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HIV and Aging in the Era of Antiretroviral Therapy: Considerations in Clinical Care

Contagion, Contagion, October 2022 (Vol. 07, No. 5), Volume 7, Issue 5

With the population of adults with HIV growing older, incorporating age-based screenings, comprehensive assessments, and morbidity management into routine HIV care is essential in improving health outcomes and quality of life.

During the early years of the HIV epidemic, AIDS-defining illnesses significantly affected the clinical course and quality of life of the patient. Since the availability of effective and safer antiretroviral therapy (ART) in 1996, people living with HIV (PLWH) have life expectancies comparable to those of the general population in both high-income and low- to middle-income countries.1-4

However, chronic HIV infection and replication in anatomical reservoirs have been associated with immunosenescence, driven by chronic immune activation, chronic inflammation, and microbial translocation processes.1,2,4 This translates to a heightened risk of malignancy, infection, morbidity, and mortality.1 Thus, HIV infection and comorbid illnesses continue to present barriers to successful aging among people aging with HIV (PAWH).

According to the Centers for Disease Control and Prevention, the proportion of PLWH 50 years or older increased by over 100% from 2001 to 2014, with over half of HIV-infected persons now past the age of 50 years.5 To comprehensively assess and address the geriatric principles and issues that impact PAWH, the 5 Ms can be used: mind, mobility, multicomplexity, medications, and matters most.2,6


Evaluating cognition, mental health, and substance use is vital to decreasing risk for neurocognitive impairment, namely dementia and HIV-associated neurocognitive disorder (HAND).1,2,7 Chronic neuroinflammation has been shown to contribute to acceleration of neurocognitive aging, as evidenced by greater decreases in executive function and global cognition.8 HIV infection is also associated with greater cerebral white matter damage on magnetic resonance imaging (MRI) over time, despite effective treatment response to ART and no significant cerebrovascular risk factors.8

In PAWH, abnormal patterns of neurocognitive aging have also been found in HIV-positive individuals with a higher prevalence of depressive symptoms, with the limitation of most studies excluding participants with severe forms of psychiatric distress.7 Depression is associated with HIV-positive status and lifestyle factors, mainly substance use, and contributes to higher levels of emotional distress, social isolation, loneliness, and HIV-related stigma in PAWH.2,9

Stressors such as discrimination, poverty, unemployment, and social isolation are disproportionately seen in the HIV-positive population and are associated with poor health outcomes, depression, and anxiety.9 As a result, mood disorders, substance use, and cognitive decline should be evaluated with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, International HIV Dementia Scale, Montreal Cognitive Assessment, Alcohol Use Disorders Identification Test, or other screening tools as a part of routine care.2,9


Assessing frailty and physical function to identify vulnerable older adults with HIV is vital to developing multifactorial interventions to preserve and optimize mobility. Frailty is commonly measured in vulnerable older adults and can be viewed in 2 conceptual ways: the phenotype model and the cumulative deficit model. The phenotype model views frailty as a clinical syndrome composed of chronic undernutrition, sarcopenia, and weakened strength and exercise tolerance, whereas the cumulative deficit model views frailty as a state of vulnerability.1,9-11 Both refer to age-related deterioration marked by diminished physiological reserve and fragility to stressors that can be measured by frailty scales, such as the Fried frailty phenotype.9,10,12

In addition to the frailty scale, falls risk assessment and self-report of difficulty with activities of daily living and instrumental activities of daily living provide insight into the degree of disability.6 The Short Physical Performance Battery is an objective measurement tool for lower extremity function that has been validated to predict level of disability, need for nursing home placement, and mortality in persons 65 years and older.6 Measurement of physical function can be evaluated through assessments such as the Get Up and Go Test, gait speed, and Functional Reach Test. These measures also serve as strong predictors of mobility, disability, cardiovascular health, and mortality.12


In the era of antiretroviral therapies (ART) with high rates of viral suppression and low rates of toxicity, non–AIDS-defining illnesses and age-related comorbidities are becoming the leading cause of mortality in PAWH. These comorbidities include, but are not limited to, cardiovascular disease, hypertension, diabetes, osteopenia/ osteoporosis, cancer, neurocognitive impairment, and kidney and liver diseases.1,2,6,13,14

Cardiovascular disease consistently remains the leading cause of morbidity and mortality in PLWH, with a nearly 2-fold increased incidence of cardiovascular events compared with the general population. However, the use of aspirin, statin prescriptions, and antihypertensive drugs is significantly lower among PLWH.1,15 PLWH have the traditional risk factors, such as smoking, hypertension, obesity, and diabetes, along with HIV-related chronic inflammation, immune activation, and cardiometabolic dysfunction associated with the use of certain ARTs such as protease inhibitors.1 These factors all contribute to a prothrombotic state and vascular dysfunction.16

Unfortunately, conventional stratification models such as the atherosclerotic cardiovascular disease risk score and Framingham risk score do not consider these nonconventional risks factors that affect PLWH and thus underestimate risk in PLWH.16 Statin medications show benefit for both primary and secondary prevention through decreasing lipid abnormalities and limiting vascular and myocardial inflammation.1,16

HIV infection was shown to be independently associated with low bone mineral density, making PLWH almost 4 times more likely to have osteoporosis and higher rates of fracture.1,2 Thus, bone density screening at least once is recommended for postmenopausal women and men over the age of 50, yet screening rates remain low.2

Chronic liver disease serves as a major cause of morbidity and mortality for PLWH.2,13 Rates of coinfection with hepatitis B and C viruses are approximately 25 times higher than those of the general population, with increased rates of cirrhosis and hepatocellular carcinoma due to acceleration of liver fibrosis.1 Nonalcoholic fatty liver disease has been reported in 30% to 65% of PLWH and is the most common form of liver disease in this population.17

Although the prevalence of HIV-associated nephropathy has declined in the era of ART, the overall rates of acute kidney disease and chronic kidney disease have remained unchanged.14 Exposure to drugs with nephrotoxic potential such as tenofovir, and other comorbidities such as hypertension and diabetes, increase the risk for kidney disease.1,14

Although the prevalence of AIDS-defining malignancy has subsided over time with ART, PLWH have an elevated incidence of non-AIDS related cancers, as evidenced by increased rates of human papillomavirus–associated cancers such as cervical cancer in women and anal cancer in both men and women.1,13 Furthermore, staying up to date on screenings including screening for lung cancer for high-risk patients is strongly recommended.1 Among vaccine recommendations are those recommended for the immunocompromised population, including varicella and measles mumps, and rubella if CD4 count is 200 cells/μL or higher.2


PLWH have a higher use of antibiotics, analgesics, gastrointestinal drugs, central nervous system agents, and respiratory drugs than the general population.18 But with increased risk for comorbid illnesses, PAWH use more medications in total and more non-ART medications compared with older people living without HIV.19 Unfortunately, polypharmacy and multimorbidity are also associated with lower adherence to ART and other medications, potentially leading to worse health outcomes.6,18,19

Thus, evaluating medication safety and appropriate use is essential to decreasing potential concerns associated with polypharmacy. Potential problems include drug-drug interactions, adverse drug effects, increased pill burden, nonadherence, rising health care costs, and increasing risk of geriatric syndromes, specifically falls, fractures, and dementia.18


Along with the effects of chronological age, other factors and personal priorities of patients, such as lifestyle habits, substance use, sexual and social health, safety, sensory function (vision and hearing), nutrition, and health care utilization, should be incorporated into the care of PLWH.1,2,6 Because HIV disproportionately affects economically and socially disadvantaged groups, the health disparities widen with age and pose additional barriers to successful aging.

The body of evidence that demonstrates the increased burden of comorbidities in a population of people aging with HIV continues to grow. Therefore, integrating geriatric principles into routine HIV care is a highly multidisciplinary and resource-intensive process, but it is essential for optimizing health outcomes and quality of life for the aging population with HIV.


1. Escota GV, O’Halloran JA, Powderly WG, Presti RM. Understanding mechanisms to promote successful aging in persons living with HIV. Int J Infect Dis. 2018;66:56-64. doi:10.1016/j.ijid.2017.11.010

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. Teeraananchai S, Kerr SJ, Amin J, Ruxrungtham K, Law MG. Life expectancy of HIV-positive people after starting combination antiretroviral therapy: a meta-analysis. HIV Med. 2017;18(4):256-266. doi:10.1111/hiv.12421

4. Martínez-Sanz J, Serrano-Villar S, Vivancos MJ, Rubio R, Moreno S; HIV-associated comorbidities Study Group. Management of comorbidities in treated HIV infection: a long way to go. Int J Antimicrob Agents. 2022;59(1):106493. doi:10.1016/j.ijantimicag.2021.106493

5. HIV by age: HIV incidence. Centers for Disease Control and Prevention. Updated April 7, 2022. Accessed August 14, 2022. https://www.cdc.gov/hiv/group/age/incidence.html

6. Guaraldi G, Palella FJ Jr. Clinical implications of aging with HIV infection: perspectives and the future medical care agenda. AIDS. 2017;31(suppl 2):S129-S135. doi:10.1097/QAD.0000000000001478

7. Aung HL, Aghvinian M, Gouse H, et al. Is there any evidence of premature, accentuated and accelerated aging effects on neurocognition in people living with HIV? a systematic review. AIDS Behav. 2021;25(3):917-960. doi:10.1007/s10461-020-03053-3

8. Haynes BI, Pitkanen M, Kulasegaram R, et al. HIV: ageing, cognition and neuroimaging at 4-year follow-up. HIV Med. 2018;19(6):376-385. doi:10.1111/hiv.12598

9. Langebeek N, Kooij KW, Wit FW, et al; AGEhIV Cohort Study Group. Impact of comorbidity and ageing on health-related quality of life in HIV-positive and HIV-negative individuals. AIDS. 2017;31(10):1471-1481. doi:10.1097/QAD.0000000000001511

10. Brothers TD, Kirkland S, Guaraldi G, et al. Frailty in people aging with human immunodeficiency virus (HIV) infection. J Infect Dis. 2014;210(8):1170-1179. doi:10.1093/infdis/jiu258

11. Piggott DA, Erlandson KM, Yarasheski KE. Frailty in HIV: epidemiology, biology, measurement, interventions, and research needs. Curr HIV/AIDS Rep. 2016;13(6):340-348. doi:10.1007/s11904-016-0334-8

12. Greene M, Justice AC, Covinsky KE. Assessment of geriatric syndromes and physical function in people living with HIV. Virulence. 2017;8(5):586-598. doi:10.1080/21505594.2016.1245269

13. Proulx J, Ghaly M, Park IW, Borgmann K. HIV-1-mediated acceleration of oncovirus-related non-AIDS-defining cancers. Biomedicines. 2022;10(4):768. doi:10.3390/biomedicines10040768

14. Campos P, Ortiz A, Soto K. HIV and kidney diseases: 35 years of history and consequences. Clin Kidney J. 2016;9(6):772-781. doi:10.1093/ckj/sfw104

15. Okeke NL, Chin T, Clement M, Chow SC, Hicks CB. Coronary artery disease risk reduction in HIV-infected persons: a comparative analysis. AIDS Care. 2016;28(4):475-482. doi:10.1080/09540121.2015.1099602

16. Pyarali F, Iordanov R, Ebner B, et al. Cardiovascular disease and prevention among people living with HIV in South Florida. Medicine (Baltimore). 2021;100(28):e26631. doi:10.1097/MD.0000000000026631

17. Seth A, Sherman KE. Fatty liver disease in persons with HIV infection. Top Antivir Med. 2019;27(2):75-82.

18. Gimeno-Gracia M, Crusells-Canales MJ, Armesto-Gómez FJ, Compaired-Turlán V, Rabanaque-Hernández MJ. Polypharmacy in older adults with human immunodeficiency virus infection compared with the general population. Clin Interv Aging. 2016;11:1149-1157. doi:10.2147/CIA.S108072

19. Kong AM, Pozen A, Anastos K, Kelvin EA, Nash D. Non-HIV comorbid conditions and polypharmacy among people living with HIV age 65 or older compared with HIV-negative individuals age 65 or older in the United States: a retrospective claims-based analysis. AIDS Patient Care STDS. 2019;33(3):93-103. doi:10.1089/apc.2018.0190