HIV and CVD: one step forward, two steps back?

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The human immunodeficiency virus (HIV) is a virus that damages the cells of the immune system, which weakens the body’s ability to fight off everyday infections and diseases. Global figures estimate that more than 35 million people are currently living with HIV. Acquired immunodeficiency syndrome (AIDS) is the term used to describe the most advanced stage of HIV infection and an individual is said to have AIDS when they have more than 20 opportunistic infections (i.e. infections that take advantage of a weakened immune system but are otherwise relatively harmless in healthy people) or HIV-related cancers. During the early stages of the HIV epidemic most deaths occurred as a result of opportunistic infections but the advent of antiretroviral therapy (ART) has changed that.

ART involves the use of a combination of antiretroviral drugs which suppress the growth of the virus and stop the progression of HIV, allowing the immune system of an infected individual to fight off opportunistic infections. ART also prevents the transmission of HIV and it is recommended that people who are at increased risk of HIV infection are given pre-exposure prophylaxis as an additional prevention method. Although the ART era has significantly improved survival rates it has also presented a new set of complications.

Most HIV related deaths occur due to chronic non-infectious diseases including cardiovascular disease (CVD). Over the past 20 years sub-Saharan Africa has seen a steady increase in the occurrence of CVD, which is interesting considering that 60% of the more than 35 million global incidences of HIV also occur in sub-Saharan Africa. Although the mechanism remains unclear, research has shown that there is a relationship between HIV infection and the development of CVD.  

Scientists including Dr Anoop Shah from the University of Edinburgh, in collaboration with research groups from Glasgow, Geneva, Munich, Cleveland and Baltimore, systematically reviewed and conducted a meta-analysis of the rate of CVD in people living with HIV in order to define the link between the two diseases. A meta-analysis is an analysis method used to generate quantitative data from related studies in order to produce results that summarise a whole body of research.  This study also sought to estimate the national, regional and global burden of HIV-associated CVD. Eighty original research papers that evaluated the relationship between HIV and CVD were analysed and the data used to produce a random effect meta-analysis.

Interestingly, Dr Shah and his colleagues found that the risk of developing CVD is twice as high for HIV-infected individuals. Furthermore, the number of CVD cases has risen by 300% over the past 20 years and is now accountable for 2.6 million Disability-adjusted life years (DALYs) per year. DALYs are an estimate of a specific disease burden which is expressed as the number of ‘healthy’ years lost due to ill-health. The results also show that there are large regional differences in the rates of HIV-associated CVD with most of the burden occurring in sub-Saharan Africa, followed by Asia and the Pacific.

There have been other studies that have evaluated the link between HIV and CVD as well as the possible role that ART may have. The work conducted here though, is the first to review and conduct a systematic meta-analysis to investigate the link between HIV infection and CVD and to estimate how much of the burden of CVD is due to HIV. The biological mechanism underlying this relationship is not well understood but it is generally thought that individuals living with HIV have increased systemic and coronary inflammation, malfunctioning arteries and increased circulating inflammatory markers which contribute to the increased CVD risk.

The global burden of HIV-associated CVD has risen 3-fold in the past 20 years which has significant implications for regional health policies, resource allocation and treatment guidelines. It has been suggested that people living with HIV should be considered high risk and should therefore be treated with statins, a group of medicines which are known to reduce cholesterol levels and have been found to reduce the risk of CVD in those who are at high risk of developing the disease. The REPRIEVE study (Randomised Trial to Prevent Vascular Events in HIV) is currently being conducted in order to determine whether statin therapy would effective in people living with HIV.

The clinical care of people living with HIV is undergoing major changes as is our understanding of the interplay between HIV and CVD as well as HIV and other HIV-associated disorders. In the future, CVD may end up disproportionately affecting people living with HIV. This presents a challenge and an opportunity which necessitates a coordinated multidisciplinary approach to positively influence the future of HIV clinical care and public health intervention.

This article was written by Zandile Nare and edited by James Hitchen.

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