The widespread use of antiretroviral therapy (ART) has profoundly changed the natural history of human immunodeficiency virus (HIV) infection. People living with HIV now have a near-average life expectancy, which has led to a progressive aging of this population. As a result, age-related comorbidities have become a central clinical concern, often surpassing acquired immunodeficiency syndrome (AIDS)-related conditions in terms of morbidity and impact on quality of life. Cardiovascular disease, metabolic disorders, chronic kidney disease, fractures, neurocognitive impairment, malignancies, and polypharmacy are increasingly common among people with HIV and frequently occur at younger ages than in the general population.
The mechanisms underlying these trends are multifactorial and reflect a complex interaction between host factors and long-term HIV-related processes. Persistent immune activation and low-grade inflammation, even in virologically suppressed individuals, contribute to accelerated aging and organ damage. In addition, traditional risk factors, cumulative ART exposure, and social determinants of health further shape comorbidity risk. Sex-based differences are particularly relevant, as female with HIV tend to show a higher burden of certain comorbidities and a steeper increase in polypharmacy, likely influenced by biological factors as well as disparities in access to care and representation in clinical studies.
Recent longitudinal data suggest encouraging improvements, with a decline in the incidence of serious non-AIDS events and a delay in their age of onset over time. These trends likely reflect earlier ART initiation, better management of cardiovascular risk factors, and more proactive screening and prevention strategies. Nevertheless, the overall burden of chronic disease remains substantial, and polypharmacy has increased steadily, raising concerns about drug–drug interactions, adherence, and functional decline. These findings highlight the need to move beyond a purely HIV-focused approach and adopt integrated models of care that address multimorbidity, aging, and long-term wellbeing. Tailored strategies, particularly for female and other vulnerable groups, will be essential to optimize outcomes as the population with HIV continues to age.
Reference
Martínez-Sanz J, García-Ruiz de Morales AG, Macías J, et al. Trends in age-related health outcomes in people with HIV in Spain, 2006-2023. Clinical Infectious Diseases, 2025
