CATIE News

16 October 2012 

Cancers, liver failure and other problems now leading causes of death in Swiss HIV study

The hallmark of AIDS is an array of life-threatening infections and cancers. Fortunately, with the arrival of potent combination anti-HIV therapy (commonly called ART or HAART) in most high-income countries in 1996, deaths due to AIDS-related causes began to decline. Since that time, AIDS-related deaths have generally fallen even lower and have now stabilized. However, deaths continue to occur among HIV-positive people for several possible reasons, including the following:

  • Some HIV-positive people delay seeking care and treatment until they are seriously ill. As a result, treatment may fail to repair their immune system.
  • HIV treatment only partially reduces inflammation associated with this chronic infection.
  • Co-infection with certain viruses causes complications, including cancers. These viruses include the following: hepatitis B and C; human papilloma virus (HPV), and members of the herpes virus family such as EBV (Epstein Barr Virus) and HHV-8 (human herpes virus-8).
  • Prolonged use of street drugs.
  • Lack of access to care and treatment.
  • Obesity.
  • Insufficient exercise.

Different types of studies

Most clinical trials for testing new or reformulated HIV medicines tend to be relatively small and of relatively short duration. Moreover, such trials (usually of a randomized, controlled design) tend to enroll relatively healthy people who have minimal pre-existing conditions. As a result, deaths in such trials, particularly in the past decade, tend to be uncommon.

In many high-income countries, large numbers of HIV-positive people have been enrolled in studies of a different design—observational, or cohort, studies. Such studies, with their large and diverse populations and prolonged duration of monitoring, can provide a better overall picture of the health of HIV-positive people.

The Swiss HIV Cohort Study (SHCS) has been keeping track of the cause of deaths of participants since 1988. In 1999 and again in 2005 Swiss researchers further refined its data collection and analysis, expanding its ability to classify possible causes of death.

In recently reviewing their data, Swiss researchers confirmed a pattern in the cause of death that is being seen across high-income countries. In the time before HAART, deaths were usually due to complications arising from AIDS-related infections and cancers. In the present era (2005 to 2010) AIDS-related deaths have greatly decreased, accounting for 16% of deaths. In contrast, causes unrelated to AIDS now account for 84% of deaths in HIV-positive people These causes of death were as follows:

  • cancers unrelated to AIDS (including liver cancer)
  • liver failure
  • infections unrelated to AIDS
  • complications arising from substance use
  • suicide
  • heart attacks

These findings underscore the need to focus future care initiatives on helping HIV-positive people maintain and improve their overall health and quality of life. Such initiatives could include the following:

  • early initiation of ART
  • help for coping with and recovery from addictions
  • support to overcome mental health issues
  • screening for pre-cancer and cancer
  • monitoring and treatment for hepatitis B and C viral infections
  • vaccinations against hepatitis B virus and HPV
  • support and encouragement for quitting smoking and practicing safer sex
  • advice about changes to the diet and making exercise a part of daily life

Study details

In addition to monitoring participants via the Swiss HIV Cohort Study, the researchers used software developed by Statistics Canada to link the SHCS database with that of the Swiss National Cohort to capture any data that might have been initially missing concerning cause of death.

Results

Starting in 1988, the SHCS amassed a huge trove of data collected from 16,134 HIV-positive people. Between 1988 and 2010, 5,023 of these people died.

The modern era

Focusing on the period from 2005 to 2010, a total of 459 HIV-positive members of the SHCS died. The average profile of these people at their time of death was as follows:

  • 74% men, 26% women
  • age – 47 years
  • duration of HIV infection – 14 years
  • ART was used by 93% of participants
  • CD4+ count – 251 cells
  • active HCV infection – 45%
  • active HBV infection – 11%
  • 36% had a history of injecting street drugs

Causes of death in the modern era

Major causes of death were as follows:

  • non-AIDS-related cancers (including liver cancer) – 19%
  • AIDS-related causes – 16%
  • liver failure (excluding cases of liver cancer) – 15%
  • non-AIDS-related infections – 9%
  • complications from substance use – 7%
  • suicide – 6%
  • heart attack – 6%

Focus on suicide

Generally, men and women died from similar causes. One major exception was suicide: The overall rate in the modern era was 6%, but when broken down by gender, suicide was responsible for 8% of deaths in men and 3% in women.

It is noteworthy that in the pre-ART era the overall suicide rate was about 3% but rose up to 6% in the modern era. This doubling of the suicide rate underscores the need for more vigilance in screening and treating depression.

CD4+ cell counts

Although the majority of deaths occurred in people with 499 or less CD4+ cells, 20% of deaths occurred in people who had 500 or more CD4+ cells.

Hepatitis co-infection

Common causes of death among people co-infected with hepatitis-causing viruses included the following:

  • liver failure (including liver cancer) – 32%
  • non-AIDS-related infections – 14%
  • complications arising from substance use – 11%

Overall

Taking many factors into account, the following were linked to an increased risk of death among the 459 people who died:

  • injecting street drugs
  • being over the age of 40
  • having a low CD4+ cell count (less than 200 cells)
  • smoking tobacco
  • having type 2 diabetes
  • being underweight
  • having untreated HBV or HCV
  • a history of a heart attack
  • interrupting ART

The results of the Swiss study are important because they document the shifting causes of death among people with HIV over the past 20 years. Such shifts are being seen to varying degrees across high-income countries—such as Canada, Denmark, France and the U.S.—and the Swiss study may be a harbinger of the future for some HIV-positive people if additional steps are not taken.

ART has tremendously improved the chances of survival among HIV-positive people, with some studies predicting near-normal life expectancies. However, if the survival benefit of ART is to be extended, then causes of death mentioned in the Swiss study need to be addressed. Medical and psychosocial interventions are necessary to improve the health of HIV-positive people, particularly those co-infected with HBV and HCV infections, some of whom are also struggling with addiction and mental and emotional health issues. Metabolic complications such as pre-diabetes and type 2 diabetes and cardiovascular disease risks also need to be addressed.

Resources:

                                                                                                                       

—Sean R. Hosein

REFERENCES:

  1. Weber R, Ruppik M, Rickenbach M, et al. Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study. HIV Medicine. 2012; in press.
  2. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Annals of Internal Medicine. 2007 Jan 16;146(2):87-95.
  3. Lohse N, Gerstoft J, Kronborg G, et al. Comorbidity acquired before HIV diagnosis and mortality in persons infected and uninfected with HIV: a Danish population-based cohort study. Journal of Acquired Immune Deficiency Syndromes. 2011 Aug 1;57(4):334-9.
  4. Ly KN, Xing J, Klevens RM, et al. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Annals of Internal Medicine. 2012 Feb 21;156(4):271-8.
  5. Lohse N, Hansen AB, Gerstoft J, et al. Improved survival in HIV-infected persons: consequences and perspectives. Journal of Antimicrobial Chemotherapy. 2007 Sep;60(3):461-3.
  6. Klein M, Rollet K, Saeed S, et al. HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality. HIV Medicine. 2012; in press.
  7. Rosenthal E, Salmon-Céron D, Lewden C, et al. Liver-related deaths in HIV-infected patients between 1995 and 2005 in the French GERMIVIC Joint Study Group Network (Mortavic 2005 study in collaboration with the Mortalité 2005 survey, ANRS EN19). HIV Medicine. 2009 May;10(5):282-9.