Impact of age on markers of HIV-1 disease

Abstract

Aging is a complicated process characterized by a progressive loss of homeostasis, which results in an increased vulnerability to multiple diseases. HIV-1-infected patients demonstrate a premature aging phenotype and develop certain age-related diseases earlier in their lifespan than what is seen in the general population. Age-related comorbidities may include the development of bone disease, metabolic disorders, neurologic impairment and immunosenescence. Age also appears to have an effect on traditional markers of HIV-1 disease progression, including CD4⁺ T-cell count and viral load. These effects are not only a consequence of HIV-1 infection, but in many cases, are also linked to antiretroviral therapy. This review summarizes the complex interplay between HIV-1 infection and aging, and the impact that aging has on markers of HIV-1 disease.

Keywords: HIV-1; aging; comorbidities; disease progression; neurocognitive impairment.

Figure 1. HIV-1 infection initiates a premature aging response

Normal aging-related disease states that are observed in the elderly occur at much younger ages in HIV-1-infected patients. These disease states include enhanced neurologic decline, metabolic/cardiovascular diseases including dyslipidemia, lipodystrophy and diabetes, immune system dysfunction and bone disease. HAART also seems to play a role in premature aging.

Figure 2. Immune regulation in response to aging and HIV-1 infection

As an individual ages, immune competence declines and changes occur in the overall function of the immune system. With aging, the number of terminally differentiated CD8⁺ T cells increases, while their ability to proliferate decreases and CD28 expression decreases. There are also fewer naive CD8⁺ T cells. Aging also decreases the number and function of CD4⁺ T cells. This decrease has also been shown to lead to a decrease in the overall CD4⁺:CD8⁺ T-cell ratio. HIV-1 infection itself also induces changes in the overall number and function of CD4⁺ T cells, increasing the number of terminally differentiated CD8⁺ T cells and decreasing the ability of CD8⁺ T cells to proliferate. Even though the number of CD4⁺ T cells decreases, the number of memory CD4⁺ T cells increases; however, these memory cells are less able to respond to pathogens. Blood monocytes and tissue macrophages typically have a decreased level of activation in older, uninfected patients. Large increases have also been shown in CD14⁺/CD16⁺ receptors on mature monocytes in the elderly. This was similar to what was observed in younger HIV-1-infected patients. Within both the older uninfected population, as well as HIV-1-infected patients, macrophages appeared to have diminished microbicidal capability. However, not all aging-related changes have centered on a loss of function. IL-6 cytokine levels increase with aging, as well as independently with HIV-1 infection. p55- and p75-soluble TNF-α receptor levels also increase. These levels all increase further in HIV-1-infected patients as they age.