Mortality rates continue to fall in the Swiss HIV cohort

Mortality in people with HIV is continuing to fall, Swiss investigators report in HIV Medicine. The mortality rate in 2010 was a little over 1% and the majority of deaths were due to non-AIDS-related causes, many of which were associated with modifiable risk factors.

“Smoking and other modifiable cardiovascular risk factors, substance abuse, and HCV [hepatitis C virus] co-infection substantially influenced the distribution of causes of death,” write the authors.

They believe that more needs to be done to accurately record causes of death in people with HIV, especially as autopsies are performed in less than a fifth of cases.

The introduction of effective antiretroviral therapy in the mid 1990s was accompanied by a large fall in HIV-related mortality. However, mortality rates are still higher among people living with HIV compared to the general population. Understanding causes of death is of fundamental importance for HIV treatment, care and prevention.

Investigators from the Swiss HIV Cohort Study wanted to establish a better understanding of mortality rates and causes of death in the people in their care. They therefore designed a study involving everyone who received care between 1988 and 2010.

A total of 16,134 people were included in the analysis and 5023 (31%) died.

The investigators examined causes of death in three different time periods: the pre-treatment era (1988-1995); the early antiretroviral era (1996-2004); and the modern treatment era (2005-2010).

In the pre-treatment era, 78% of deaths were attributable to AIDS. This had fallen to 15% by 2005-2010. However, the proportion of deaths due to non-AIDS-related diseases increased from 17 to 71%.

AIDS-related mortality peaked in 1992, at a rate of 11 per 100 person-years. This fell to a rate of just 0.144 deaths per 100 person-years in 2006. Non-AIDS-related mortality also fell from a rate of 1.74 per 100 person-years in 1993 to 0.776 per 100 person-years in 2003. There was a simultaneous decline in mortality rates attributed to unknown causes, from 2.33 per 100 person-years in 1994 to 0.207 per 100 person-years in 2007.

In 2010, the mortality rates for AIDS, non-AIDS-related causes and unknown causes were 0.21, 0.86 and 0.26 per 100 person-years respectively.

The investigators then examined the characteristics of the people who died in the modern HIV treatment era.

A total of 459 people (5%) who received care between 2005 and 2009 died. This provided a mortality rate of 1.25 per 100 person-years. Median age at the time of death was 47 years; the median duration of diagnosed HIV infection was 14 years; 93% of those dying had experience of antiretroviral therapy; and the last median CD4 cell count was 251 cells/mm³. Co-infection with viral hepatitis was highly prevalent.  Some 45% of those dying were co-infected with hepatitis C and 11% were co-infected with hepatitis B.

The most frequent causes of death were non-AIDS-related cancers (19%); AIDS (16%); liver failure (15%); non-AIDS-related infections (9%); substance abuse (7%); suicide (6%); and heart attack (6%).

Between 2005 and 2009, there were significant changes in the characteristics of the people who died. Their median age increased (45 vs 49 years, p < 0.001); their duration of infection with HIV was longer (13 vs 16 years, p = 0.002); their median CD4 cell counts were higher (257 vs 321 cells/mm³, p = 0.005); and the proportion of people who had never taken HIV treatment fell (13 to 5%, p = 0.005).

Causes of death also changed significantly. The proportion dying from AIDS fell from 23 to 9%, whereas the percentage of deaths caused by non-AIDS-related cancers increased from 13 to 24%.

At the time of death, 40% of people in the study had a CD4 cell count below 200 cells/mm³ and 20% had a CD4 cell count above 500 cells/mm³.

Analysis of deaths among people with hepatitis C-co-infection showed that 32% were due to liver failure; 14% were caused by non-AIDS-related infections; 14% were attributed to substance abuse; and 8% were related to non-HIV-related cancers.

Overall, an increased risk of death was associated with injecting drug use, a lower CD4 cell count, smoking, diabetes, low body mass index, active hepatitis B or hepatitis C co-infection and interrupting HIV therapy.

“Many of these causes of death were associated with modifiable risk factors which require increased attention in primary and specialized care,” write the authors.

Only 19% of those dying in the most recent period were autopsied, and the investigators found discrepancies between the causes of death recorded using an HIV-specific coding system and those entered into national death registries. The investigators were concerned by these findings and stressed the importance of accurately establishing the probable cause of death.

Despite this, they were encouraged by their results, concluding: “Mortality in HIV-persons with access to care is continuously decreasing and causes of death are changing.”