Since the start of antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV) infection, the life expectancy and quality of life of HIV-positive individuals have improved dramatically. With proper intervention and lifestyle changes, HIV-infected individuals are experiencing life spans closer to that of the general population.1 However, recent studies found that people infected with HIV were developing age-related diseases such as cardiovascular disease, kidney disease, liver disease, diabetes, cognitive decline, and osteoporosis at a higher rate and at an earlier age than people not infected with HIV.2,3 These findings suggest that HIV-positive individuals experience a faster aging process than people without HIV.

To investigate the possible link between HIV infection and accelerated aging, scientists at UCLA measured the DNA methylation levels in blood and brain tissue of HIV positive individuals and compared them to DNA methylation levels in blood and brain tissue of HIV negative individuals. DNA methylation is a molecular marker that changes in response to external stimuli and can affect how genes are expressed in the body. Changes in DNA methylation levels have been shown to correlate to accelerated aging effects.

What the UCLA scientists found after looking at DNA methylation supported the observations that HIV-positive individuals age faster. The scientists observed that the measured ages of blood and brain tissue from HIV infected individuals were on average 5.2 and 7.4 years older than the blood and brain tissue of non-HIV infected individuals, respectively. Interestingly, they found that only certain parts of the brain, specifically the cerebellum, which regulates motor movements, and occipital cortex, which is in charge of visual processing, exhibited accelerated aging effects. Additional studies need to be done to understand why only certain parts of the brain exhibited accelerated aging.

The scientists were also interested in looking at the relationship between accelerated aging, HIV virus levels, and peripheral blood mononuclear cell (PBMC) levels in the body. First, the scientists noted that HIV-infected individuals with a detectable amount of HIV virus in their bodies had an average DNA methylation age that was 3.6 years greater than those without a detectable virus level. However, it was not clear if these individuals with detectable virus levels were regularly taking their medications. Because the results were only marginally significant and the scientists were unclear about the individuals’ compliance towards their medication, more studies need to be done before any conclusions can be made regarding the association between HIV virus levels and epigenetic age.

The scientists then examined PBMC content in HIV-positive individuals. They noted a positive correlation between accelerated age and elevated levels of PBMCs. PBMCs, which are comprised mainly of T cells, B cells, NK cells, and monocytes, play an important role in our body’s immune system. When an individual is healthy, PBMC cells circulate in the body in a quiescent stage. When the body experiences an infection, PBMC cells become activated and differentiate into cells with different functions to defend the body.4,5 This effect was not observed in HIV-negative individuals, which suggests a correlation between accelerated age and PBMC content.

In this study, scientists showed that HIV-infected individuals had older brain and blood tissue when compared with their counterparts not infected with HIV. Based on their findings, the scientists theorized that HIV infection independently caused increased levels of immune cells and accelerated aging. This study had some limitations, such as limited sample size and limited knowledge regarding medication compliance. While the scientists showed that they were able to measure accelerated aging at a molecular level for HIV-infected individuals, additional studies need to be done to show how HIV infection leads to epigenetic age acceleration.

According to the Center for Disease Control and prevention (CDC), nearly half of those with HIV disease in the United States are now 50 years or older. As an increasing number of studies suggest that people with HIV are more likely to develop age-related diseases at an earlier age, it is important to take the appropriate measures to minimize these risk factors. This includes adhering to medication, minimizing behaviors such as smoking or drinking, and maintaining a healthy and balanced lifestyle.

Trickey A, May MT, Vehreschild, JJ, et al. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017; 4(8). 

Schouten J, Wit FW, Stolte IG, et al. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study. Clin Infect Dis. 2014; 59(12):1787-97.

Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011; 53(11):1120-6.

Haudek-Prinz, VJ, Klepeisz, P, Slany, A, et al. Proteome signatures of inflammatory activated primary human peripheral blood mononuclear cells. J Proteomics. 2012; 76:150-162.

Kleiveland, CR. Peripheral Blood Mononuclear Cells. In: Verhoeckx K. et al. (eds) The Impact of Food Bioactives on Health. Spring International Publishing; 2015.