The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.
But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.
“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.
Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.
“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.
“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.
Lampiris, who moderated the session where Althoff presented her findings, commented on it in an interview, but was not involved in her research.
Pathways to Comorbidity
The three primary pathways to comorbidities in people with HIV infections are as follows, according to Athloff:
The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
Individual risk factors, including smoking, stress, diet, exercise, and environment.
Cardiovascular and Renal Complications
Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Althoff said.
Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.
Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.
“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Althoff said.
Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.
Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.
“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
HIV has been linked to neurocognitive decline since the beginning of the epidemic, Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.
“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.
She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.
“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.
In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).
Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.
In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A1C levels, as well as neurocognitive impairment.
“Hemoglobin A1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Althoff said.
Reduce “Healthspan” Disparities
The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.
The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.
“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.
Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.
For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).
Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Althoff concluded.
Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.
“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”
Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Lampiris reported having no disclosures.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.