Issues That Divide Expert Opinion: When to Start, HIV and Aging and the Impact of HIV on Life Expectancy
The impact and association of HIV and ageing was the second topic discussed in Glasgow upon which experts hold diverse opinions. Again, these views impact on clinical decisions, including whether to start earlier treatment. At one extreme, the question of whether HIV directly contributes to significantly faster ageing and increased comorbidities, even in the context of stable treatment -- or whether previous reports of early or premature ageing can be explained by the difficulty of identifying appropriate HIV negative control populations?
Several important research groups have contributed to this debate. In July 2012, a supplement to JAIDS, published to coincide with the IAS conference in Washington DC, reviewed four key areas on HIV and ageing. This included the mechanisms for functional decline in innate and adaptive immunity in HIV positive people, the evidence for increases in some biomarkers associated with both HIV and ageing, the role of comorbidities and the diverse behavioural and socio-economic factors that make the HIV positive population such a complex demographic group. While acknowledging that ART increased life expectancy to 70 years, the paper focused on why this hasn't normalised to HIV negative levels. It also proposed key research challenges that need to be prioritised in order to answer these questions.4
At CROI 2012, Amy Justice, from the Veterans Affairs Healthcare System (and a co-author of the JAIDS review), emphasised the difference between the potential role of HIV in both "accelerated ageing" (where comorbidities might be occuring at an earlier age) and "accentuated ageing" (where they occur at a higher rate) -- and that these effects are not mutually exclusive. This oral presentation also reported the data showing how the lack of adjustment for the younger age of HIV positive compared to general population cohorts, can explain studies that previously suggested HIV positive people might age 20-30 years earlier than HIV negative people.4
In Glasgow, Peter Reiss, from the University of Amsterdam, the Netherlands (a co-author of the JAIDS supplement on ageing and a member of both EACS and IAS-USA guideline panels), presented an overview on the potential mechanisms for how HIV might negatively interact with comorbidity and ageing.5
As background, many Western epidemics are approaching the time where more than half the HIV positive population will be older than 50 years old, and that the exponential increase in chronic conditions commonly identifies age as the single strongest risk. This includes cardiovascular, renal, pulmonary and hepatic disease, bone health, neurocognitive function, diabetes and frailty.
Concerns about HIV and ageing are especially focused on people who initiated treatment at lower CD4 counts, who are less likely to achieve CD4 counts >500 cells/mm3 on treatment, often due to late presentation. Adjustment for the younger age of HIV positive cohorts has explained earlier reports that HIV positive people developed non-AIDS cancers at an earlier age.6 However, several studies have also reported that there is greater use of concomitant medications at an earlier age (polypharmacy) -- though this may be driven by the better care and more frequent monitoring that HIV positive people receive.7
Prior to treatment, immunologic disruption, HIV and CMV replication, the loss of mucosal gut integrity and microbial translocation, all contribute to a heightened state of immune activation. Although greatly reduced on ART, residual activation may maintain an inflammatory state that continues to increase the risk of fibrotic and coagulant states and these are associated with higher comorbidites. The degree to which this accelerates a healthy ageing process, that by definition involves changes in immune function and tissue and cellular structure, is for research to establish.
So, however compelling and plausible the concerns from inflammation appear, Reiss emphasised that these concepts currently remain a hypothesis that needs to be either proven or refuted -- and that this is already the focus of several large studies. Until then, lifestyle choices (including diet, exercise, quitting smoking) may be able to ameliorate many of these additional risks factors that contribute to comorbidity in HIV positive people, just as they do in the general population. And that the issue of HIV and ageing, will become increasingly important globally.
This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.
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