded people who had already had the outcome of interest, such as type 2 diabetes, at baseline.

A total of 18,659 participants who were not on ART at the time they entered the cohort were included in the analysis. The median age was 35. Most participants were male (80%); the number of gay and bisexual men increased over time, from 58% to 70%, while the number of injecting drug users sharply fell from 10% to 2%.

Decrease in significant non-AIDS events over time

In terms of the primary outcome, the prevalence of severe non-AIDS events decreased from 3.4% in the first wave to 2.6% in the second period and 2.1% for the 2018-2023 period. However, the prevalence of secondary outcomes remained stable over time.

The incidence of severe non-AIDS events most sharply declined among people aged over 50. There were also different trends for men and women, with women showing an initial increase in the incidence of these events and then a decrease, while men saw a larger, steadier decrease over time. While the 2012-2017 period was not significantly different to the 2006-2011 period, the 2018-2023 period showed a significant decrease in these events compared to the first period, with a 32% decrease over time (Adjusted Hazard Ratio: 0.68, 95% Confidence Interval: 0.50-0.92).

The incidence of all three events included in the primary outcome decreased over time: major adverse cardiovascular events, non-AIDS cancers, non-accident deaths and deaths overall. They occurred at older ages: the average age at which the first event occurred increased over time, from around 42 to 49 years old.

For secondary events, women saw an increase and then stabilisation over time, while men tended to display a more stable, slightly decreasing pattern over time. However, none of the later periods were significantly different from the first period, indicating a relative stability in secondary outcomes over time. For some secondary outcomes, such as chronic kidney disease, there does appear to be an upward trend in incidence as people with HIV age.

Across time periods, there was an increase in the number of co-morbidities as people aged. For instance, for people aged between 50 and 65, around half would have had no co-morbidities from 2006-2011, while around only 30% would have no co-morbidities in the last period. However, these differences were not statistically significant.

Additionally, the number of medications taken also rose with age. Thus, the finding that there was stability in the incidence of secondary events over time is an encouraging one: while there are more medications available to treat illnesses, there wasn’t a larger difference in the comorbidity burden when comparing periods.  

Conclusion

“We found significant reductions in the incidence of severe non-AIDS events and a delayed onset of these conditions in recent periods,” Garcia concluded. “There were no differences in the incidence of secondary events. Polypharmacy rose progressively, but the comorbidity burden didn’t change throughout the study.”

Dr Garcia noted that high numbers of people were on ART throughout the time periods – over 90% in the first two periods, and over 95% in the final period – indicating the centrality of ART use and adherence for overall health outcomes in people with HIV.