Long-term prognosis and time trends Life expectancy - MRC CTU by hedongchenchen

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									   Life expectancy of patients
   treated with ART in the UK:
         UK CHIC Study

                       Margaret May
University of Bristol, Department of Social Medicine, Bristol
                                                                 UKCHIC
Background

• 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): 293-9
• 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
                                                           UKCHIC
Aims

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
                                                                          UKCHIC
Aims

To estimate these health indicators overall and by:

   – Period of follow up
       • 1996-1999, 2000-2002, 2003-2005, 2006-2008
   – Gender and ethnicity
       • White males, non-white males, white females, non-white females
   – CD4 cell count at start of cART
       • <100, 100-199, 200-350 cellscells/mm3
   – Year of starting cART
       • 1996-1999, 2000-2002, 2003-2005


To estimate these health indicators in those who survive
  at least 6 months from start of cART
                                                              UKCHIC
Patients included in analysis

• 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 31st 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
                                                                              UKCHIC
Methods

• 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                                                                 UKCHIC




                                   1996 - 1999     2000 - 2002     2003 - 2005     2006 - 2008     1996 – 2008
                                    (N=5849)        (N=3609)        (N=4180)        (N=4023)        (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 White                     3856 (66)       1703 (47)       1965 (47)       2077 (52)       9601 (54)

     Male non-White                  953 (16)        845 (23)        984 (24)        919 (23)       3701 (21)

     Female White                    229 (3.9)      120 (3.3)       132 (3.2)        116 (2.9)      597 (3.4)

     Female non-White                811 (14)        941 (26)       1099 (26)        911 (23)       3762 (21)

    Risk factor for transmission, N (%)

     MSM                            3835 (66)       1697 (47)       2067 (49)       2025 (50)       9624 (54)

     Heterosexual                   1517 (26)       1593 (44)       1863 (45)       1521 (38)       6494 (37)

     Other or unknown                497 (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(113-263)    166 (75-241)

    AIDS stage C diagnosis          2179 (37)       1007 (28)        828 (20)        576 (14)       4590 (26)
    HIV-1 RNA (log copies/mL)
    Median (IQR)                   4.9 (4.1-5.4)   5.0 (4.3-5.5)   4.9 (4.2-5.4)   4.7 (4.0-5.2)   4.9 (4.1-5.4)

    No previous ART exposure        3145 (54)       3281 (91)       4014 (96)       3853 (96)      14293 (81)
LE overall and by calendar period   UKCHIC
Mortality rates are deaths per 1000 person-years (95% CI).
Se             Standard error for the estimated life expectancy
         Table 2: Health indicators stratified by period of follow-up                                                     UKCHIC




                                                                                  Period of Follow-up
       Measure
                                              1996 — 1999         2000 — 2002        2003 — 2005        2006 — 2008   1996 — 2008
       Number patients                           N=5471             N=8493             N=12029           N=15152        N=17661

       Mortality rates (per 1000
       pyears)
                                                  26.8                16.3               12.2               9.5           13.7
       Overall                                (23.7 – 30.1)       (14.6 -18.3)       (11.0 – 13.6)      (8.6 -10.6)   (12.9 – 14.5)
       Between the ages 20 and 44                 22.7                14.5                10.0              7.5           11.7
       years                                   (19.5-26.2)        (12.7 – 16.7)       (8.6 – 11.5)      (6.4 – 8.8)   (10.9 – 12.6)
Mortality rates are deaths per 1000 person-years (95% CI).
Se             Standard error for the estimated life expectancy
         Table 2: Health indicators stratified by period of follow-up                                                     UKCHIC




                                                                                  Period of Follow-up
       Measure
                                              1996 — 1999         2000 — 2002        2003 — 2005        2006 — 2008   1996 — 2008
       Number patients                           N=5471             N=8493             N=12029           N=15152        N=17661

       Mortality rates (per 1000
       pyears)
                                                  26.8                16.3               12.2               9.5           13.7
       Overall                                (23.7 – 30.1)       (14.6 -18.3)       (11.0 – 13.6)      (8.6 -10.6)   (12.9 – 14.5)
       Between the ages 20 and 44                 22.7                14.5                10.0              7.5           11.7
       years                                   (19.5-26.2)        (12.7 – 16.7)       (8.6 – 11.5)      (6.4 – 8.8)   (10.9 – 12.6)

       Potential years of life lost
       before age 65 years (per 1000
       pyears)
       20 to 64 years                             611.3              365.5              248.5             175.1          285.3
Mortality rates are deaths per 1000 person-years (95% CI).
Se             Standard error for the estimated life expectancy
         Table 2: Health indicators stratified by period of follow-up                                                     UKCHIC




                                                                                  Period of Follow-up
       Measure
                                              1996 — 1999         2000 — 2002        2003 — 2005        2006 — 2008   1996 — 2008
       Number patients                           N=5471             N=8493             N=12029           N=15152        N=17661

       Mortality rates (per 1000
       pyears)
                                                  26.8                16.3               12.2               9.5           13.7
       Overall                                (23.7 – 30.1)       (14.6 -18.3)       (11.0 – 13.6)      (8.6 -10.6)   (12.9 – 14.5)
       Between the ages 20 and 44                 22.7                14.5                10.0              7.5           11.7
       years                                   (19.5-26.2)        (12.7 – 16.7)       (8.6 – 11.5)      (6.4 – 8.8)   (10.9 – 12.6)

       Potential years of life lost
       before age 65 years (per 1000
       pyears)
       20 to 64 years                             611.3              365.5               248.5            175.1          285.3

       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).
Se             Standard error for the estimated life expectancy
         Table 2: Health indicators stratified by period of follow-up                                                     UKCHIC




                                                                                  Period of Follow-up
       Measure
                                              1996 — 1999         2000 — 2002        2003 — 2005        2006 — 2008   1996 — 2008
       Number patients                           N=5471             N=8493             N=12029           N=15152        N=17661

       Mortality rates (per 1000
       pyears)
                                                  26.8                16.3               12.2               9.5           13.7
       Overall                                (23.7 – 30.1)       (14.6 -18.3)       (11.0 – 13.6)      (8.6 -10.6)   (12.9 – 14.5)
       Between the ages 20 and 44                 22.7                14.5                10.0              7.5           11.7
       years                                   (19.5-26.2)        (12.7 – 16.7)       (8.6 – 11.5)      (6.4 – 8.8)   (10.9 – 12.6)

       Potential years of life lost
       before age 65 years (per 1000
       pyears)
       20 to 64 years                             611.3              365.5               248.5            175.1          285.3

       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 years                                   60.8%              74.7%              81.6%             82.3%          77.3%
Table 3: Health indicators stratified by gender and ethnicity          UKCHIC




                                                 Category
Measure
                                                        Non-White
                                      White Males
                                                          Males
Number patients                         N=9601           N=3701

Mortality rates (per 1000 pyears)
                                          14.9             14.9
Overall                               (13.9-16.0)      (13.2 – 16.9)
                                          12.2             14.1
Between the ages 20 and 44 years      (11.1 -13.5)     (12.1 – 16.4)

Potential years of life lost before
age 65 years (per 1000 pyears)
20 to 64 years                           291.4              332.7

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
years                                   74.7%               74.1%
Table 3: Health indicators stratified by gender and ethnicity                                   UKCHIC




                                                                   Category
Measure
                                                     Non-White                            Non-White
                                      White Males                      White Females
                                                       Males                              Females
Number patients                         N=9601        N=3701                  N=597       N=3762

Mortality rates (per 1000 pyears)
                                          14.9           14.9                 11.0           10.4
Overall                               (13.9-16.0)    (13.2 – 16.9)        (7.8 – 15.3)   (9.0 – 12.0)
                                          12.2           14.1         10.6                    9.6
Between the ages 20 and 44 years      (11.1 -13.5)   (12.1 – 16.4)    (7.1 – 15.7)       (8.1 – 11.4)

Potential years of life lost before
age 65 years (per 1000 pyears)
20 to 64 years                           291.4          332.7                 247.3         252.4

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
years                                   74.7%           74.1%                 80.0%        82.4%
Table 4: Health indicators stratified by CD4 count                                          UKCHIC




                                                              CD4 cell count
Measure
                                          < 100 cells/mm3    100-199 cells/mm3   200-350 cells/mm3
Number patients                                  N=4585           N=4434              N=5849

Mortality rates (per 1000 pyears)
Overall                                   21.0 (19.4-22.9)    12.1 (10.8-13.6)     8.0 (7.0-9.2)
Between the ages 20 and 44 years          19.1 (17.2-21.2)    9.3 (7.9-11.0)       6.6 (5.5-7.8)

Potential years of life lost before age
65 years (per 1000 pyears)
20 to 64 years                                   452.5             238.6              160.3

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 years            66.8%             79.9%              86.4%



    CD4 cell count at start of cART (N=14868).
Table 5: Health indicators stratified by year of starting cART                               UKCHIC




                                                             Year of starting cART
Measure
                                            1996-1999             2000-2002          2003-2005
Number patients                               N=5849                N=3609             N=4180

Mortality rates (per 1000 pyears)
Overall                                   15.9 (14.9-17.1)      10.9 (9.5-12.4)      10.0 (8.5-11.7)
Between the ages 20 and 44 years          14.2 (12.9-15.5)      9.0 (7.6-10.6)       7.8 (6.3-9.6)

Potential years of life lost before age
65 years (per 1000 pyears)
20 to 64 years                                 333.3                 221.0              203.1

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 years         73.5%                  84.8%              86.7%



    Have not estimated for 2005-2008 as fup too short
                                                                            UKCHIC
Summary of results

• 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 1996-99 and 2006-08
   – 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, 100-199, 200-350 respectively survive to age 44
                                                                              UKCHIC
Limitations

• 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
                                                                 UKCHIC
Conclusion

• 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 G0000199)

Loveleen Bansi for data management

Caroline Sabin, Mark Gompels for suggestions on
analyses
 Table 6: Health indicators stratified by period of follow up
                                                                                                          UKCHIC
 for patients who survived first 6 months of cART

                                                                Period of Follow-up
Measure
                               1996 — 1999      2000 — 2002        2003 — 2005        2006 — 2008   1996 — 2008
Number patients                   N=4820          N=7801             N=11205           N=14225        N=16276

Mortality rates (per 1000
pyears)
                                    26.1            15.3                11.2              9.0           12.6
Overall                         (22.7 – 30.0)    (13.6-17.3)       (10.0 – 12.6)      (8.1-10.1)    (11.9 – 13.4)
Between the ages 20 and 44          22.1            14.0                 9.1              6.9           10.8
years                            (18.6-26.3)    (12.1 – 16.2)       (7.8 – 10.6)      (5.8 – 8.1)   (10.0 – 11.7)

Potential years of life lost
before age 65 years (per
1000 pyears)
20 to 64 years                     588.3           348.8               226.3            161.5          259.9

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 years                           63.8%           76.6%              83.7%             84.0%          79.8%



   Only 196 deaths in 1st 6 months, but 756 lost to fup or with fup shorter than 6 months.

								
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