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

AIDS. 2009 Jun 1;23(9):1059-67. doi: 10.1097/QAD.0b013e32832b514b.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active*
  • Atherosclerosis / immunology*
  • Atherosclerosis / virology
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • HIV Seropositivity / drug therapy
  • HIV Seropositivity / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immune Tolerance / immunology*
  • Male
  • Middle Aged
  • Risk Factors
  • Tunica Intima / immunology*
  • Tunica Intima / virology
  • Viral Load
  • Virus Replication / immunology*