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      Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study

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          Abstract

          Objectives To estimate life expectancy for people with HIV undergoing treatment compared with life expectancy in the general population and to assess the impact on life expectancy of late treatment, defined as CD4 count <200 cells/mm 3 at start of antiretroviral therapy.

          Design Cohort study.

          Setting Outpatient HIV clinics throughout the United Kingdom.

          Population Adult patients from the UK Collaborative HIV Cohort (UK CHIC) Study with CD4 count ≤350 cells/mm 3 at start of antiretroviral therapy in 1996-2008.

          Main outcome measures Life expectancy at the exact age of 20 (the average additional years that will be lived by a person after age 20), according to the cross sectional age specific mortality rates during the study period.

          Results 1248 of 17 661 eligible patients died during 91 203 person years’ follow-up. Life expectancy (standard error) at exact age 20 increased from 30.0 (1.2) to 45.8 (1.7) years from 1996-9 to 2006-8. Life expectancy was 39.5 (0.45) for male patients and 50.2 (0.45) years for female patients compared with 57.8 and 61.6 years for men and women in the general population (1996-2006). Starting antiretroviral therapy later than guidelines suggest resulted in up to 15 years’ loss of life: at age 20, life expectancy was 37.9 (1.3), 41.0 (2.2), and 53.4 (1.2) years in those starting antiretroviral therapy with CD4 count <100, 100-199, and 200-350 cells/mm 3, respectively.

          Conclusions Life expectancy in people treated for HIV infection has increased by over 15 years during 1996-2008, but is still about 13 years less than that of the UK population. The higher life expectancy in women is magnified in those with HIV. Earlier diagnosis and subsequent timely treatment with antiretroviral therapy might increase life expectancy.

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          Most cited references34

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          Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies.

          Jonathan Sterne (2008)
          Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, and stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude mortality rates were also calculated. 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, respectively. 2056 (4.7%) deaths were observed during the study period, with crude mortality rates decreasing from 16.3 deaths per 1000 person-years in 1996-99 to 10.0 deaths per 1000 person-years in 2003-05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36.1 (SE 0.6) years to 49.4 (0.5) years. Women had higher life expectancies than did men. Patients with presumed transmission via injecting drug use had lower life expectancies than did those from other transmission groups (32.6 [1.1] years vs 44.7 [0.3] years in 2003-05). Life expectancy was lower in patients with lower baseline CD4 cell counts than in those with higher baseline counts (32.4 [1.1] years for CD4 cell counts below 100 cells per muL vs 50.4 [0.4] years for counts of 200 cells per muL or more). Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability between subgroups of patients. The average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries.
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            Changes in the risk of death after HIV seroconversion compared with mortality in the general population.

            Krishnan Bhaskaran, Osamah Hamouda, Mette Sannes … (2008)
            Mortality among human immunodeficiency virus (HIV)-infected individuals has decreased dramatically in countries with good access to treatment and may now be close to mortality in the general uninfected population. To evaluate changes in the mortality gap between HIV-infected individuals and the general uninfected population. Mortality following HIV seroconversion in a large multinational collaboration of HIV seroconverter cohorts (CASCADE) was compared with expected mortality, calculated by applying general population death rates matched on demographic factors. A Poisson-based model adjusted for duration of infection was constructed to assess changes over calendar time in the excess mortality among HIV-infected individuals. Data pooled in September 2007 were analyzed in March 2008, covering years at risk 1981-2006. Excess mortality among HIV-infected individuals compared with that of the general uninfected population. Of 16,534 individuals with median duration of follow-up of 6.3 years (range, 1 day to 23.8 years), 2571 died, compared with 235 deaths expected in an equivalent general population cohort. The excess mortality rate (per 1000 person-years) decreased from 40.8 (95% confidence interval [CI], 38.5-43.0; 1275.9 excess deaths in 31,302 person-years) before the introduction of highly active antiretroviral therapy (pre-1996) to 6.1 (95% CI, 4.8-7.4; 89.6 excess deaths in 14,703 person-years) in 2004-2006 (adjusted excess hazard ratio, 0.05 [95% CI, 0.03-0.09] for 2004-2006 vs pre-1996). By 2004-2006, no excess mortality was observed in the first 5 years following HIV seroconversion among those infected sexually, though a cumulative excess probability of death remained over the longer term (4.8% [95% CI, 2.5%-8.6%] in the first 10 years among those aged 15-24 years). Mortality rates for HIV-infected persons have become much closer to general mortality rates since the introduction of highly active antiretroviral therapy. In industrialized countries, persons infected sexually with HIV now appear to experience mortality rates similar to those of the general population in the first 5 years following infection, though a mortality excess remains as duration of HIV infection lengthens.
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              Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group.

              J. Bruun, S Vella, P. Gargalianos … (1998)
              The introduction of combination antiretroviral therapy and protease inhibitors has led to reports of falling mortality rates among people infected with HIV-1. We examined the change in these mortality rates of HIV-1-infected patients across Europe during 1994-98, and assessed the extent to which changes can be explained by the use of new therapeutic regimens. We analysed data from EuroSIDA, which is a prospective, observational, European, multicentre cohort of 4270 HIV-1-infected patients. We compared death rates in each 6 month period from September, 1994, to March, 1998. By March, 1998, 1215 patients had died. The mortality rate from March to September, 1995, was 23.3 deaths per 100 person-years of follow-up (95% CI 20.6-26.0), and fell to 4.1 per 100 person-years of follow-up (2.3-5.9) between September, 1997, and March, 1998. From March to September, 1997, the death rate was 65.4 per 100 person-years of follow-up for those on no treatment, 7.5 per 100 person-years of follow-up for patients on dual therapy, and 3.4 per 100 person-years of follow-up for patients on triple-combination therapy. Compared with patients who were followed up from September, 1994, to March, 1995, patients seen between September, 1997, and March, 1998, had a relative hazard of death of 0.16 (0.08-0.32), which rose to 0.90 (0.50-1.64) after adjustment for treatment. Death rates across Europe among patients infected with HIV-1 have been falling since September, 1995, and at the beginning of 1998 were less than a fifth of their previous level. A large proportion of the reduction in mortality could be explained by new treatments or combinations of treatments.
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                Author and article information

                Contributors
                : Role: senior research fellow
                : Role: consultant physician, director
                : Role: consultant epidemiologist, head of HIV and AIDS reporting section
                : Role: senior epidemiologist, Role: honorary reader
                : Role: clinical senior lecturer in HIV medicine
                : Role: professor and consultant physician of general medicine, HIV/AIDS, and thoracic medicine
                : Role: biostatistician
                : Role: consultant in genitourinary medicine
                : Role: consultant physician and senior clinical lecturer
                : Role: professor of medicine and director of HIV clinical research
                : Role: research fellow
                : Role: consultant in HIV and sexual health
                : Role: consultant physician in HIV and genitourinary medicine
                : Role: consultant HIV physician
                : Role: consultant HIV physician
                : Role: research statistician
                : Role: professor of epidemiology
                : Role: honorary professor of medicine, consultant physician in infectious diseases
                : Role: consultant physician, Role: senior lecturer
                : Role: consultant physician, director of the centre for the study of sexual health and HIV
                : Role: professor of medical statistics and epidemiology
                Journal
                Journal ID (nlm-ta): BMJ
                Journal ID (publisher-id): bmj
                Title: BMJ : British Medical Journal
                Publisher: BMJ Publishing Group Ltd.
                ISSN (Print): 0959-8138
                ISSN (Electronic): 1468-5833
                Publication date Collection: 2011
                Publication date (Print): 2011
                Publication date (Electronic): 11 October 2011
                Volume: 343
                Electronic Location Identifier: d6016
                Affiliations
                [1 ]School of Social and Community Medicine, Bristol University, Bristol BS8 2PS, UK
                [2 ]HIV Service, North Bristol NHS Trust, Bristol
                [3 ]HIV and STI Department, Health Protection Services, Health Protection Agency, London
                [4 ]Medical Research Council Clinical Trials Unit, London
                [5 ]University College London, London
                [6 ]King’s College London, London
                [7 ]Royal Free Hospital NHS Trust, London
                [8 ]Leicester Royal Infirmary, Leicester
                [9 ]UCL Centre for Sexual Health and HIV Research, Mortimer Market Centre,  London
                [10 ]Chelsea and Westminster Hospital, London.
                [11 ]Imperial College Healthcare Trust, London
                [12 ]Brighton and Sussex University Hospitals, Brighton
                [13 ]Barts and The London School of Medicine and Dentistry, London
                [14 ]North Middlesex University Hospital, London
                [15 ]Western General Hospital, Edinburgh
                [16 ]Imperial College School of medicine, London
                [17 ]Homerton University Hospital NHS Foundation, London
                Author notes
                Correspondence to: M May m.t.may@ 123456bristol.ac.uk
                Article
                Publisher ID: maym857151
                DOI: 10.1136/bmj.d6016
                PMC ID: 3191202
                PubMed ID: 21990260
                SO-VID: 7ee82879-7138-4613-ab62-566f928b1b5d
                Copyright © © May et al 2011
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                Date accepted : 24 August 2011
                Categories
                Subject: Research
                Subject: Infectious Diseases
                Subject: Epidemiologic Studies
                Subject: Immunology (Including Allergy)
                Subject: Sexual Health

                ScienceOpen disciplines: Medicine
                Data availability:
                ScienceOpen disciplines: Medicine

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