1. Proposed study on HIV and ageing As HIV mortality rates have dropped, an increasing proportion of individuals are living with HIV to older ages As HIV mortality rates have dropped, an increasing proportion of individuals are living with HIV to older ages Around 15% of individuals accessing HIV care in England and Wales in 2007 were aged >50 years Around 15% of individuals accessing HIV care in England and Wales in 2007 were aged >50 years There is a need to adapt the management of those living with HIV so that their clinical needs continue to be met There is a need to adapt the management of those living with HIV so that their clinical needs continue to be met However, virtually nothing is known about the likely health care needs of older HIV-positive persons However, virtually nothing is known about the likely health care needs of older HIV-positive persons

2. Study objective To create a nested, cohort of individuals aged >50 years, attending sites within the UK CHIC study and Dublin HIV cohort to address questions relating to several issues: - Uptake and outcomes of HAART in older individuals - ARV pharmacokinetics - Cardiovascular disease - Bone disease - CNS complications - Musculoskeletal manifestations - Women and the menopause - Sexual behaviour - Social and economic factors - CMV infection in compromising immunity during ageing - Resource utilisation

3. Proposed methods Nested cohort study within UK CHIC and Dublin HIV Cohort Cases: HIV-positive men and women aged >50 years from participating UK CHIC clinics/Dublin cohort

4. Proposed methods Nested cohort study within UK CHIC and Dublin HIV Cohort Cases: HIV-positive men and women aged >50 years from participating UK CHIC clinics/Dublin cohort Control group 1: HIV-positive men and women in three age groups (20-30, 30-40 and 40-50 years) attending participating clinics

5. Proposed methods Nested cohort study within UK CHIC and Dublin HIV Cohort Cases: HIV-positive men and women aged >50 years from participating UK CHIC clinics/Dublin cohort Control group 1: HIV-positive men and women in three age groups (20-30, 30-40 and 40-50 years) attending participating clinics Control group 2: Age-, sex-, ethnicity- and risk-group matched HIV-negative persons (identified from similar clinical settings)

6. Proposed methods Nested cohort study within UK CHIC and Dublin HIV Cohort Cases: HIV-positive men and women aged >50 years from participating UK CHIC clinics/Dublin cohort Control group 1: HIV-positive men and women in three age groups (20-30, 30-40 and 40-50 years) attending participating clinics Control group 2: Age-, sex-, ethnicity- and risk-group matched HIV-negative persons (identified from similar clinical settings) Fully consented study; no intervention Annual study visits Separately funded sub-studies as necessary (e.g. in-depth study of sexual behaviour)

7. Visit schedule BaselineYear 1Year 2Year 3Year 4 Baseline assessmentXxXxX Lifestyle and other factorsXXXXX Annual ScreenXXXXX Antiretroviral useXXXXX Clinical eventsXXXXX Healthcare useXXXXX Concomitant medicationsXXXXX Renal functionXXXXX Cardiovascular riskXXXXX Sexual BehaviourxXxXX TDMxxX Bone/fracture riskxxX CNS assessmentxxX PainxxX Social/economic factorsxxX Immunologyxxx

8. Visit schedule Baseline visit - Demographic data - Medical History - Educational Level - Lifestyle factors - Sexual behaviour - Use of ART - ECG - Thyroid function - Concomitant meds Annual assessment - Update on baseline data - Syphilis serology - HCV serology - LFTs - Renal function - Clinical events – diabetes, MI and other CV events, renal and liver problems, malignancies, fractures, osteoarthritis, gout, joint replacements - Falls assessment - Cardiovascular risk - Healthcare use

9. Visit schedule Biannual visits - Bone assessment (DEXA, fragility score, FRAX score, serum bone markers) - CNS assessment (Memory/cognitive motor function, quality of life, depression, serum biomarkers) - TDM - Pain assessment (pain questionnaire, serum urate) - Immunology (VZV/CMV serology and viral loads)

10. Current study team Marta Boffito (C&W) Alan Winston (St. Mary’s) Jane Anderson (Homerton) Ian Williams (MMC) Frank Post (Kings) Paddy Mallon (Dublin) Jonathan Elford (City University, epidemiologist) Karen Walker-Bone (Brighton) Arne Akbar (UCL, immunologist) Caroline Sabin (UCL, statistician/epidemiologist)

11. Questions Is this a study that patients would be keen to participate in? Is this a study that patients would be keen to participate in? If not, what might make it more attractive? If not, what might make it more attractive? Are there other medical issues that we should include? Are there other medical issues that we should include? How do we identify suitable controls? How do we identify suitable controls? Community involvement in study team? Community involvement in study team?