Aging With HIV: Managing Comorbidities in a Population That Has Outlived Its Prognosis

When antiretroviral therapy (ART) transformed HIV from a terminal diagnosis into a manageable chronic condition, it set in motion a demographic shift that medicine is still catching up to. More than half of the people living with HIV (PLWH) in the United States are now over the age of 50,¹ a milestone that would have been unimaginable in the early years of the epidemic, and that stands as one of the most consequential successes in modern infectious disease medicine. But longevity has arrived with a new clinical complexity, one that treatment guidelines, comorbidity algorithms, and specialty training pipelines were not designed to address. The patients who survived are now aging, and they are doing so in ways that differ meaningfully from the general population.

The concept of HIV-associated accelerated aging has moved from hypothesis to hard evidence over the past decade. Researchers have documented changes across virtually every cellular pathway implicated in the biology of aging, and these changes are not fully reversed by antiretroviral therapy.^2,3 They manifest clinically in elevated rates of cardiovascular disease, metabolic disorders, neurocognitive impairment, malignancy, frailty, and osteoporosis at ages and disease stages where the general population would not yet be considered high risk.^2,4 A 52-year-old person living with HIV on stable ART may have the physiologic and comorbidity profile of someone a decade older, but the standard clinical frameworks for managing that complexity—geriatric assessment, polypharmacy review, and cardiovascular risk stratification—have rarely been adapted for this population.

WATCH NOW>> From Pathogen to ID Diagnosis: HIV Drug Resistance Declines in the Modern ART Era

The gaps are consequential. HIV-associated neurocognitive disorder (HAND) affects an estimated 40% to 50% of people living with HIV across all age groups,⁵ yet screening in primary and ID care settings remains inconsistent, and the clinical boundary between HIV-related cognitive change and age-related decline has become increasingly difficult to draw. Cardiovascular disease remains the leading non-AIDS cause of death in this population, even among patients on suppressive therapy, and data from the REPRIEVE trial have already prompted changes to AHA statin guidelines specific to HIV.⁶ Polypharmacy—driven by the convergence of ART, cardiovascular medications, psychiatric medications, pain management, and more—creates drug-drug interaction profiles that clinicians in other specialties are often unprepared to navigate. And frailty, once considered a concern only for octogenarians, is now documented in people living with HIV in their 40s and 50s.⁷

Kristine M. Erlandson, MD, MS, is a professor of medicine at the University of Colorado School of Medicine, where her research has focused on physical function, frailty, and multimorbidity in older adults living with HIV. She has authored multiple studies on the mechanisms and clinical consequences of HIV-associated aging and is among the leading voices calling for the integration of geriatric frameworks into HIV care well before patients reach traditionally defined thresholds for aging-related assessment.

In the conversation that follows, conducted as part of Contagion's HIV Awareness Month series, Erlandson addresses the questions that ID clinicians are navigating in real time: when to apply a geriatric lens, how to screen for neurocognitive changes efficiently, how to interpret cardiovascular risk in a post-REPRIEVE world, and how to approach the drug interaction landscape in patients whose medication lists grow longer every year. Her answers offer both practical guidance and a broader argument—that the patients who outlived the prognosis of the early epidemic now deserve a clinical infrastructure built for the complexity of the lives they are living.

Transcript edited for clarity.

Contagion: At what age or clinical threshold should a physician start applying a geriatric framework to HIV care?

Kristine M. Erlandson, MD, MS: Often, we think about aging issues in people with HIV starting at about age 50, but this is definitely not applicable to all! Some aspects of the geriatric framework we can apply across the lifespan (preventive care, cancer screenings, healthy brain aging factors, and the importance of exercise and good nutrition). Other components may not be applicable for some of our patients until well after age 50.

Contagion: What does "accelerated aging" in HIV actually mean at the cellular level, and how does it manifest clinically?

Erlandson: We can think about accelerated aging and the cellular level by the “hallmarks or pillars” of aging. These are the age-associated drivers that underlie the development of many different comorbidities, and we believe that many of these hallmarks are impacted by HIV. For example, people with HIV may experience an acceleration in epigenetic age clocks (most apparent among those with HIV not on ART, but also to a lesser extent related to HIV on treatment).

We also see changes in mitochondrial function, metabolism, cell senescence, the microbiome, inflammation, proteomics, and many other pathways that contribute to aging-related conditions. Changes in mitochondrial function could manifest as fatigue, lower exercise endurance, among other changes. Cellular senescence could contribute to an increased risk for infections or a less effective response to vaccines. Combined, these pathways likely contribute to the more pronounced risk for cardiovascular disease, diabetes, some cancers, and other age-related conditions. 

Contagion: How should cardiovascular risk be assessed and managed differently in a patient on long-term ART vs. the general population?

Erlandson: We now know from REPRIEVE (as reflected in recent AHA guideline changes) that people with HIV have a decreased risk for cardiovascular disease events when taking a statin. As reflected in the guideline changes, we should counsel all patients aged 40 and older on the benefits of statin therapy, even when other risk factors wouldn’t indicate use in the general population. We also know the importance of aggressive blood pressure management, similar to the general population.

From REPRIEVE, we also know that people with HIV continue to have cardiovascular events even when on therapy—the ideal additional treatments for treating this “residual risk” are not yet known, but lifestyle modifications (healthy nutrition and exercise) are likely even more important in people aging with HIV and ART.

Contagion: HAND affects up to half of all PLWH—what should frontline ID clinicians be screening for, and when should they refer to neurology?

Erlandson: Disentangling HIV-related cognitive impairments from age- and comorbidity-associated impairments has become increasingly difficult. ID clinicians should focus on healthy brain aging for patients with HIV, including management of cardiovascular disease risk (statin, blood pressure management), substance use treatment, exercise and good nutrition, socialization and management of mood disorders, and treatment of other preventable contributors (such as hearing loss). Asking patients can be an easy first step! The EACS Guidelines recommend 3 simple questions: 

1. Do you have problems with memory loss?
2. Are you slower with reasoning/planning?
3. Do you have difficulties paying attention?

The Mini-Cog is another quick and simple test (3-word recall and drawing a clock face). Abnormalities on these tests might prompt a referral to neurology. Other abnormal exam findings or more rapid changes would also prompt a referral.

Contagion: Polypharmacy is a serious concern in this population; which drug-drug interactions between ART and common comorbidity medications should clinicians prioritize?

Erlandson: The boosting agents are the most problematic for drug-drug interactions (ritonavir and cobicistat) and the associated protease inhibitors. If these medications can be avoided, that is ideal for avoiding a drug-drug interaction, though certainly some patients require these for a more resistant virus. Steroids are probably one of the more problematic and commonly prescribed medications that are often prescribed by other providers. Some steroid nasal sprays, inhalers, and joint injections can be problematic and are often not considered when considering drug-drug interactions. There are often unexpected drug-drug interactions, so utilizing something like the Liverpool website before prescribing a new medication is always a good idea!

It is also important to note that many medications are considered more dangerous for older adults, even without drug interactions. The Deprescribing.org website has some helpful tools to help deprescribe some of these more problematic medications. 

REFERENCES

1. Centers for Disease Control and Prevention. HIV Surveillance Report, 2022; vol. 34. Published May 2024. Accessed June 2026. https://www.cdc.gov/hiv/library/reports/hiv-surveillance.html

2. Erlandson KM, Karris MY. HIV and aging: reconsidering the approach to management of comorbidities. Infect Dis Clin North Am. 2019;33(3):769-786. doi:10.1016/j.idc.2019.04.005

3. Bekele T, Platton S, Raboud J, et al. Epigenetic age acceleration and HIV: a systematic review and meta-analysis. Aging (Albany NY). 2023;15(4):1218-1237. doi:10.18632/aging.204536

4. Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011;53(11):1120-1126. doi:10.1093/cid/cir627

5. Saylor D, Dickens AM, Sacktor N, et al. HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment. Nat Rev Neurol. 2016;12(4):234-248. doi:10.1038/nrneurol.2016.27

6. Grund B, Carr A, Dongen MV, et al; REPRIEVE Investigators. Statin therapy to prevent cardiovascular disease in adults with HIV. N Engl J Med. 2023;389(14):1273-1283. doi:10.1056/NEJMoa2307888

7. Desquilbet L, Jacobson LP, Fried LP, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci. 2007;62(11):1279-1286. doi:10.1093/gerona/62.11.1279