HIV, Active HCV, Low Income Tied to Shorter Telomeres, a Cellular Aging Marker

HIV, Active HCV, Low Income Tied to Shorter Telomeres, a Cellular Aging Marker


HIV, Active HCV, Low Income Tied to Shorter Telomeres, a Cellular Aging Marker
3rd International Workshop on HIV and Aging, November 5-6, 2012, Baltimore

Mark Mascolini

HIV infection, active HCV infection, and income below $15,000 a year independently predicted shorter telomere length in a study of 229 HIV-positive people and 166 HIV-negative people in a Vancouver cohort [1]. HIV infection had a slightly greater negative impact on telomere length than 10 years of age.

Telomeres cap the ends of chromosomes and shield them from damage. Shrinking with each cell division, telomeres shorten with age. Thus telomere length offers a marker of cellular aging. Telomeres may shorten more rapidly than normal when exposed to the oxidative stress resulting from HIV-induced inflammation, chronic immune activation, or treatment with antiretrovirals. And antiretroviral therapy itself may inhibit telomere activity.

To assess the impact of HIV and non-HIV variables on leukocyte telomere length, researchers conducted this prospective study of adults between 19 and 75 years old enrolled in the Vancouver’s CARMA cohort between 2008 and 2011. Heterosexual sex and injection drug use are the prime routes of HIV acquisition in this socioeconomically disadvantaged study group.

The study included 229 HIV-positive people and 166 HIV-negative people, most of them women (79% and 71%). The HIV-positive and negative people were similar in age (median 40 and 38). The HIV group had a significantly higher proportion of blacks than the HIV-negative group (17% versus 1%, P < 0.01). Proportions of participants with an annual income below $15,000 were 45% in the HIV group and 54% in the HIV-negative group, a nonsignificant difference (P = 0.51).

Maternal age at the cohort member’s birth was slightly but significantly lower in the HIV group than in the HIV-negative group (24 versus 26, P = 0.02), but paternal age at birth did not differ significantly by HIV status. The researchers had maternal and paternal age data for only half of the study group, so these variables were not included in the final multivariate model.

HIV-positive people had a median HIV infection duration of 9 years and a median lifetime antiretroviral duration of 4 years. Median nadir and current CD4 counts were 190 and 450, and 60% of HIV-positive people had an undetectable viral load at the study visit.

Univariate statistical analysis identified several factors associated with shorter telomere length: HIV infection (P = 0.031), HCV infection (P < 0.0001), income below $15,000 (P = 0.0002), having an older father or mother at birth (P = 0.0006 and P = 0.029), being black versus white (P = 0.031), being South Asian versus white (P = 0.018), older age (P < 0.0001), pack-years smoking (P = 0.017), and illicit drug use (P < 0.0001). Smoking, illicit drug use, and low income were associated with shorter telomere length only in HIV-negative people.

In the final multivariate analysis including HIV-positive and negative people, four variables were independently associated with shorter telomere length:

— Every 10 years of age, beta -0.24, < 0.0001
— HIV infection, beta -0.28, P = 0.004
— Active HCV infection, beta -0.24, P = 0.004
— Annual income below versus above $15,000, beta -0.32, P = 0.001

Cleared HCV infection did not predict shorter telomere length. Among the 229 people with HIV infection, shorter telomere length was not linked to current CD4 count, CD4 nadir, time since HIV diagnosis, antiretroviral duration, or number of treatment interruptions. Nor did those factors predict telomere length in 126 HIV-positive people with an undetectable viral load.

The Vancouver team concluded that–besides older age–HIV infection, active HCV infection, and low income predict shorter telomere length and “may therefore affect telomere maintenance and cellular aging.” Because the beta value for HIV exceeded that for 10 years of age (-0.28 versus -0.24), they suggested that HIV infection has a greater impact on telomere shortening than a decade of age. The researchers speculated that low income may be a surrogate for lifestyle and environmental factors that directly affect telomere length.

The investigators proposed that the link between active HCV infection and shorter telomeres may mean ongoing HCV-induced immune activation or inflammation could affect leukocyte telomere length. They suggested that future research should weigh the impact of anti-HCV therapy on telomere length.

A workshop attendee observed that the study measured telomeres in all leukocytes–the collection of white cells in which granulocytes predominate. Lymphocytes (which include T cells) make up about 30% of leukocytes.

1. Zanet D, Thorne A, Sattha B, et al. Active hepatitis C virus (HCV) infection, HIV+ status and low income are associated with shorter leukocyte telomere length in a cohort of HIV+ and HIV- adults. 3rd International Workshop on HIV and Aging. November 5-6, 2012, Baltimore. Abstract: O_07.

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