The curious case of accelerated aging with HIV

The phenomenon of accelerated aging in people living with HIV is the complex result of various biological, environmental and social factors; however, it is predominantly the body’s response to the chronic inflammation associated with HIV.

“I would say the most prominent or specific reason [for accelerated aging] is a chronic inflammation that can occur,” Monica Gandhi, MD, MPH, an infectious disease and HIV specialist at the University of California, San Francisco, and the medical director of the Ward 86 HIV Clinic, in San Francisco, told Infectious Disease Special Edition.

Based on previous studies that documented the effects of HIV on aging, Dr. Gandhi explained how her clinic justified a cutoff age of 50 years for people with HIV instead of a more traditional medical milestone age of 60 or 65 in people without HIV.

“We have given a lot of thought to this age cutoff of 50. What I mean by that is there are some studies that look at people who are 50 living with HIV, and if you consider their endovascular system, the kind of thickening [and aging] of their vessels, they look more like they’re 60,” Dr. Gandhi said.

A Constant Fight

Even with highly effective antiretroviral therapy (ART), the immune systems of people with HIV are continually battling the virus, and it begins to take a biological toll.

“That chronic inflammation can lead to thickening of the vessels—inflammation of the vessels that feed the heart, causing coronary artery disease or vessels that feed the liver or the kidneys,” Dr. Gandhi said. “That can lead to the inside of a body looking older in someone living with HIV by about 10 years more than someone without HIV.”

Dr. Gandhi additionally attributed some of this acceleration in aging to the consequences of older, less tolerated HIV medications that were used previously.

“I would say that definitely, things have absolutely improved in terms of the aging phenotype, and just in terms of living with HIV in general,” she said.

She used the example of ritonavir, a protease inhibitor—the same medication used right now against COVID-19 (nirmatrelvir/ritonavir [Paxlovid, Pfizer]).

“The high doses of protease inhibitors [used to treat HIV] could lead to weight gain, could lead to heart disease, actually could lead to higher rates of myocardial infarction,” she said.

Dr. Gandhi also noted the use of nucleotide reverse transcriptase inhibitors (NRTIs) like zidovudine (AZT), didanosine (DDI), stavudine (d4T) and dideoxycytidine (DDC) were particularly hard on a patient’s system, leading to various comorbidities in those with HIV.

“We also had some what are called NRTIs ‘nukes’—that were pretty hard to take early on like AZT, DDI, d4T and DDC. These were medications that accelerated aging, led to liver disease, led to weight changes, led sometimes to pancreatitis or neuropathy,” Dr. Gandhi added.

Even some of today’s more tolerable ART can increase lipids and cause weight gain and other issues that can lead to metabolic syndrome and other conditions. However, with the advancement of ART, there are opportunities to mitigate these trends, according to Dr. Gandhi.

“Remember, June 5, 1981 was the first CDC [report] of these terrible infections in young, mostly gay men, and that really marked the start of the HIV epidemic in the U.S. So, if you go forward, if people were diagnosed early on—early 1980s, even early 1990s—we’re seeing more of that accelerated phenotype than if they were diagnosed later but [now] they’re older,” she said (MMWR Morb Mortal Wkly Rep 1981;30[21]:1-3).

“I think we’re already seeing this trend, where the earlier [into the HIV/AIDS pandemic] you were diagnosed, the more likely you were to age [prematurely],” Dr. Gandhi noted. “Now we have better medications. We start everyone with HIV on medication right away; we don’t let them wait until their T-cells go down, which is what we used to do with the more toxic medications. So, we’re in a different phase with treating HIV more aggressively. We’re treating earlier; that’s keeping the inflammation down and hopefully leading to less aging.”

Preconceived Barriers to Treatment

As medications and therapy for HIV progress, there is still work to be done to overcome social and environmental barriers to accessing these improved drugs.

“In my view, the major concern from the patient side is all the stigma [associated with HIV] among society, among peers and relatives,” said Khairul A. Siddiqi, PhD, an assistant research scientist at the University of Florida College of Medicine, in Gainesville. Dr. Siddiqi served as first author on a recently published study evaluating health trends of people with HIV from 2003 to 2015 (HIV Med 2022:1-11. doi:10.1111/hiv.13325).

Dr. Siddiqi and his colleagues found increased rates of hospitalization and HIV-associated non-AIDS comorbidities among older people with HIV. As these people get older, they will place more of a burden on the healthcare system and require more medical and hospital resources, they said.

Better training for healthcare providers and physicians on managing an older person with HIV is crucial and should include care of comorbidities, such as cardiovascular disease.

“I was attending a conference a couple of months back, and an HIV patient was talking about these stigmas,” Dr. Siddiqi said. “His wife, his kids—nobody knows about his HIV status because he knows if he were to speak out, his life could be miserable. So, he keeps all his [ART] in a separate medication box in his car.”

Dr. Siddiqi added that the negative preconceived ideas held by some people, including some healthcare providers, can deter adherence to adequate HIV treatment. However, some of these barriers could begin to be addressed with additional funding and resources.

“The health department, the community health centers and other community-based organizations, and maybe the political organizations could work together to [educate] the [community] so that there is more openness and less miscommunication around [HIV]. But we need funding for that,” Dr. Siddiqi said.

A Golden Compass Instead of Gold Watch

Dr. Gandhi detailed what her clinic is doing to meet these challenges and successfully treat older people with HIV by describing her own clinic’s HIV treatment program.

“In San Francisco, we started an HIV and aging program in 2017, called Golden Compass, and we decided to provide extra services—extra medical care for those who are older [and living with HIV],” she said.

“We’re bringing in other doctors [to complement] our HIV doctor expertise. We’re bringing in [experts in] cardiology, pulmonology and geriatrics to help us have a comprehensive aging program.”

Dr. Gandhi also recognized how fortunate her clinic is to have the funding and resources to include cardiology, pulmonology and geriatrics in its program, but said lack of resources should not stop other primary care physicians from trying to incorporate some of these strategies into their own practices.

“Geriatric care has some very basic elements that we can all learn as primary care doctors,” she said, such as, “frailty assessments–making sure the home is safe, making sure that people are walking well, making sure there aren’t key abnormalities—things that would worry us about fall risk.”

She also said cardiology care, even basic preventive cardiology care, is an important part of any successful primary care practice. “So, think about lipid management, diabetes, smoking cessation, exercise and other lifestyle changes to help keep down that risk of cardiology problems.”

Slowing Down the Clock

This is increasingly becoming an area of study for HIV specialists, to understand this accelerated aging and to slow it down, according to Dr. Gandhi.

An example she gave is the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) study that is evaluating the use of pitavastatin to reduce the risk for cardiovascular disease in people with HIV.

“So, [the REPRIEVE study is] specifically for people who don’t need a statin to bring down their cholesterol but just the anti-inflammatory properties of a statin to help people with accelerated aging, and I think, it’s going to be really important for us to see if we should be giving a statin to everyone living with HIV,” Dr. Gandhi pointed out.

“I think that for those of us working in HIV, we’ve been worried about accelerated aging for a long time,” she said. “It’s only by bringing more awareness to the problem by talking about successful programs like the Golden Compass program at the Ward 86 HIV Clinic that other healthcare providers can emulate it and bring the best practices together, changing the course of some of these accelerated aging phenotypes.”

By Landon Gray