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


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.
Hsue
Priscilla Y
PY
Division of Cardiology, San Francisco General Hospital, San Francisco, California 94110, USA. phsue@medsfgh.ucsf.edu
Hunt
Peter W
PW
Schnell
Amanda
A
Kalapus
S Craig
SC
Hoh
Rebecca
R
Ganz
Peter
P
Martin
Jeffrey N
JN
Deeks
Steven G
SG
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D050197:Atherosclerosis / Q000276:immunology* / Q000821:virology; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017539:Tunica Intima / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology*