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Comorbidities & Life Expectancy: the affect of comorbidities on Life Expectancy
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Download the PDF here
Download the PDF here
from Jules:"Expanded service delivery interventions to address complex care needs of ageing PLHIV are crucial to address shorter life expectancies, and improve their healthy states.".....This study is from British Columbia where they look at the affect of comorbidities on life expectancy in HIV+; this is an unusual stuy, perhaps one of the few if any that looks at how comorbidities decrease may decrease life expectancy in HIV+. They found a higher rate of renal & liver disease in HIV+ and find a surprisingly shorter life expectancy in HIV+ vs HIV- saying the higher comorbidity rate is the cause and say "these results expose the toll of comorbidities on the life expectancy of PLHIV."......"reported thathealthy life expectance in PLHIV who had ever used antiretroviral therapy (ART) was 27 years shorter in men and 36 years shorter in women than in their uninfected counterparts.Directly adjusted mortality rates were also substantially higher for PLHIV than for HIV negative individuals: 36⋅5 deaths per 1000 person-years for HIV-infected women versus 5⋅8 deaths per 1000 person-years for HIV-uninfected women"..........In British Columbia IDU is a problem but I think this study reflects the affect of a history of IDU & lifestyle behaviors on the development of comorbidities & life expectancy - the authors say - "We also argue that the substantial differences in health life expectancies could be attributed to previous history of injection drug use among PLHIV....Although the increased burden of liver and renal disease affecting PLHIV in our sample might be caused by current or previous use of injection drugs, these diseases could be mitigated through access to direct-acting antiviral regimens and tenofovir alafenamide-based antiretroviral regimens." - HIV and some of the HIV ARTs contribute to CVD, kidney disease, and liver disease so a history of substance abuse & IDU contribute but so does HIV and perhaps ART. I think this study & the commentary highlight to us (1) that comorbidities are more frequent in HIV which we knew but that this contributes to shortened mortality in HIV+, and this has not been reported in studies as far as I know, and (2) I think the contribution of a history of substance abuse and IDU can contribute to mortality & comorbidities, and (3) the Comment discusses nadir CD4 saying that those that started HAART with low CD4 have increased risk for mortality and this is a major issue. The current group of older aging HIV+ are from the earlier days where HAART was deferred until CD4s were very low - between <100 to 150 very often - and this is likely a strong contributor to the frailty, high comorbidities rates we are seeing in this current older aging HV+ individuals. And the author suggests in Comment that starting ART with high CD4s as we do know can contribute to longer life expectancy & perhaps less comorbidities - this remains to be seen - if comorbidities are also due to HIV & ARTs - inflammation & immune activation - which IS a contributory factor - then, I think yes earlier ART will help but will not resolve the problem. Finally, cure. For this older aging HIV+ person with HIV for 25-30 years the damage to their organs & immune system has been done, a cure might stop the spiral down but perhaps the damage dome already is irreparable, it may not prevent kidney, CVD, or cancer risks, bone disease. As the authors say we need special services for older patients & for their clinics & clinicians including education for clinicians, patients & service providers - "Expanded service delivery interventions to address complex care needs of ageing PLHIV are crucial to address shorter life expectancies, and improve their healthy states."
from original study - see original study below
"We aimed to estimate health-adjusted life expectancy (HALE) among adults living with and without HIV, and examine dependency between causes of comorbidities......Men and women living with HIV had high prevalences of renal and liver diseases compared with those in HIV-negative counterparts......we add to the literature by integrating HALE measures to generate insight into how a substantially higher burden of comorbidity can directly affect the health life expectancy of PLHIV compared with their HIV-negative counterparts.....At exactly age 20 years, HALE was about 31 years (SD 0⋅16) among men living with HIV and 27 years (0⋅16) among women living with HIV. In the HIV-negative population, HALE was around 58 years (SD 0⋅02) for men and 63 years (0⋅02) for women. These results seem independent of ordering. However, PLHIV, particularly women living with HIV, had much shorter overall life expectancies than did their HIV-negative counterparts in the general population [29⋅1 years (SD 0⋅1)vs65⋅4 years (0⋅1)], and thus spent less time in a healthy state."
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COMMENT
Liver disease and healthy life-expectancy with HIV
As HIV infection shifts to become a chronic condition, studies addressing the quantity and quality of the life gained by people living with HIV (PLHIV) are essential. Healthy life expectancy is an health indicator that quantifies and qualifies life expectancy and provides the expected number of years of life lived in good health adjusted by the different morbidity patterns of a population. With this method, a population-based cohort study by Robert Hogg and colleagues1 in The Lancet HIV shows that healthy life expectancy among PLHIV has room for improvement.
The researchers analysed data from 9310 adults HIV-infected and 501 313 HIV-uninfected adults from British Columbia, Canada, and reported thathealthy life expectance in PLHIV who had ever used antiretroviral therapy (ART) was 27 years shorter in men and 36 years shorter in women than in their uninfected counterparts. Directly adjusted mortality rates were also substantially higher for PLHIV than for HIV negative individuals: 36⋅5 deaths per 1000 person-years for HIV-infected women versus 5⋅8 deaths per 1000 person-years for HIV-uninfected women. As for comorbidities, liver diseases were seven times more prevalent among HIV-infected men and renal diseases were five times more prevalent; among women, the relative risk of age-adjusted prevalence was about ten-fold higher in those with HIV for both diseases. Interestingly, the proportion of time lived in a healthy state was similar for the two populations. Together, these results expose the toll of comorbidities on the life expectancy of PLHIV.
HIV-related and non-HIV-related factors contribute to the higher mortality and lower life expectancy for PLHIV than for the general population. Immune status at start of ART is a decisive HIV-related factor, whereas non-HIV related factors include sociodemographics (sex, socioeconomic status) and behaviours (smoking, alcohol use, and illicit drug use) as well as comorbidities.2 A study from the USA showed that HIV-infected individuals who start ART with CD4 counts greater than 350 cells per μL are more likely to die at older ages and of non-AIDS causes than those who start with greater immunological impairment.3 Moreover, if predictors of mortality (CD4 cell count, hepatitis B infection, hepatitis C infection, smoking, depression, unemployment, and hypertension) were adjusted for in the analysis then the hazards of death for the two populations converged.3 Similarly, studies from Brazil4 and Thailand5 show that life expectancy for PLHIV increased with increasing CD4 cell count at the start of ART. Furthermore, the Thai study5 found that life expectancy for HIV-infected individuals with CD4 cell counts greater than 350 cells per μL reached that of the general population.5 In a meta-analysis, life expectancy differed with country's income,6 while in a high-income country (Swiss HIV Cohort Study) life expectancy differed by education level.7 Hence, life expectancy for HIV-infected individuals can, and probably will, reach that of uninfected populations when we address HIV disease progression with early ART as well as social inequalities and behaviours that increase the risk of mortality of HIV-infected individuals.
As for the role of comorbidities in HIV-specific mortality, findings from Hogg and colleagues1 could result from the effect of HIV on the natural history of hepatitis C.8 Compared with patients who are monoinfected with hepatitis C, patients who are coinfected with HIV and hepatitis C have accelerated progression to cirrhosis.9 In the Cohorts of Spanish Network on HIV/AIDS, excess mortality from hepatitis C infection in HIV-infected individuals compared with the general population as measured by standardised mortality ratio (per 100 person-years) were shown for all-cause mortality (11⋅5 [95% CI 9⋅9–13⋅4]vs 2⋅4 [1⋅9–3⋅1]) and liver-related mortality (22⋅4 [14⋅6–34⋅3] vs 1⋅8 [0⋅6–5⋅7]).10 Fortunately, options are currently available to address hepatitis C. New therapeutic regimens (direct-acting antiviral drugs) that target specific hepatitis C genome regions offering increased efficacy (sustained virological response ≥90%) in short duration and simplified oral dosing are available.11 As such, high-coverage of well established prevention strategies coupled with direct-acting antiviral drugs treatment could greatly contribute to decreasing hepatitis C incidence and prevalence.12 Additionally, early ART might reduce rates of liver fibrosis progression in PLHIV regardless of hepatitis B or hepatitis C coinfection.13 Ultimately, reduced hepatitis C coinfection and progression to end-stage liver disease might lead to an improvement in healthy life expectancy of PLHIV.
In sum, the high prevalence of liver disease in PLHIV compared with in HIV-uninfected individuals as well as its effect on healthy life expectancy warrants careful monitoring. In this regard, three strengths of the study by Hogg and colleagues1 (the use of a health indicator that accounts for morbidity and mortality, the population-based nature of the cohorts with health information derived from multiple data sources, and the exploration of the ordering of the diseases on the study's results in sensitivity analyses) set important benchmarks for future studies.
HP declares no competing interests. PML acknowledges funding from the National Council of Technological and Scientific Development and Research Funding Agency of the State of Rio de Janeiro.
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Health-adjusted life expectancy in HIV-positive and HIV-negative men and women in British Columbia, Canada: a population-based observational cohort study
Lancet HIV Hogg et al March 2 2017
"We aimed to estimate health-adjusted life expectancy (HALE) among adults living with and without HIV, and examine dependency between causes of comorbidities......Men and women living with HIV had high prevalences of renal and liver diseases compared with those in HIV-negative counterparts......we add to the literature by integrating HALE measures to generate insight into how a substantially higher burden of comorbidity can directly affect the health life expectancy of PLHIV compared with their HIV-negative counterparts.....At exactly age 20 years, HALE was about 31 years (SD 0⋅16) among men living with HIV and 27 years (0⋅16) among women living with HIV. In the HIV-negative population, HALE was around 58 years (SD 0⋅02) for men and 63 years (0⋅02) for women. These results seem independent of ordering. However, PLHIV, particularly women living with HIV, had much shorter overall life expectancies than did their HIV-negative counterparts in the general population [29⋅1 years (SD 0⋅1) vs 65⋅4 years (0⋅1)], and thus spent less time in a healthy state."
"we add to the literature by integrating HALE measures to generate insight into how a substantially higher burden of comorbidity can directly affect the health life expectancy of PLHIV compared with their HIV-negative counterparts.".....We aimed to estimate health-adjusted life expectancy (HALE) among adults living with and without HIV, and examine dependency between causes of comorbidities.....At exactly age 20 years, HALE was about 31 years (SD 0⋅16) among men living with HIV and 27 years (0⋅16) among women living with HIV. In the HIV-negative population, HALE was around 58 years (SD 0⋅02) for men and 63 years (0⋅02) for women. These results seem independent of ordering. However, PLHIV, particularly women living with HIV, had much shorter overall life expectancies than did their HIV-negative counterparts in the general population [29⋅1 years (SD 0⋅1) vs 65⋅4 years (0⋅1)], and thus spent less time in a healthy state......Although we noted little differences in the levels of morbidity compression by HIV status, PLHIV-especially women living with HIV-spent less time in a healthy state. Expanded service delivery interventions to address complex care needs of ageing PLHIV are crucial to address shorter life expectancies, and improve their healthy states.
We also argue that the substantial differences in health life expectancies could be attributed to previous history of injection drug use among PLHIV. The effect of liver-related illnesses and hepatitis C on morbidity and mortality rates amon PLHIV who inject drugs or have a history of injection drug use.18, 19, 20 Lesko and colleagues21 reported higher rates of end-stage renal and liver diseases among PLHIV who inject drugs compared with non-injecting PLHIV. Although the increased burden of liver and renal disease affecting PLHIV in our sample might be caused by current or previous use of injection drugs, these diseases could be mitigated through access to direct-acting antiviral regimens and tenofovir alafenamide-based antiretroviral regimens.22
In conclusion, our results show that PLHIV spend proportionally about the same amount of time in a healthy state as their HIV-negative counterparts in British Columbia. However, PLHIV, especially women, have much shorter overall life expectancies than their HIV-negative general population counterparts, and thus spend notably less time in a healthy state. Because life expectancy for many PLHIV is increasingly comparable to HIV-negative populations,22 we show here that it remains imperative to address the challenges this population faces in achieving a healthy state to improve quality of life over the life course.
The primary outcome variable in our analysis was HALE. This measure estimates the number of healthy years an individual is expected to live at birth by subtracting the years of ill health from overall life expectancy.4 In addition to HALE, we estimated the prevalence of five comorbidities, which were used to estimate HALE. Because of their prevalence among PLHIV, we considered cardiovascular, respiratory, liver, and renal diseases, and non-AIDS defining cancers. All comorbidities were predefined, and we used International Classification of Diseases (ICD) 9 and 10 codes and directly standardised to 1991 Canadian population.
49 605 deaths and 5576 841 person-years were accumulated during this study. 21% (1958 of 9310) of PLHIV ever on ART died compared with 9% (47 647 of 510 313) in the uninfected cohort. Life expectancy at exact age 20 years between those ever on ART and those uninfected was 33⋅7 years (SE 0⋅1) versus 60⋅5 years (0⋅1) for men and 29⋅1 years (0⋅1) versus 65⋅4 years (0⋅1) for women. Among PLHIV, women had a significantly lower life expectancy at this exact age than men (29⋅1 years [SE 0⋅1] vs 33⋅7 years [0⋅1]; p<0⋅001).
Rates of mortality, crude and directly adjusted to the Canadian population, were significantly higher among both men and women living with HIV (table 2).
Men and women living with HIV had high prevalences of renal and liver diseases compared with those in HIV-negative counterparts. Among PLHIV with liver disease, hepatitis C accounts for 25% (2024 of 8145) of person-years lived with liver disease in men and 54% (1003 of 1799) of person-years lived with liver disease in women (data now shown). By contrast, among HIV-negative men and women, only 6% (3348 of 53 460) and 5% (2226 of 44 845) of person-years lived due to liver disease can be attributed to hepatitis C (data not shown).
Substantial difference was observed between unadjusted and adjusted HALE measures (table 3, appendix p 3). However, the ordering of comorbidities makes little difference in the estimate of HALE and suggests that the level of contraction is similar by sex and HIV status. Although men and women living with HIV spent a similar proportion of their life in a healthy state, the years lived in this state were much shorter for PLHIV than for their HIV-negative counterparts (table 3, figure). This difference was especially noticeable among women living with HIV.
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