HIV Patients Appear to Age More Rapidly; Researchers Want to Know Why That Is

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By Annette M. Boyle

WEST HAVEN, CT – The median age of the 24,000 veterans with HIV receiving care at the VA today is 53 — and many look and feel far older.

The loss of muscle mass in the arms and legs, hunched appearance and other signs of aging seem so much more pronounced among older patients with HIV that patients, caregivers and some researchers contend that the infection causes premature aging.

“When compared with behaviorally and demographically similar HIV-uninfected individuals, people with HIV infection, even those receiving effective ART [antiretroviral therapy] with suppression of virus to levels below typical detection limits, experience excess morbidity and mortality,” according to a recent report on HIV and Aging published in the Journal of Acquired Immune Deficiency Syndromes.1

“On average, a 20 year old initiating ART may have already lost one-third of the expected remaining years of life, compared with demographically similar HIV-uninfected persons,” according to the HIV and Aging Working Group that authored the report.

The authors include Amy Justice, MD, PhD, section chief, General Internal Medicine, of the VA Connecticut Healthcare System and professor of medicine at Yale University and Michael Shlipak, MD, MPH and Paul Volberding, MD, both of the San Francisco VA Medical Center and University of California, San Francisco.

 What Accelerates Aging?

How and why HIV patients appear to age more rapidly, though, is a subject of some debate.

Some suspect that the drugs used to control the virus may themselves contribute to aging and development of comorbidities.

“Early on in the battle against HIV, we used drugs with major toxicity. While they were effective, they had nasty side effects. Some of the big bellies, wasting in faces and ‘buffalo humps’ seen in older patients are at least in part due to those drugs, which we don’t use much anymore,” Justice told U.S. Medicine.

On the other hand, the Strategies for Management of Anti-Retroviral Therapy (SMART) “trial looked at whether people did better with treatment holidays or continuous treatment and found that, not only did HIV continue to progress during the breaks, the non-HIV conditions also worsened. We had thought some of those conditions were drug-related, but they appear to be associated with HIV itself,” said Justice.

The SMART trial followed patients on current treatment protocols.

Others attribute accelerated aging to an unchecked and ongoing inflammatory response triggered by the infection. According to Mark Holodniy, MD, FACP, director of the HIV clinical program and AIDS Research Center at VA Palo Alto Health Care System and professor of medicine at Stanford University in California, the increased damage from these factors can be seen in much higher numbers of biomarkers for inflammation, which are often indicative of disease.

Other researchers say they think the explanation is far simpler and that other descriptions of the process can be more helpful.

According to Justice, “it’s one thing to observe that these folks look older than their stated age and another to call it premature aging, which is a well-defined syndrome quite different from what people in the HIV world are talking about.”

“People think that anyone with HIV will feel 20 to 30 years older than their stated age, but the evidence doesn’t support that. They may look somewhat older, but if you compare anyone with a serious chronic disease to someone in the community in good health, you’ll see the same difference,” Justice said.

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Aging Cohort Study

To isolate the impact of HIV, Justice and her colleagues initiated the Veterans Aging Cohort Study (VACS). VACS comprises two cohorts: The first includes a virtual cohort of 40,000 HIV positive veterans from national VA data starting in 1997 and 80,000 HIV negative controls matched by age, race and site. The second is a prospectively consented cohort of 7,000 veterans currently in care at eight VAMCs in which HIV positive patients are matched by age, race and site to HIV negative patients.

“When we look at veterans with HIV and compare them to HIV negative patients also in VA care, we see a difference on the order of one to six years — not 20 or 30. People in care in the VA are not perfectly healthy individuals, with or without HIV. It’s important to understand why people feel old and tired, but we need to be careful not to overstate, not to scare the living daylights out of people,” said Justice.

To help veterans and others with HIV translate their lab results into a number that shows the impact of specific health indicators on longevity, Justice and her team developed the VACS Index Calculator, available online and in a mobile app. The VACS Index calculates the individual’s five-year mortality risk based on the data from the VACS study and provides a way for patients to see how changing certain metrics, whether through medical treatment or altered behavior, can extend their lives.

Eliminating a few unhealthy behaviors would have a huge impact on many older patients with HIV, noted Justice. “Smoking, using drugs, drinking definitely contribute to aging. And, increasingly, so does obesity, which increases risk for other diseases. It’s an interesting twist. Before starting antiretrovirals, many patients are quite thin. Then they start gaining weight rapidly. Should we take the approach we have for pregnant women, and say ‘It’s OK up to this amount, but not more?’”

Justice advises clinicians treating the growing number of older patients with HIV to think about the whole patient, as an individual. Whatever the cause, these patients are at greater risk for developing cancer, osteoporosis and cardiovascular diseases at younger ages and to have shorter expected life spans.

“It’s very important to tailor treatment to the individual. Don’t do every screening; think about the specific patient’s life expectancy.” The VA does not recommend performing a colonoscopy on a patient who is only expected live another seven to 10 years, for instance, because the test poses an immediate, if small, risk of perforation, while the patient is unlikely to live long enough to benefit from avoiding cancer.

For patients with HIV, “medication reconciliation is particularly important,” noted Justice, as most are already taking at least three drugs. “Not just for drug-drug interactions but for knowing the total number of medications. Studies show that if a patient is on more than five medications, the chance of an adverse effect goes up 10% for each medication. On 10 drugs, the chance is almost 100%.”

1. High KP, Brennan-Ing M, Clifford DB, et al. HIV and Aging: State of Knowledge and Areas of Critical need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group. JAIDS. 60:S1-S18, July 1, 2012.

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