How HIV Causes Premature Aging

Persistent Inflammation Linked to Increased Risk of Aging-Associated Illnesses

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HIV infection is characterized by long-term immune activation, wherein the body responds to the presence of the virus by producing defensive antibodies and pro-inflammatory proteins. The increased immune activation and persistent, chronic inflammation associated with HIV are considered major players in the aging process, resulting in premature frailty and aging-associated diseases.

This accelerated process is often referred to as premature senescence.

Defining Aging and Premature Aging

Premature senescence is defined as the biological aging of an individual or organism at a time much earlier than expected or experienced in the general population.

Roughly speaking, aging is characterized by the body's decreased ability to face stresses, making it more difficult to maintain biological stasis (equilibrium), while increasing the risk of aging-associated diseases like Alzheimer's or metabolic bone disorders. Premature senescence implies that the body is aging well before its time and can usually be linked to one or several causal agents or events.

Normal aging is associated with chronic, low-grade inflammation—known as inflammaging—which plays a role in the slowing of cellular growth, as well as the gradual loss of tissue function. The mechanics of aging are considered, by and large, inevitable, although genetic, environmental and age-related factors can determine an individual's vulnerability to aging and death.

By contrast, premature senescence is associated with chronic inflammation which is greater than that experienced in the average, healthy individual. This elevated level of persistent inflammation can cause accumulative damage on a cellular and molecular level, placing cells under an oxidative stress to where they are less able to detoxify the body or repair damage.

Inflammation can cause direct damage to genes to where the genetic coding of cells altogether changes—resulting often in cell death or the development of cancerous mutations. In time, the affected cells stop dividing altogether, and the body as a whole literally ages.

Premature senescence can be caused by certain infections, as well as behavioral factors such as smoking and obesity, or environmental factors such as pollutants or radiation.

Premature Senescence and HIV Infection

As people with HIV can now expect to live normal to near-normal life spans, given the timely initiation of ART, greater focus in being placed on many non-HIV-associated illnesses that can take back many of those gains. In fact, in most developed countries, diseases associated with immune suppression—so-called opportunistic infections—are no longer the foremost killers of people with HIV.

Instead, non-AIDS-related cancers are today considered the leading cause of death for HIV-infected people across North America and Europe, with most being diagnosed 10-15 years earlier than their non-infected counterparts.

Similarly, the neurocognitive impairment associated with aging are seen in people with HIV at a median age of 46, while the median age for myocardial infarctions (heart attacks) stands at a mere 49 years—seven to 16 years earlier than uninfected men or women.

Even when HIV is well-controlled by way of antiretroviral therapy (ART), HIV-infected people are still prone to the early onset of aging-associated illnesses, albeit at a significantly lower rate.

Patients with early ART and a high CD4 nadir are generally seen to be under lesser burden of chronic inflammation than those who start treatment late, while patients with sustained viral control are considered less vulnerable to age-related comorbidities than individuals who are either untreated or unable to achieve viral suppression.

Early diagnosis and treatment are, therefore, key to delaying the premature aging often noted in people with long-term HIV disease.


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