Role of viral replication, antiretroviral therapy, and... : AIDS (original) (raw)

BASIC SCIENCE

Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis

Hsue, Priscilla Ya; Hunt, Peter Wb; Schnell, Amandaa; Kalapus, S Craiga; Hoh, Rebeccab; Ganz, Petera; Martin, Jeffrey Nb,c; Deeks, Steven Gb

aDivision of Cardiology, USA

bDivision of Positive Health Program of the Department of Medicine, San Francisco General Hospital, USA

cDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.

Received 30 December, 2008

Revised 13 February, 2009

Accepted 3 March, 2009

Correspondence to Priscilla Y. Hsue, MD, Room 5G1, Division of Cardiology, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, USA. Tel: +1 415 206 8257; fax: +1 415 206 5100; e-mail: [email protected]

Abstract

Objective:

HIV-seropositive patients are at higher risk for atherosclerosis than HIV-seronegative persons. This has been variably attributed to antiretroviral drug toxicity, immunodeficiency, and/or HIV-associated inflammation. To evaluate the contributions of these factors to HIV-associated atherosclerosis, we assessed carotid artery intima-media thickness in a diverse cohort of HIV-seronegative and seropositive adults, including a unique group of HIV-infected patients who were untreated, had undetectable viral loads, and had preserved CD4+ T-cell counts (HIV controllers).

Methods and results:

Carotid intima-media thickness was measured in 494 participants, including 33 HIV controllers and 93 HIV-seronegative controls. HIV controllers had higher intima-media thickness than seronegative controls even after adjustment for traditional risk factors (P = 0.003). Intima-media thickness in controllers was similar to antiretroviral-untreated patients with detectable viremia. Across all participants, intima-media thickness was strongly associated with the presence of HIV disease rather than viral load or CD4+ T-cell count. C-reactive protein was higher in HIV controllers than HIV-seronegative persons. Antiretroviral drug exposure was also associated with higher intima-media thickness.

Conclusions:

Increased atherosclerosis with HIV infection can occur in the absence of antiretroviral therapy, detectable viremia, or overt immunodeficiency. Chronic inflammation – which is higher in controllers than in HIV-uninfected persons – may account for early atherosclerosis in these patients.