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Exploring Factors Linked to Longer Survival Among ART Users

By Sean R. Hosein

January 2014

In the UK, Professor Caroline Sabin, Ph.D., from University College London has been analysing different studies of HIV-positive people and how such studies estimate life expectancy. She has confirmed in a recent analysis that many studies conducted in high-income countries have found a dramatic reduction in AIDS-related deaths among ART users since 1996.


Factors Unrelated to HIV

In drilling deeper into the data, Professor Sabin has found that factors unrelated to HIV can have a major impact on survival in the recent era. Those factors include the following:

Studies have found that some HIV-positive people tend to have higher rates of those factors than HIV-negative people. Furthermore, smoking tobacco can have such a profound impact on survival that it may shorten people's lifespan in ART users more than HIV does.

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One large observational study called ART-CC comprises 70,000 HIV-positive participants from Europe and North America. In one analysis of health-related information, researchers with ART-CC examined data on life expectancy and found that the proportions of ART users with a life expectancy similar to that of HIV-negative people were as follows:

Analysing the data slightly differently, looking for the proportions of participants with the greatest risk of death, researchers found this distribution:

In a Danish study examining clinical events in the period from 1995 to 2008, researchers found that non-AIDS-related causes of death fell significantly among people who did not inject street drugs, while such deaths rose over the same period among IDUs.

These findings confirm the serious effect of injecting drugs -- overdoses, accidents and exposure to germs with major consequences, such as serious bacterial infections and viruses that cause hepatitis which can lead to liver failure and, in some cases, liver cancer.

Professor Sabin also calls attention to another study, done in Alabama, which found that patients who missed clinic appointments in the first year after initiating ART "had over twice the rate of long-term [death] compared with those attending all scheduled appointments. ..."


Factors Related to HIV

Late Diagnosis

Studies in Brazil, Western Europe and North America suggest that a diagnosis late in the course of HIV disease is a factor associated with an increased risk of death. This risk arises because the body and the immune system have been severely weakened.


Getting to 500 Cells With ART

In one European study called COHERE, with more than 80,000 HIV-positive participants, researchers found that the risk of subsequent death fell tremendously among men who achieved a CD4+ count of at least 500 cells after starting ART, approaching the risk seen in HIV-negative men. However, for HIV-positive women, even when they maintained CD4+ counts of 500 cells or more for over five years, the results were not the same. The reasons for this may be that HIV-positive women are more likely than HIV-negative women to smoke tobacco and to have a history of injecting street drugs.

When researchers segregated their analysis of survival among women who were not IDU, then their survival after three years of attaining and maintaining a CD4+ count of 500 cells or more became similar to that of HIV-negative women.

Among IDUs who achieved a CD4+ count of 500 cells, death rates were elevated compared to non-IDU HIV-negative people "even after five years of maintaining a CD4+ count of [at least 500 cells]," the COHERE researchers reported.

The COHERE team also explored survival among older HIV-positive ART users. Among people aged 60 or older who had a CD4+ count of at least 500 cells, both men and women had a risk of death similar to that seen among HIV-negative people. The COHERE researchers explained that this finding was due to at least the following two factors:


Are Neighbourhoods a Factor?

Another study in British Columbia has found that HIV-positive people living in different neighbourhoods have different rates of death. They compared one neighbourhood where there was a relatively high concentration of people who injected street drugs to another neighbourhood with a relatively high concentration of gay men. The researchers said, "We found significant differences between patients from the two neighbourhoods for all socioeconomic variables. Patients in the neighbourhood with a high concentration of injecting drug users were more likely to be female, have a history of injecting drug use, have a less HIV-experienced physician and be less adherent." They also found that even among those who used ART the risk of death for IDUs in that neighbourhood was threefold greater than that of gay men using ART in another neighbourhood.

Making the Right Comparisons

Regardless of HIV infection status, differences in survival by neighbourhood can vary by city, region or even within a country. For instance, Professor Sabin stated that overall male life expectancy at birth in the years 2007 to 2009 was about 84 years in parts of London, compared to 73 years for males who were living in parts of Glasgow. She said that this and other differences in life expectancy among HIV-negative people can be explained by "differences in the characteristics of those living in different regions, particularly socioeconomic status, lifestyle factors and dietary factors." Thus, she argues that when making comparisons between HIV-negative and HIV-positive people, it is probably useful to match each HIV-positive person to an HIV-negative person who has similar "lifestyle and behavioural characteristics ..." so that a more accurate estimation of life expectancy can be obtained.

In one study comparing HIV-positive and HIV-negative people in the U.S. several years ago, researchers found that life expectancy for the average HIV-negative person was about 76 years. When researchers recalculated the life expectancy in their study using HIV-negative people with similar behaviours and characteristics of their HIV-positive population, the average life expectancy of this group of HIV-negative people fell to 68 years. Adjusting estimations of life expectancy -- taking into account alcohol use, tobacco smoking, use of other substances, consequences of sexually transmitted infections (STIs) -- is an important point that needs to be considered. When the U.S. researchers took these factors into account and estimated the life expectancy of their HIV-positive population, they arrived at a figure of about 56 years.


Increasing Life Expectancy for HIV-Positive People

The studies that we have reported on in this issue of TreatmentUpdate suggest that there is still much work to be done raising the life expectancy of key populations who have HIV. Such work needs to be focused on care and treatment issues mainly unrelated to HIV, likely including at least the following themes:

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Until these and other measures become routine across North America for all groups hit hard by HIV, gaps in survival between the different groups mentioned in these and other studies will persist.


References

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  2. Tavernise S. List of smoking-related illnesses grows significantly in U.S. report. New York Times. 17 January, 2014. [Subscription may be required]
  3. Marin B, Thiébaut R, Bucher HC, et al. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy. AIDS. 2009 Aug 24;23(13):1743-53.
  4. Losina E, Schackman BR, Sadownik SN, et al. Racial and sex disparities in life expectancy losses among HIV-infected persons in the United States: Impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy. Clinical Infectious Diseases. 2009 Nov 15;49(10):1570-8.
  5. Helleberg M, Afzal S, Kronborg G, et al. Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study. Clinical Infectious Diseases. 2013 Mar;56(5):727-34.
  6. Lewden C, Chene G, Morlat P, et al. HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population. Journal of Acquired Immune Deficiency Syndromes. 2007 Sep 1;46(1):72-7.
  7. Krentz HB, Kliewer G, Gill MJ. Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada from 1984 to 2003. HIV Medicine. 2005 Mar;6(2):99-106.
  8. Druyts EF, Rachlis BS, Lima VD, et al. Mortality is influenced by locality in a major HIV/AIDS epidemic. HIV Medicine. 2009 May;10(5):274-81.
  9. Cohen MH, French AL, Benning L, et al. Causes of death among women with human immunodeficiency virus infection in the era of combination antiretroviral therapy. American Journal of Medicine. 2002 Aug 1;113(2):91-8.
  10. Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord, et al. All-cause mortality in treated HIV-infected adults with CD4 ≥500/mm3 compared with the general population: evidence from a large European observational cohort collaboration. International Journal of Epidemiology. 2012 Apr;41(2):433-45.
  11. Samji H, Cescon A, Hogg RS, et al. Closing the Gap: Increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One. 2013 Dec 18;8(12):e81355.




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