1. HIV and STI Department - Centre for Infections Predictors of non-AIDS related death in a national cohort of HIV-diagnosed adults Meaghan Kall, Ruth Smith, Alison Brown, Valerie Delpech Health Protection Agency

2. HIV and STI Department - Centre for Infections Introduction Dramatic declines in AIDS-related mortality since effective ART Mortality rates among HIV-infected persons are now approaching those of the general population Yet ~600 HIV-infected persons die annually in the UK, just under 1% of HIV-diagnosed population  half AIDS-related

3. HIV and STI Department - Centre for Infections Aims Estimate frequencies and incidence of non-AIDS deaths among HIV-infected individuals since ART Identify factors associated with non-AIDS related death

4. HIV and STI Department - Centre for Infections Population: Adults (age 15+) diagnosed with HIV and seen for HIV care between 1997-2010 in England and Wales Design: Retrospective observational cohort study Data: national HIV surveillance data matched to death records from the Office for National Statistics. Details include date of death and up to 6 cause of death codes (ICD9/10). Statistical Analysis: Multivariate Cox regression models used to estimate hazard ratios for predictors of non-AIDS death Methods

5. HIV and STI Department - Centre for Infections Death Classification All Cause Deaths AIDS Related Non-AIDS Related Non-AIDS defining infections Non-AIDS malignancies Liver disease (including liver cancer) Cardiovascular disease and stroke Accident or SuicideOther causes Excluded: Cause of death unknown

6. HIV and STI Department - Centre for Infections 70,914 patients diagnosed and under follow-up between 1997 and 2010  319,082 person-years follow-up 3,814 (5.4%) died Definitive cause of death assigned for 3,594 (94%) 50.2% (1,804/3,594) died of non-AIDS related causes Results

7. HIV and STI Department - Centre for Infections Characteristics of non-AIDS related deaths: England &Wales, 1997-2010 (n=1,804) VariableCategoryNo. of Deaths (%) SexMale1,358 (73%) Infection Route Heterosexual contact843 (47%) MSM 731 (41%) Injecting drug use165 (9.0%) Other65 (3.6%) TreatmentEver on HAART1269 (70%) Age at DeathMedian [IQR]43 (36-51) Years Lived Since DiagnosisMedian [IQR]2.5 (0.6 – 5.4) Previous AIDS DiagnosisYes455 (25%) Late Diagnosis (CD4 within 91 days) CD4 <350929 (50%)

8. HIV and STI Department - Centre for Infections Crude mortality rates: England and Wales, 2010 Per 1,000 population aged 15-59 General Population (all cause)1.6 HIV-infected population (Non-AIDS cause of death) 3.6

9. HIV and STI Department - Centre for Infections Frequency and Crude Incidence Rates by Specific Cause of Death: 1997 -2010 (n=1,804) Cause of Death Number of Deaths Rate (95% CI) per 1000 years All-cause3,81411.3 (11.0-11.7) Non-AIDS (all)1,8045.6 (5.3-5.8) Non-AIDS infections4481.31 (1.19-1.44) Cardiovascular/Stroke3090.93 (0.83-1.04) Non-AIDS malignancy2830.85 (0.76-0.96) Accident/Suicide2670.80 (0.71-0.90) Liver disease1440.44 (0.37-0.52) Other3531.14 (1.02-1.26)

10. HIV and STI Department - Centre for Infections Predictors of non-AIDS related death: England &Wales, 1997-2010 Compared to MSM Heterosexual contactHR 1.40 (1.21-1.62)p<0.001 Injecting drug useHR 4.17 (3.46-5.01)p<0.001 Compared to age <25p<0.001 Age 25-35HR 1.38 (1.10-1.74) Age 35-49HR 2.34 (1.87-2.94) Age 50+HR 4.71 (3.70-6.00) Diagnosed lateHR 1.15 (1.03-1.27)p=0.01 Previous AIDS diagnosisHR 2.13 (1.89-2.39)p<0.001 ART < 3 yearsHR 3.08 (2.75-3.45)p<0.001 NS: Sex, ethnicity, year of diagnosis

11. HIV and STI Department - Centre for Infections Limitations Under-reporting of deaths Misclassification of AIDS and non-AIDS Future work: –Improved classification of cause of death Large European initiative (CoDe) + algorithm –Cause-specific mortality analysis –Case-control study

12. HIV and STI Department - Centre for Infections Conclusions Non-AIDS causes account for half of deaths among HIV-infected adults Mortality rates are twice that of the general population. Treatment exposure and a previous AIDS diagnosis were strong predictors of non-AIDS related death Prompt HIV care could reduce all-cause mortality of people living with HIV, not only AIDS-related deaths

13. HIV and STI Department - Centre for Infections Acknowledgements The continuing collaboration of those who contribute to HIV surveillance in the UK is gratefully acknowledged. Without their generosity, time and effort the current level of understanding of the epidemic could not have been obtained.