Life expectancy of patients treated with ART in the UK: UK CHIC Study Margaret May University of Bristol, Department of Social Medicine, Bristol

Background UK CHIC Life expectancy (LE) is an important population health indicator that varies by country –Previous analyses of LE in HIV-1 infected individuals by ART- CC included few patients from UK (Royal Free only) and were averaged over several countries Lancet 372(2008): For patients, knowing LE may affect lifestyle decisions: –Whether to have children, treatment for co-morbidities, save for a pension… LE is also important for public health planning –estimating health burden of lifetime treatment with cARTg LE can be used by policy makers –Eg offers of life insurance depending on LE Mortgage and housing, providing for dependents

Aims UK CHIC To estimate for the UK population of HIV-1 infected individuals: Mortality rates (per 1000 pyears) –Overall –Between the ages 20 and 44 years Potential years of life lost (PYLL) before age 65 (per 1000 pyears) Life expectancy –At exact ages 20 and 35 –Percentage of patient surviving from 20 to 44 years

Aims UK CHIC To estimate these health indicators overall and by: –Period of follow up , , , –Gender and ethnicity White males, non-white males, white females, non-white females –CD4 cell count at start of cART <100, , cellscells/mm 3 –Year of starting cART , , To estimate these health indicators in those who survive at least 6 months from start of cART

Patients included in analysis UK CHIC Patients –attended one of the UK clinics that contribute data to UKCHIC –were aged 20 years and older –started cART on at least 3 drugs between 1996 and 2008 IDU were excluded Followed up for all cause mortality –Linkage to death registry –Administratively censored on 31 st December 2008 CD4 analysis restricted to the subset of patients who had a measurement in 3 months before start of cART –14868/17661 (84%) patients with CD4

Methods UK CHIC Crude mortality rates were calculated by dividing total no. deaths by total no. years follow up PYLL were calculated as the sum of years patients lost because of premature death before the age of 65 Abridged life tables were constructed from age-specific mortality rates in 5-year bands –These tables describe the mortality experience that hypothetical cohorts of individuals would have had if they were subjected to the mortality rates in the observed calendar periods –The life expectancy at an exact age is the average no. of additional years that will be lived by a person after that age, according to the cross-sectional age- specific mortality rates recorded during the study period

Table 1: Characteristics of patients at cART start UK CHIC (N=5849) (N=3609) (N=4180) (N=4023) 1996 – 2008 (N=17661) Age, median (IQR) 36 (31- 42)36 (32-42)37 (32-43)38 (32-44)37 (32-43) Gender and ethnicity N (%) Male White3856 (66)1703 (47)1965 (47)2077 (52)9601 (54) Male non-White953 (16)845 (23)984 (24)919 (23)3701 (21) Female White229 (3.9)120 (3.3)132 (3.2)116 (2.9)597 (3.4) Female non-White811 (14)941 (26)1099 (26)911 (23)3762 (21) Risk factor for transmission, N (%) MSM3835 (66)1697 (47)2067 (49)2025 (50)9624 (54) Heterosexual1517 (26)1593 (44)1863 (45)1521 (38)6494 (37) Other or unknown497 (8.5)319 (8.8)250 (6.0)477 (11.9)1543 (8.7) CD4 count, median (IQR)140 (50-230)149 (61-225)174 (90-235)200( )166 (75-241) AIDS stage C diagnosis2179 (37)1007 (28)828 (20)576 (14)4590 (26) HIV-1 RNA (log copies/mL) Median (IQR)4.9 ( )5.0 ( )4.9 ( )4.7 ( )4.9 ( ) No previous ART exposure3145 (54)3281 (91)4014 (96)3853 (96)14293 (81)

LE overall and by calendar period UK CHIC

Table 2: Health indicators stratified by period of follow-up UK CHIC Measure Period of Follow-up 1996 — — — — — 2008 Number patientsN=5471N=8493N=12029 N=15152 N=17661 Mortality rates (per 1000 pyears) Overall 26.8 (23.7 – 30.1) 16.3 ( ) 12.2 (11.0 – 13.6) 9.5 ( ) 13.7 (12.9 – 14.5) Between the ages 20 and 44 years 22.7 ( ) 14.5 (12.7 – 16.7) 10.0 (8.6 – 11.5) 7.5 (6.4 – 8.8) 11.7 (10.9 – 12.6) Mortality rates are deaths per 1000 person-years (95% CI). SeStandard error for the estimated life expectancy

Table 2: Health indicators stratified by period of follow-up UK CHIC Measure Period of Follow-up 1996 — — — — — 2008 Number patientsN=5471N=8493N=12029 N=15152 N=17661 Mortality rates (per 1000 pyears) Overall 26.8 (23.7 – 30.1) 16.3 ( ) 12.2 (11.0 – 13.6) 9.5 ( ) 13.7 (12.9 – 14.5) Between the ages 20 and 44 years 22.7 ( ) 14.5 (12.7 – 16.7) 10.0 (8.6 – 11.5) 7.5 (6.4 – 8.8) 11.7 (10.9 – 12.6) Potential years of life lost before age 65 years (per 1000 pyears) 20 to 64 years Mortality rates are deaths per 1000 person-years (95% CI). SeStandard error for the estimated life expectancy

Table 2: Health indicators stratified by period of follow-up UK CHIC Measure Period of Follow-up 1996 — — — — — 2008 Number patientsN=5471N=8493N=12029 N=15152 N=17661 Mortality rates (per 1000 pyears) Overall 26.8 (23.7 – 30.1) 16.3 ( ) 12.2 (11.0 – 13.6) 9.5 ( ) 13.7 (12.9 – 14.5) Between the ages 20 and 44 years 22.7 ( ) 14.5 (12.7 – 16.7) 10.0 (8.6 – 11.5) 7.5 (6.4 – 8.8) 11.7 (10.9 – 12.6) Potential years of life lost before age 65 years (per 1000 pyears) 20 to 64 years Life expectancy (years;adjusted) At exact age 20 years (Se)30.0 (1.2)39.4 (1.2)43.1 (1.0)45.8 (1.7)41.1 (0.5) At exact age 35 years (Se)20.0 (0.6)28.2 (0.6)31.6 (0.5)35.6 (0.5)30.8 (0.2) Mortality rates are deaths per 1000 person-years (95% CI). SeStandard error for the estimated life expectancy

Table 2: Health indicators stratified by period of follow-up UK CHIC Measure Period of Follow-up 1996 — — — — — 2008 Number patientsN=5471N=8493N=12029 N=15152 N=17661 Mortality rates (per 1000 pyears) Overall 26.8 (23.7 – 30.1) 16.3 ( ) 12.2 (11.0 – 13.6) 9.5 ( ) 13.7 (12.9 – 14.5) Between the ages 20 and 44 years 22.7 ( ) 14.5 (12.7 – 16.7) 10.0 (8.6 – 11.5) 7.5 (6.4 – 8.8) 11.7 (10.9 – 12.6) Potential years of life lost before age 65 years (per 1000 pyears) 20 to 64 years Life expectancy (years;adjusted) At exact age 20 years (Se)30.0 (1.2)39.4 (1.2)43.1 (1.0)45.8 (1.7)41.1 (0.5) At exact age 35 years (Se)20.0 (0.6)28.2 (0.6)31.6 (0.5)35.6 (0.5)30.8 (0.2) Percent surviving from 20 to 44 years60.8%74.7%81.6%82.3%77.3% Mortality rates are deaths per 1000 person-years (95% CI). SeStandard error for the estimated life expectancy

Table 3: Health indicators stratified by gender and ethnicity UK CHIC Measure Category White Males Non-White Males Number patientsN=9601N=3701 Mortality rates (per 1000 pyears) Overall 14.9 ( ) 14.9 (13.2 – 16.9) Between the ages 20 and 44 years 12.2 ( ) 14.1 (12.1 – 16.4) Potential years of life lost before age 65 years (per 1000 pyears) 20 to 64 years Life expectancy (years;adjusted) At exact age 20 years (Se)39.2 (1.2)40.3 (1.7) At exact age 35 years (Se)30.0 (0.3)30.6 (0.7) Percent surviving from 20 to 44 years74.7%74.1%

Table 3: Health indicators stratified by gender and ethnicity UK CHIC Measure Category White Males Non-White Males White Females Non-White Females Number patientsN=9601N=3701N=597N=3762 Mortality rates (per 1000 pyears) Overall 14.9 ( ) 14.9 (13.2 – 16.9) 11.0 (7.8 – 15.3) 10.4 (9.0 – 12.0) Between the ages 20 and 44 years 12.2 ( ) 14.1 (12.1 – 16.4) 10.6 (7.1 – 15.7) 9.6 (8.1 – 11.4) Potential years of life lost before age 65 years (per 1000 pyears) 20 to 64 years Life expectancy (years;adjusted) At exact age 20 years (Se)39.2 (1.2)40.3 (1.7)50.8 (3.4)47.0 (1.3) At exact age 35 years (Se)30.0 (0.3)30.6 (0.7)39.8 (2.5)35.1 (1.1) Percent surviving from 20 to 44 years74.7%74.1%80.0%82.4%

Table 4: Health indicators stratified by CD4 count UK CHIC Measure CD4 cell count < 100 cells/mm cells/mm cells/mm 3 Number patientsN=4585N=4434N=5849 Mortality rates (per 1000 pyears) Overall21.0 ( ) 12.1 ( ) 8.0 ( ) Between the ages 20 and 44 years19.1 ( ) 9.3 ( ) 6.6 ( ) Potential years of life lost before age 65 years (per 1000 pyears) 20 to 64 years Life expectancy (years;adjusted) At exact age 20 years (Se)34.9 (1.3) 41.0 (1.6) 51.7 (1.2) At exact age 35 years (Se)26.1 (0.44) 40.6 (0.5) 39.8 (0.7) Percent surviving from 20 to 44 years66.8% 79.9% 86.4% CD4 cell count at start of cART (N=14868).

Table 5: Health indicators stratified by year of starting cART UK CHIC Have not estimated for as fup too short Measure Year of starting cART Number patientsN=5849N=3609N=4180 Mortality rates (per 1000 pyears) Overall15.9 ( ) 10.9 ( ) 10.0 ( ) Between the ages 20 and 44 years14.2 ( ) 9.0 ( ) 7.8 ( ) Potential years of life lost before age 65 years (per 1000 pyears) 20 to 64 years Life expectancy (years;adjusted) At exact age 20 years (Se)39.5 (0.99) 45.2 (0.7) 45.4 (0.8) At exact age 35 years (Se)30.0 (0.32) 32.5 (0.7) 32.4 (0.8) Percent surviving from 20 to 44 years73.5% 84.8% 86.7%

Summary of results UK CHIC The average LE at age 20 over the study period was 41 years –43 years in those who survived first 6 months after starting cART LE improved from 30 to 46 years between and –31 to 47 years in those who survived at least 6 months from start of cART –LE higher in ART-CC analysis which was restricted to naïve patients As in the background population, females have better LE than males by 7 years or more There is no difference in LE between white and non-white males –Very few white females 67%, 80% and 86% of patients aged 20 who start cART with CD4<100, , respectively survive to age 44

Limitations UK CHIC Only 13 years of cART follow up from 1996 –LE is extrapolating outside the range of the data using cross-sectional data Only 2% of patients were aged 60 years and over –Very imprecise mortality estimates in the age group that should have the highest mortality –Adjusted mortality rates in the highest age group using trends across younger ages and information on rates in the UK population Less than 4% of patients were white women so estimates for this group are imprecise Changes in LE over time might reflect changes in demographics (eg increase in proportion of women) as well as improvements in drugs/care

Conclusion UK CHIC Individuals treated for HIV infection in the UK can expect to live many years after starting cART, depending on their age/sex/CD4 count The average LE of HIV infected individuals remains less than in the background UK population (to be quantified), but there has been substantial improvement since 1996 Differences in LE between men and women partially reflect those in the background population, but may also be due to earlier diagnosis and treatment or better adherence and response to treatment in women The impact of HIV infection on PYLL could be reduced by initiating treatment at higher CD4 counts

Acknowledgements UK CHIC is funded by the Medical Research Council, UK (Grant number G ) Loveleen Bansi for data management Caroline Sabin, Mark Gompels for suggestions on analyses

Table 6: Health indicators stratified by period of follow up for patients who survived first 6 months of cART UK CHIC Only 196 deaths in 1 st 6 months, but 756 lost to fup or with fup shorter than 6 months. Measure Period of Follow-up 1996 — — — — — 2008 Number patientsN=4820N=7801N=11205 N=14225 N=16276 Mortality rates (per 1000 pyears) Overall 26.1 (22.7 – 30.0) 15.3 ( ) 11.2 (10.0 – 12.6) 9.0 ( ) 12.6 (11.9 – 13.4) Between the ages 20 and 44 years 22.1 ( ) 14.0 (12.1 – 16.2) 9.1 (7.8 – 10.6) 6.9 (5.8 – 8.1) 10.8 (10.0 – 11.7) Potential years of life lost before age 65 years (per 1000 pyears) 20 to 64 years Life expectancy (years;adjusted) At exact age 20 years (Se)31.2 (1.2)42.2 (1.2)44.6 (1.0)47.0 (1.9)42.9 (0.5) At exact age 35 years (Se)20.5 (0.7)30.8 (0.8)32.6 (0.5)36.4 (0.5)32.0 (0.2) Percent surviving from 20 to 44 years63.8%76.6%83.7%84.0%79.8%