HIV & Ageing - A Review AFAO Educator’s Conference 25 May 2010

Overview

• Unpack the “term” – which is multi faceted• Scientific understandings / theories• Role of HIV & Effects of long term treatments• Various age related conditions • Various HIV related conditions• Clinical & Service delivery implications

Analysis and review

• “Body of evidence” – Past several years the evidence base has been building / review of current literature and forthcoming

• Sherr, L et al: (2009) Clinical and behavioural aspects of Ageing with HIV; Psychology, Health and Medicine 14:3, 273 -279

• Deeks SG, Phillips AN: (2009) HIV Infection, ARV Treatments, Ageing and non AIDS related morbidity. BMJ 2009, 338

Relevance

• “In treated patients who have suppressed HIV, natural ageing, drug specific toxicities, lifestyle factors, persistent inflammation, and residual immunodeficiency are causally associated with premature development of many complications normally associated with ageing.” Deeks SG, Phillips AN: (2009) HIV Infection, ARV Treatments,Ageing and non AIDS related morbidity. BMJ 2009, 338

Analysis & Review

• CROI presentations (Feb 2010)• Ances B, et al; (Feb 2010) HIV Associated CNS

complications. Journal of Infectious Diseases;2010;201: 336 – 340

• Neuhaus et al; (Feb 2010) Various SMART reports – Persistent immune activation / inflammation. Current HIV/AIDS Reports, 2010, 4

Analysis and Review

• Justice A; (April 2010) HIV & Ageing – Time for a new paradigm. Current HIV/AIDS Reports 2010, 7: 69 - 76

• Ganesan A, et al / Baker J, et al (Jan 2010); Inflammation and complications of HIV Disease; JID 2010; 201: 272 – 284, 285 - 292 – (2 Papers)

Relevance

• For PWHIV The immune system has persistent defects – and many are similar to those seen in normal ageing, but they occur at an earlier age than normal.

• Persistent (chronic) inflammation – cellular senescence = accelerated ageing by disrupting normal tissue and cellular functions

Relevance

• In general population – ageing is associated with a decline in immune function

• Ageing is associated with increases in disease susceptibility

• The natural history of HIV in older people may be unique

• After trying to boost immune responses – is it now about suppressing the immune response?

Premature ageing

• Inflammation – chronic and low level• Implicated in atherosclerosis, impaired blood

flow • In turn this contributes to heart and kidney

disease, as well as cognitive function impacts• Theories include HIV associated immune

activation

Primary co-morbidities

• Reports of increased risk, even in the presence of viral suppression:

• Heart disease• Kidney disease• Cancers • Bone weakness and frailty

Multiple co-morbidities: HIV versus controls

Guaraldi G et al. CROI 2010. Abstract 727

Comorbidities analysed: hypertension, Type 2 Diabetes Mellitus, Cardiovascular disease and osteoporosis Guaraldi G, CROI 2010 Abstract727

Virus / Body / Drugs: some recent theories

• HIV causes permanent damage to the body and its immune system in the first days – to weeks of infection

• Leaky gut theory – whereby a body wide immune response to the HIV attack in the intestinal tract causes the destruction of a large amount of the CD4 T-cell reserves, and this is never recovered

• Immune capacity slowly and permanently diminishes over time as HIV replication persistently erodes CD4 population

• This would mean that the lowest CD4 baseline of a person may become an important predictor for premature ageing

• Low levels of HIV can contribute to altered immune regulation

• Even when replication may be halted by drugs, and undetectable, HIV is not completely destroyed in the body (viral reservoirs)

• Viral proteins can signal immune response – inflammation caused by a “semipermanent activation”

•With long term treatment and associated toxicities there may be metabolic disorders that are still not clear re. bone and fat impacts

• All the drugs are possibly implicated and no studies have yet been conducted that might reveal roles in premature ageing

Current research:

- Looking at NRTI avoidance- Looking at intensification – to try and push HIV

even lower than currently considered Undetectable levels

- Immune suppressant approaches to reduce inflammation

- CD4 cell renewal (ie: IL-7)

- New types of drugs and assays to try and determine ongoing immune damage despite viral control

- START – looking for conclusive evidence that any period of uncontrolled HIV replication is harmful, and that treatment should start as soon as virus is diagnosed

- Telomerase activators – to slow ageing of cells

Challenges

• If primary infection causing the most damage – then it may be too late to repair the immune cell function

• PREP - just to “Blunt” the initial impact, rather than prevent

• CD4 counts are only very general indicators of immune capacity, need to understand what, and how to intervene before CD4 levels begin to drop

Where to from here?

• Evidence base to start building our Australian responses

- Need to logitudinally follow patients to collate morbidities and guide care

- Progress development of Care guidelines, beyond the ARV guidelines (more than just drugs)

- Complex chronic care management issues for primary care interface and work already ongoing for MOC evaluations

Clinically

•Maximise functional status•Minimise frailty• Prolong life expectancy with Q of L• Educate patients and Drs for best outcomes• Implications for ongoing clinical education and

HIV health promotion

Advocacy

• Research agendas and study design implications

• Regulatory issues• New screening tools / immune modulation

and drug interventions• Improving links with aged care sector

Current NAPWA Activities• Policy & Advocacy

o Various submission processes and reviewso Models of Care ongoing – Across clinical sites and BBVSS processo Clinical Auditso Presentations across various for ao Models of Care – Complex Chronic Disease and HIV Specific

• Researcho AHOD Linkage NHMRC granto NAPWA Modelling studyo NHMRC Partnership application – Chronic Illness ando Patient interventionso Neurohart and HANDo Immune based / antiinflammatory therapies pipeline

Key areas / Objectives

• How to talk issues and make distinctions across the plethora of issues

• Population progressively ageing and experiencing various non-AIDS diseases

• But concurrently HIV disease long term / HIV Treatments long term, and HIV associated demographics also strong influences on outcomes

Next steps

• Upcoming NAPWA forum – June 2010Priority outcomes

• Strategies for advocacy through HIV Strategy and broader DOHA

• Review of analysis and data • Priorities for action• Future updates / reporting timelines

Conclusion

• HIV shifted to a disease of more complex chronic issues

• A new frontier for people now living with more unknowns re. premature ageing – various degenerations of mind and body which is more than a “getting older” concern and which will determine Q of L over many years

• A challenge that we have to now focus

www. .org.au