HIV and Aging: Management Considerations

Advances in the potency and tolerability of antiretroviral treatment (ART) have resulted in people with HIV living longer. Life expectancy in individuals with HIV and on ART is comparable to those without HIV (71 vs 79 years of age, respectively).¹ According to the most recent data available from the CDC, there has been a gradual increase in the ages of individuals newly diagnosed and currently living with HIV. As of 2023, 42% of individuals with HIV are 55 years of age and older, with the highest group (26%) being in the range of 55 to 64 years of age.¹ A minority of these individuals had new diagnoses, with only 7% of new diagnoses occurring in older adults (55-64 years).¹ For these individuals with new diagnoses and older age, approximately one-third had AIDS at the time of HIV diagnoses (33.4% of those 55-64 years and 33.9% =65 years).¹

With older age, these individuals are experiencing comorbidities that are more commonly seen in older adults without HIV, including cardiovascular diseases, chronic kidney disease, and diabetes mellitus. Mortality rates have decreased significantly with the advent of ART, and now the major driver of mortality in these individuals is due to noninfectious complications and other comorbidities. In addition to the physical effects that occur with age, these individuals may also have more social demands/considerations including polypharmacy and drug–drug interactions.

Screening Recommendations

Recommendations for HIV screening include testing at least once in individuals aged 13 to 64 years and more frequently if they are at risk for HIV acquisition. Despite the number of older adults diagnosed with HIV annually, there is no standard recommendation for routine HIV testing in these individuals.² Testing is recommended as needed based on symptomatology and risk, which may result in delays in testing, as symptoms may be mistaken for those associated with aging and the possibility of HIV may not be on the forefront for the individual and healthcare provider.

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Treatment Recommendations

Current guidelines recommend initiating treatment in all individuals with HIV regardless of age and CD4+ count, as previous studies have demonstrated early initiation of ART results in lower rates of morbidity and mortality.² For older adults with HIV, initiation of ART as early as possible is even more critical, as complications from HIV are accelerated. Research has demonstrated that older adults may not have as robust of an immunologic response to ART, so earlier initiation is critical to minimize the effect of HIV on the nadir CD4+ count. In addition, older adults have an increased risk of developing not only HIV complications but other comorbidities commonly observed in older adults due to acceleration of these conditions that can be seen with chronic HIV. Initiation of ART in older adults with HIV has demonstrated significant reductions in the incidence of not only AIDS-related mortality but also non–AIDS-related mortality.

Current guidelines recommend use of an integrase strand inhibitor (INSTI) in combination with nucleoside transcriptase inhibitor (NRTI)–based regimens for initial treatment in most adults with HIV regardless of age.² For individuals who were receiving or have previously received long-acting cabotegravir (Apretude, ViiV Healthcare) for pre-exposure prophylaxis, the recommended initial treatment regimen is a protease inhibitor–based regimen if ART is initiated prior to availability of integrase resistance results. ² The current preferred regimens are shown in the Figure.

Selection of ART in older adults with HIV should include careful consideration of comorbidities and potential drug–drug interactions. There is a paucity of data with older adults receiving ART, specifically with respect to efficacy, safety, and pharmacokinetic data for a number of antiretroviral agents; however, a number of clinical trials have demonstrated similar efficacy and toxicity profiles for several agents currently recommended for initial treatment: bictegravir-emtricitabine-tenofovir alafenamide (BIC/FTC/TAF; Biktarvy, Gilead Sciences), long-acting cabotegravir-rilpivirine (LA-CAB/RPV; Cabenuva, ViiV Healthcare), and dolutegravir-lamivudine (DTG/3TC; Dovato, ViiV).^3-5

Maggiolo et al examined the efficacy and safety of ART switch to BIC/FTC/TAF in older adults 65 years of age and older with HIV. ³ Individuals were included if they were currently virologically suppressed (HIV-1 RNA <50 copies/mL) or on elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide or a tenofovir disoproxil fumarate (TDF)-based regimen. All individuals were followed through 96 weeks for both virologic and safety outcomes. Virologic suppression (HIV-1 RNA <50 copies/mL) was achieved in 94.2% and 74.4% of individuals at weeks 72 and 96, respectively. Many individuals were missing virologic data at both time points, likely due to the impact of the COVID-19 pandemic. For those who did not achieve virologic suppression at either time point, the virologic data were not available for evaluation. With regard to safety, there were no serious adverse events related to the treatment regimen. Three out of the 86 participants enrolled experienced treatment-related adverse events, which led to discontinuation of BIC/FTC/TAF. The results from this analysis demonstrated that despite the lack of virologic data, BIC/FTC/TAF is an effective and safe treatment regimen for older adults with HIV.

The efficacy and safety of a switch to DTG/3TC in older adults (age, =50 years) who were virologically suppressed was evaluated by Walmsley et al in a pooled analysis of the TANGO and SWITCH studies.⁴ Individuals were continued on their current ART (cART) or switched to DTG/3TC and evaluated through week 48. Of those older adults (n=364), virologic failure (HIV-1 RNA =50 copies/mL) was observed in less than 1% (1/177) and 2% (3/187) in the DTG/3TC and cART treatment arms, respectively, at week 48. CD4+ count was stable or increased in all individuals who switched to DTG/3TC regardless of age. Overall, a low number of serious adverse effects was reported in either treatment group; however, when compared across age groups, a higher incidence was seen in older adults. The results from this pooled analysis demonstrated that DTG/3TC had similar efficacy and safety regardless of age.

At CROI 2025, Calcagno et al presented results with use of LA-CAB/RPV for individuals 65 years of age and older.⁵ A total of 78 older adults with HIV who were initiated on LA-CAB/RPV were evaluated over a median of 17 months, at which time the majority (72) were still receiving LA-CAB/RPV. Virologic suppression was maintained (HIV-1 RNA <50 copies/mL) in all individuals with a median CD4+ count of 656 cells/mm³ at the end of the evaluation. The results corroborate data previously presented by Elliot et al that LA-CAB/RPV is safe and effective in adults, regardless of age.⁶

Treatment Considerations

When evaluating medication therapy in older adults with HIV, it’s essential to review their other medications for polypharmacy as well as potential drug–drug interactions. Individuals with HIV may also be taking other medications to manage comorbidities and often may use over-the-counter medications. Compared with older adults without HIV, polypharmacy is substantially more common among those in the same age groups with HIV. Polypharmacy is expected to increase with increasing age and duration of HIV, with data from the Swiss HIV Cohort Study demonstrating that rates of polypharmacy were 66% in those 75 years of age and older.⁷ The effects of polypharmacy can be significant, with increased risk for drug–drug interactions, increased toxicity or adverse events, and increased risk for medication errors.

Evaluation for potential drug–drug interactions is critical to ensure both efficacy and safety of ART. Assessment of these interactions must include not only prescription medications but over-the-counter medications, supplements, and herbal products. The HIV Drug Interactions checker via the University of Liverpool is an excellent resource for prescribers to use to identify any potential interactions.

Along with assessment of concurrent medications for polypharmacy and drug–drug interactions, evaluation of kidney function is necessary to ensure optimal dosing of ART and minimize potential toxicity. Although commonly utilized for assessment of renal function and drug dosing, the Cockcroft-Gault equation has been shown to not be as accurate in predicting renal clearance in older adults. Current guidelines recommend using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating renal clearance in individuals with HIV.⁸ Despite these guidelines and recommendations being published in 2014, a recent survey of HIV clinicians presented at IDWeek 2025 by Shulman et al demonstrated that only approximately one-third of respondents were using the CKD-EPI equation in practice and were relying on use of either the Modification of Diet in Renal Disease or Cockroft-Gault equation.⁹ The authors highlighted the need for targeted education and reinforcement of current guidelines for optimal assessment of renal clearance, which is especially critical in these older adults who may have impaired renal clearance.

Management of Common Comorbidities In the Aging Population

The risk for comorbidities increases with age regardless of HIV status. Older adults with HIV are at an even higher risk for certain conditions due to effects of the virus itself or potential toxicity from the medications themselves.

Cardiovascular disease is of particular concern in older adults with HIV, as data from several cohorts have demonstrated that adults with HIV have approximately a 1.5- to 2-fold higher risk for cardiovascular disease compared with HIV-negative adults.² The increased risk may be due to several different factors, including metabolic effects from the medications itself, inflammation and immune activation from the HIV virus, and traditional lifestyle risk factors. Lifestyle modifications can help, as well as optimization of ART to minimize toxicity. In addition, individuals with HIV 40 to 75 years of age with an atherosclerotic cardiovascular disease (ASCVD) risk of at least 5% to 20% should receive at least a moderate-intensity statin based on data from the REPRIEVE trial, demonstrating significantly lower incidence of major cardiovascular events in those on statin therapy.² For those individuals 40 to 75 years of age with an ASCVD risk less than 5%, the guideline panel favors initiation of at least moderate-intensity statin therapy based on consideration of HIV and non–HIV-related risk factors.²

In addition to cardiovascular risk, older adults are commonly at risk for osteoporosis and decreased bone mineral density. Data have demonstrated that in US adults with HIV older than 50 years, 6% to 11% of those had confirmed osteoporosis with 28% to 45% demonstrating decreased bone mineral density.¹⁰ A meta-analysis published in 2021 by Chang et al demonstrated that individuals with HIV had a significantly higher incidence of all fracture events (4.08%) compared with those without HIV (0.44%), with a relative risk for all fractures of 1.91 (P<0.001).10 Similar results were seen when looking specifically at fragility fractures with rates of 2.66% and 2.19% in those with HIV and without HIV, respectively. Relative risk of fragility fractures was 1.68 in those with HIV (P<0.001). Bone mineral density scores were lower in those with HIV compared with HIV-negative individuals. The results of the meta-analysis demonstrated that those with HIV had significantly higher rates of fractures compared with those without HIV.

Regarding the effects of ART on bone mineral density, regimens that contain TDF or a boosted protease inhibitor are associated with an increased risk for loss of bone mineral density compared with those containing other NRTIs or INSTI- based regimens. Based on the significant increased risk for fractures and demonstrated loss of bone mineral density in individuals with HIV, current guidelines recommend routine bone mineral density monitoring in those who were male at birth, those who were 50 years of age and older, and postmenopausal individuals. When selecting or evaluating ART in these individuals, use of regimens with TDF or protease inhibitor–based regimens should be avoided, when possible, to decrease the risk for toxicity on bone mineral density.²

Resources

With the increasing number of older adults living with HIV, the AIDS Institute has led an initiative creating a National HIV and Aging Awareness Day, which is observed on September 18 to bring awareness to the unique needs and continued challenges. Several resources focusing on HIV care in the aging population are available:

HIV.gov: Aging with HIV

https://www.hiv.gov/hiv-basics/living-well-with-hiv/taking-care-of-yourself/aging-with-hiv

HIVinfo.NIH.gov: HIV and Older People

https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-older-people

National Institute on Aging: HIV, AIDS, and Older Adults

https://www.nia.nih.gov/health/hiv-aids/hiv-aids-and-older-adults

Discussion

Individuals with HIV are living longer due to the medical advances with ART and are now experiencing common comorbidities that are observed in the aging population without HIV. Older adults who are at risk for HIV acquisition should receive HIV testing based on risk, regardless of age, with ART started as soon as possible after diagnosis, regardless of CD4+ count, as they may have a diminished immune response compared with younger individuals. When selecting an ART regimen in older adults, clinicians must consider their current comorbidities and other medications to optimize the efficacy and decrease the potential risk for complications.

References

1. Deeper look: HIV and aging. AIDSVu. Accessed December 8, 2025. aidsvu.org/resources/deeper-look/hiv-and-aging/
2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Department of Health and Human Services. Updated September 25, 2025. Accessed December 8, 2025. clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv
3. Maggiolo F, Rizzardini G, Molina J, et al. Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: results of a 96-week, phase 3b, open-label, switch trial in virologically suppressed people =65 years of age. HIV Med. 2023;24(1):27-36.
4. Walmsley S, Smith DE, Górgolas M, et al. Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged = 50 years: week 48 pooled results from the TANGO and SALSA studies. AIDS Res Ther. 2024;21(1):17.
5. Calcagno A, Cossu MV, Gardini S, et al. Long-acting cabotegravir and rilpivirine in older people with HIV in the GEPPO cohort. Presented at: CROI 2025; March 9-12, 2025; San Francisco, CA. Abstract 677.
6. Elliot E, Benn PD, Clark A, et al. Long-acting cabotegravir+rilpivirine in older adults: pooled phase 3 week 96. Presented at: AIDS 2022; July 29-August 2, 2022; Montreal, Quebec, Canada. Abstract 4516.
7. Livio F, Deutschmann E, Moffa G, et al. Analysis of inappropriate prescribing in elderly patients of the Swiss HIV Cohort Study reveals gender inequity. J Antimicrob Chemother. 2021;76(3):758-764.
8. Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(9):e96-e138.
9. Shulman R, Binkley A, Leonberg-Yoo A, et al. A needs assessment of HIV clinicians in the evaluation and initial management of kidney dysfunction among people living with HIV: results from a cross-sectional survey. Presented at: IDWeek 2025; October 19-22, 2025; Atlanta, GA. Abstract 220.
10. Chang CJ, Chan YL, Pramukti I, et al. People with HIV infection had lower bone mineral density and increased fracture risk: a meta-analysis. Arch Osteoporos. 2021;16(1):47.

About the author:

Amanda Binkley, PharmD, BCIDP, AAHIVP, is a clinical pharmacy specialist in infectious diseases, and the PGY-2 infectious diseases pharmacy residency program director in the Department of Pharmacy at Penn Presbyterian Medical Center, in Philadelphia, Pennsylvania. Dr. Binkley also is a member of the Infectious Disease Special Edition editorial advisory board.

Dr. Binkley reported no relevant financial disclosures.

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