Despite dramatic falls in death rates since the introduction of highly active antiretroviral therapy (HAART), infection and cancer remain the most common causes of death in HIV-positive patients, according to a large study from the United States. The findings were published in the 1st February edition of The Journal of Acquired Immune Deficiency Syndromes.
The study also showed that mortality is shifting towards causes of death not directly related to HIV, including heart disease, trauma and liver disease, as HIV treatments improve.
It is well established that death rates have fallen since the introduction of HAART in 1996. However, many experts are concerned about the impact of complications associated with HIV treatment and drug resistance on HIV-positive patients. To find out more information on changing landscape of mortality, investigators from the Triservice AIDS Clinical Consortium analysed death rates and causes of death among over 4240 HIV-positive military beneficiaries between 1990 and 2003.
As expected, the investigators found that annual death rates fell after the introduction of HAART. Between 1990 and 1996, there were 987 deaths, with death rates peaking at 10.3% in 1995. They then fell steadily from 1996, to a rate of 0.2% in 2003 (p
Overall, death rates fell by 80% between 1990 and 2003, with the median survival time after seroconversion increasing from eight to twelve years.
The proportion of deaths caused by infection fell across the whole study period, from 59% between 1990 and 1996 to 38% between 1997 and 1999 and 24% between 2000 and 2003 (p
Cancer was the second commonest cause of death, with the proportion of deaths from cancer rising from 20% between 1990 and 1996 to 26% in the early HAART period between 1997 and 1999. The proportion of deaths attributable to cancer fell to 12% between 2000 and 2003, but these changes did not reach statistical significance.
The researchers categorised the deaths according to whether they were AIDS-related, HIV-related or not related to HIV. AIDS-associated deaths were those caused by a ‘category C’ disease listed by the Centers for Disease Control and Prevention, while HIV-related deaths were caused by a disease related to immunodeficiency.
Deaths from AIDS-defining conditions fell from 80% before 1996 to 65% in the early HAART era and 56% between 2000 and 2003 (p
The increase in non-HIV-related deaths included elevations in the rates of heart disease (8 vs. 22%; p
The proportion of patients dying from hepatitis B or C also increased, despite the prevalence of both diseases being very low in the cohort. One per cent of the deaths was caused by hepatitis B before the introduction of HAART, compared to 4% thereafter (p = 0.04). Similarly, deaths from hepatitis C rose from less than 1% to 4% after HAART was introduced (p = 0.01).
“With improvements in HIV treatment, proportionally fewer patients are currently dying of the ‘typical’ HIV-related illnesses,” the investigators conclude. “Of those who die, the causes are increasingly attributable to cardiac disease, trauma and liver disease.
“We also noted increasing cholesterol levels in the post-HAART era,” they continue. “This finding may be related to the induction of protease inhibitor therapy and may be an important factor in the increasing rate of cardiac disease.”
The study’s authors admit that their findings differ from other similar studies, some of which have found very high rates of death through liver disease. This may be explained by their study population, which has a low rate of drug use and hepatitis C co-infection, open access to medical care and free HIV medication.
Crum NF et al. Comparisons of causes of death and mortality rates among HIV-infected patients. Analysis of the pre-, early, and late HAART (highly active antiretroviral therapy) eras. J Acquir Immune Defic Syndr 41: 194 - 200, 2006.