1) HIV patients are now living long enough to develop non-AIDS related conditions like heart disease, cancer, and stroke. While ART has reduced AIDS deaths, other causes of death are more common. 2) Studies show HIV patients have a higher risk of heart disease and other non-AIDS conditions at all ages compared to those without HIV. Risk factors like smoking, high blood pressure, and high cholesterol still apply. 3) To reduce risks, patients should stop smoking, monitor blood pressure and lipids, exercise, and discuss earlier ART treatment with their doctor.

1. Ageing with HIV Gordon Scott GUM consultant

2. I’m very pleased to be giving this talk In the early years of the epidemic, patients would only ask questions like Will I live to see my 30 th birthday? Should I cash in my pension now? Will this be my last Christmas?

3. Deaths due to AIDS AIDS was defined when a patient was diagnosed with a specific condition associated with immunosuppression caused by HIV In these early years before highly active antitretroviral therapy (HAART), patients tended to die relatively quickly from AIDS-related causes HAART has reduced HIV/AIDS-related mortality to extremely low levels Now usually seen in late presenters only Most people living with HIV therefore die of the same things that kill everyone else

4. What are the main causes of death in Scotland? Cancer Heart disease Stroke All of these are more common as we get older

5. HIV versus non-HIV Although the risk of heart disease and other non-AIDS conditions increases with age in patients with or without HIV infection, these diseases are more common at all ages in HIV-positive populations compared to people without HIV For example, the risk of heart disease is between 1.5 and 2 times greater for HIV versus non-HIV cohorts

6. SMART study Maybe taking ART long term is bad for you Patients on ART stopped treatment when CD4 was greater than 350, and restarted when CD4 fell to less than 250 Compared to patients who continued ART There was a greater risk of dying in those who stopped and started ART Mainly non-AIDS related conditions

7. Why might uncontrolled HIV have these consequences? Immunosuppressed patients have an increased risk of cancer There will be residual immune suppression even after starting treatment Untreated HIV causes inflammation Inflammation increases the risk of atherosclerosis (furred up/hardened arteries) This can cause heart attacks and strokes Untreated HIV can cause dementia

8. Cardiovascular (Heart) disease (CVD) Commonest cause of death in Scotland Although rates have fallen substantially over the last 20 years Classic risk factors were identified in the Framingham study which started in 1949 Small town in Massachusets USA

9. Framingham study The researchers recruited 5,209 men and women between the ages of 30 and 62 and began the first round of extensive physical examinations and lifestyle interviews In 1971, the study enrolled a second generation (5,124) of the original participants' adult children and their spouses; and in 2002 the grandchildren of the original cohort were enrolled. As people suffered heart attacks and/or strokes, researchers reviewed lifestyle factors, examination findings and blood test results with comparable neighbours

10. Framingham continued The major CVD risk factors were identified High blood pressure High blood cholesterol Smoking Obesity Diabetes Physical inactivity Although – do these calculations apply in other populations? How relevant are the findings in patients with HIV?

11. Framingham CVD disease calculator Gender Male Age 35 Family history No BP Normal Lipids Normal Smoker No Diabetes No Risk 1% Gender Male Age 55 Family history No BP Normal Lipids Normal Smoker No Diabetes No Risk 4%

12. Gender Male Age 55 Family history No BP Normal Lipids Normal Smoker Yes Diabetes No Risk 8% Gender Male Age 55 Family history Yes BP Normal Lipids High Smoker No Diabetes No Risk 16%

13. Does ART itself increase risk of CVD? Protease inhibitors increase lipids (Efavirenz also increases cholesterol, but mainly good HDL cholesterol) DAD study

14. Recent French study (CHIC) presented at CROI conference CVD was associated with length of HIV infection regardless of ART So maybe the DAD graph just reflects the increasing risk because you have had HIV longer Another Californian study suggested that lower CD4 was associated with CVD Probably not surprising as this is usually a reflection of length of HIV infection

15. What about abacavir? DAD study suggested increased risk of CVD in patients taking abacavir Recent research (also presented at CROI) concluded that this was not so

16. What can you do? You can’t change your parents/ancestors! You can stop smoking Being on ART is better than not being on ART You can get your lipids and BP measured, and take treatment if either or both are elevated

17. Reducing risk of cancer Stop smoking Take up the offer of screening aimed at the general population Cervical smears for women Breast screening Bowel cancer screening ?anal smears for men Anal cancer is more common Less evidence for benefit of screening

18. Bones HIV is associated with reduced bone mineral density Possibly secondary to inflammation low testosterone levels, low body weight, smoking, and drinking alcohol may also play a role Low vitamin D levels are seen in some HIV patients ART is clearly associated with bone loss Protease inhibitors NRTIs But no convincing evidence of increased fracture rate

19. Brain – risk of dementia? Some studies from the USA say that half of patients with HIV have “neurocognitive impairment” However recent studies from London suggest otherwise Only 19% HIV-positive adults stable on ART showed any effect (compared to 16% HIV-negative) Young people born with HIV performed as well as HIV-negative controls Anxiety and depression can affect performance in assessment, and may explain previous findings

20. Frailty There is some association between HIV and frailty Reduced strength Exhaustion Slowness Unplanned weight loss Reduced physical activity Probably reflects degree/duration of immune failure and inflammation

21. What should you do? The same things everyone should do Don’t smoke Alcohol in moderation Maintain a healthy weight/good diet Exercise Have blood pressure and lipids measured Accept recommended treatment

22. Is there anything specific to HIV that you should do? Earlier treatment confers long term benefit with regard to non-AIDS mortality Definite benefit from starting with CD4 of around 350 Possible benefit if CD4 is 350-500 Maybe even a minor benefit between 500 and 650 Discuss this with your doctor

23. Enjoy life as much as you can Otherwise you could end up being miserable for a lot longer than you had expected!