Update on Inflammation and Cardiovascular Risk in People With HIV

Table of Contents

• Inflammation and HIV
• French Study Unexpectedly Uncovers Role of Substance Use in Heart Attacks
• VA Study Fingers Kidney Disease as a Major Predisposing Factor for Heart Attacks
• BICOMBO Study Looks at the Safety of Abacavir
• Cardiovascular Risk and HIV Treatment

Inflammation and HIV

In high-income countries and regions, such as Australia, Canada, Western Europe and the United States, highly active antiretroviral therapy (HAART) is widely available because of subsidized access. As a result, AIDS-related infections and deaths have greatly decreased. This effect of HAART is so immense that researchers expect that some HIV-positive people who can adhere to therapy and who have minimal co-existing complications can live near-normal life spans.

Viral Infections and Inflammation

A consequence of many viral infections is that the immune system is activated. This is a normal procedure that enables the immune system to go into a heightened state of alert and mobilize its forces against invading germs. Once an infection has been brought under control and the invading germs wiped out, the immune system then dampens down activation to a more normal state.

HIV infection activates the immune system very early in the course of infection. This activation appears to cause dysfunction within the immune system, also very early in the course of infection. Some researchers theorize that prolonged activation of the immune system due to HIV infection leads to increasingly dysfunctional behaviour by the immune system and, eventually, if treatment is not started, to the development of AIDS.

Although HAART is very good at suppressing HIV in the blood, infected cells continue to produce low levels of HIV in the body. And although the immune system continues to experience activation, albeit at a reduced level because of HAART, this continued activation over many years may gradually degrade organ-systems such as the heart and blood vessels, kidneys, bones, and so on.

Experiments conducted on monkeys infected with the AIDS-causing virus SIV and those in people taking HAART over the long-term confirm the presence of low-level activation. Because of the potential for continuous activation of the immune system to accelerate the ageing process, research teams in high-income countries are beginning to focus on this aspect of HIV infection. Their efforts are aimed at gaining a better understanding of why this activation occurs in the presence of HAART and developing ways to safely lessen it.

References

1. Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: cause and consequences. Journal of Pathology. 2008 Jan;214(2):231-41.
2. Grossman Z, Meier-Schellersheim M, Paul WE, et al. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nature Medicine. 2006 Mar;12(3):289-95.
3. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Medicine. 2008 Oct 21;5(10):e203.
4. Cadogan M, Dalgleish AG. HIV immunopathogenesis and strategies for intervention. Lancet Infect Diseases. 2008 Nov;8(11):675-84.
5. Herbeuval JP, Nilsson J, Boasso A, et al. HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques. AIDS. 2009 Jan 2;23(1):35-40.
6. Boasso A, Hardy AW, Anderson SA, et al. HIV-induced type I interferon and tryptophan catabolism drive T cell dysfunction despite phenotypic activation. PLoS One. 2008 Aug 13;3(8):e2961.