The UK CHIC Study included data on 35
377 people with HIV, of whom 22
876 started antiretroviral therapy in 1996-2008. We excluded one patient with missing age and 315 who were aged under 20, 820 (4%) with an assumed risk transmission through use of injected drugs, 3137 (14%) known to have started antiretroviral therapy with a CD4 count above the recommended treatment threshold of 350 cells/mm3
, 743 (3%) with missing ethnicity, and 199 with no follow-up time recorded. This left 17
661 patients eligible for inclusion in the analyses.
Table 1 shows the characteristics of patients at baseline by the period in which they started antiretroviral therapy and overall. The proportions of white people, men, and men who have sex with men were higher in 1996-9 compared with later periods. Compared with later periods, patients who started antiretroviral therapy in 1996-9 were more immunosuppressed and were more likely to have had a diagnosis of AIDS. Patients had a median follow-up of 5.1 (interquartile range 2.2-8.9) years. During the 91
203 person years of follow-up 1248 (7%) patients died.
Characteristics of patients at start of combination antiretroviral therapy (by period of initiation of treatment (n=17 661) (P<0.001 for all variables). Figures are numbers (percentage) of patients unless stated otherwise
Table 2 shows the time trends in health indicators by period of follow-up. Life expectancy at the exact age of 20 increased by nearly 16 years from 1996-9 to 2006-8, and there was a linear trend (P<0.001) across period of follow-up for overall mortality and mortality at age 20-44. For a hypothetical cohort of patients starting antiretroviral therapy at age 20 and experiencing the age specific death rates observed during 1996-9, the proportion surviving to age 45 would have been slightly over 60%. This figure increased to over 80% when we used the death rates experienced from 2003 onwards. During these years there was a corresponding shift in the distribution of measurements of CD4 counts (fig 1). Each measurement was included as an independent observation and assigned to the relevant period of follow-up (the frequency of CD4 monitoring did not change greatly over the study period). In 1996-9, 38% of measurements were <200 cells/mm3 and 34% were >350 cells/mm3, whereas in 2006-8 the proportions were 12% and 65%, respectively.
Health indicators for overall treated population of patients (age ≥20) who started antiretroviral therapy in 1996-2008 by period of follow-up
Fig 1 Distribution of current CD4 count by period of follow-up
Table 3 shows the life expectancy for men and women with HIV undergoing treatment during the study period and, for comparison, the life expectancy of the UK population. Compared with the same sex in the general UK population, for patients undergoing treatment for HIV infection, life expectancy at age 20 was 18.3 years less for men and 11.4 years less for women. Compared with men, the life expectancy of women was greater by just less than four years, but this difference is magnified in those treated for HIV, where the gap was over 10 years.
Health indicators stratified by sex for treated population who started antiretroviral therapy 1996-2008 (n=17 661) and for the UK population (1996-2006)
To show the potential effect of late treatment on life expectancy, we estimated health indicators stratified by CD4 count for patients who had not previously received any antiretroviral drugs and started therapy with three or more drugs after 2000, when non-nucleoside reverse transcriptase inhibitors were widely available. Out of 11
812 patients who started antiretroviral therapy in 2000-8, 664 (6%) were pre-treated with one or two drugs and were not eligible for inclusion. Of the 11
148 eligible patients, 9657 (87%) had a CD4 count recorded at baseline and were included in the analysis. Figure 2 shows life expectancy between the ages of 20 and 65 in those with HIV stratified by CD4 count compared with the life expectancy of men and women in the UK population. Table 4 shows that life expectancy decreased by over 10 years in those starting antiretroviral therapy with CD4 <200 cells/mm3
compared with 200-350 cells/mm3
. The population impact of premature mortality before the age of 65 is illustrated by the difference in potential years of life lost, which increased by a factor of three for patients who started with CD4 <100 cells/mm3
compared with 200-350 cells/mm3
, an absolute difference of 237 years lost per 1000 person years (24%). If we compare this with the UK population estimates shown in table 3, the difference in potential years lost is about 9%, 15%, and 33% for those who start antiretroviral therapy with a CD4 count 200-350, 100-199, and <100 cells/mm3
, respectively. As the life expectancy for the general UK population (weighted by the sex proportion of the HIV positive cohort) is about 58.8 years at the exact age of 20, the loss in life expectancy from the high to low CD4 groups is 5.4, 17.8, and 20.9 years, respectively. Of note, 5895 out of 14
001 (42%) patients in UK CHIC had a CD4 count <200 cells/mm3
within three months of diagnosis.
Fig 2 Life expectancy from age 20-65 of people who started antiretroviral therapy in 2000-8 by CD4 cell count group at start of antiretroviral therapy compared with that of UK population (2000-6 women and men)
Health indicators for patients who had not previously received antiretroviral drugs and started combination antiretroviral therapy in 2000-8 stratified by CD4 cell count at start of treatment (n=9657)
In sensitivity analyses that varied the adjustment to rate of death in the open age group (≥65), the life expectancy at the exact age of 20 varied from 49.8 (no adjustment) to 37.9 for a rate ratio of 6 (maximum adjustment considered). We estimated this life expectancy to be 41.1 years (see table 2), using the observed average rate ratio in the 55-59 and 60-64 groups, which was 2.56. For comparison, life expectancy was 42.7 and 40.3 years with 2 and 3 as plausible limits of the rate ratio adjustment.
We found little evidence of a difference in life expectancy between white and non-white groups once sex had been accounted for, but estimates were imprecise because of imbalances in the distribution of ethnicity by sex and the heterogeneous nature of the non-white group. We also found that restricting analyses to those who survived at least six months after starting antiretroviral therapy improved life expectancy at age 20 (overall for period 1996-2008) by less than two years. We repeated analyses stratifying by period of starting antiretroviral therapy instead of period of follow-up, omitting 2005-8 as there was insufficient follow-up for patients starting treatment in the most recent years. As expected, we found a similar strong trend of improvement in health indicators over the first three calendar periods (see appendix 2 on bmj.com).