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HIV Duration, Not ART, Tied to Atherosclerosis Marker in Large Case-Control Study
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
Longer duration of HIV infection--but not antiretroviral therapy (ART)--correlated with greater carotid artery intima media thickness (cIMT) in a case-control study that involved only male nonsmokers [1]. This three-way comparison of antiretroviral-treated men, antiretroviral-naive men with HIV, and men without HIV also associated a high anti-inflammatory marker profile with thinner (less risky) cIMT.
Previous studies assessing correlations between HIV, antiretroviral therapy, inflammatory markers, and cIMT either lacked an HIV-negative control group or could not eliminate statistical confounding by smoking. To avoid those shortcomings, collaborators in France planned this cross-sectional case-control comparison to distinguish between the impact of HIV and antiretroviral therapy on cIMT in men who never smoked.
From March 2008 through June 2009, the researchers enrolled 50 people in each of three groups:
Antiretroviral-treated group: 50 men older than 35 taking combination antiretrovirals for at least 4 years and with a viral load below 400 copies/mL
Antiretroviral-naive group: 50 men matched by age (+/- 5 years) to the antiretroviral group and infected with HIV for at least 2 years but naive to ART because they did not meet current indications for starting therapy
HIV-negative control group: 50 men matched by age (+/- 5 years) to the antiretroviral-treated group
Everyone had a Karnofsky score above 80, indicating relatively good overall health, and no one had a history of heart disease or stroke, active viral hepatitis within 1 month, chemotherapy, radiotherapy, systemic corticosteroid therapy, or treatment with interferon or adefovir. The investigators measured cIMT by high-resolution ultrasound at 12 carotid sites outside plaque areas. All study participants answered a questionnaire on factors affecting immunity and risk taking.
For each person the researchers calculated proinflammatory and anti-inflammatory profiles by summing scores of proinflammatory markers (hsCRP, resistin, IL-6, IL-18, insulin, serum amyloid A, and d-dimer) and anti-inflammatory markers (total and high molecular weight adiponectin, IL-27, and IL-10). Finally, the investigators compared cIMT across the three groups in analyses stratified by HIV duration or inflammation profile and adjusted for age, diabetes, and prior hypertension.
Age in the HIV-positive group averaged 41.2 years, 70% were European in origin, and none had diabetes or hypertension. Duration of HIV infection averaged 14.1 years in the antiretroviral-treated group with more than 7.9 years of known HIV infection, 6.3 years in the antiretroviral-treated group with fewer than 7.9 years of HIV infection, 11.5 years in the antiretroviral-naive group with more than 7.9 years of HIV infection, and 3.8 years in the antiretroviral-naive group with fewer than 7.9 years of HIV infection. Duration of antiretroviral therapy averaged 9.9 years in the group with more than 7.9 years of known HIV infection and 5.9 years in those with a shorter duration of infection. Viral load averaged under 50 copies in the antiretroviral-treated group and around 1000 copies in the naive group.
An analysis that eliminated one antiretroviral-naive person with a viral load under 50 copies and adjusted for lowest-ever CD4 count found thicker (higher-risk) cIMT with HIV duration over 7.9 years, regardless of antiretroviral exposure:
Average cIMT
ART-experienced and over 7.9 years HIV duration: 760 +/- 10 microM
ART-experienced and under 7.9 years HIV duration: 731 +/- 16 microM
ART-naive and over 7.9 years HIV duration: 757 +/- 17 microM
ART-naive and under 7.9 years HIV duration: 731 +/- 10 microM
People with a high anti-inflammatory profile and a low pro-inflammatory profile had the lowest cIMT in three statistical models (between 0.70 and 0.72 microM), followed by people with a high anti-inflammatory profile and high proinflammatory profile (between 0.72 and 0.74 microM), people with a low anti-inflammatory profile and high proinflammatory profile (around 7.60 microM), and people with a low anti-inflammatory profile and low proinflammatory profile (between 0.74 and 0.78 microM). Total adiponectin, an anti-inflammatory marker, dropped as duration of HIV infection increased (P = 0.002).
The investigators conclude that HIV infection duration--and not exposure to antiretrovirals--is associated with thicker cIMT in HIV-positive men who have never smoked. That result suggests that HIV itself, not its treatment, heightens the risk of atherosclerosis in nonsmoking men. High levels of anti-inflammatory markers appeared to protect against thicker cIMT.
Reference
1. Desvarieux M, Meynard L, Boccara F, et al. Carotid atherosclerosis is related to HIV duration and anti-inflammatory profile and not to ARV exposure: the CHIC controlled study. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 803.
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