HIV death rates have declined dramatically since the availability HAART and effective prophylaxis for opportunistic infections. Given increasing antiretroviral-related complications and resistance, however, whether this decrease in deaths will be sustained is debated.

Some studies continue to describe high rates of death attributable to AIDS-defining conditions. A relatively recent study found that most deaths occurred among patients with a CD4 count of <200 cells/mL and that a leading cause of death remained Pneumocystis carinii (jiroveci) pneumonia (PCP) [MK Jain et al. Clin Inf Dis 36. 2003].

Other studies have shown an increasing proportion of deaths attributable to non-HIV-related conditions, especially to liver failure. In some cohorts, liver disease now accounts for greater than 50% of the deaths among patients with a CD4 count >200 cells/mL or an undetectable HIV viral load.

Divergent results regarding the cause of death are likely related to the underlying characteristics of the study populations, including injectible drug use, coinfection with hepatitis B and C, medication adherence, and the availability of antiretrovirals. In addition, patients with private insurance have been shown to receive more intensive drug regimens and to have lower mortality rates.

A study among patients with open access to medical care as well as a low rate of drug use and hepatitis C coinfection may provide some insight regarding the effects of these barriers on overall mortality. Researchers at several US military medical centers (primarily naval hospitals) evaluated such a population, US military beneficiaries, to assess causes of death and mortality rates in this cohort during the years 1990 through 2003.

Data collected during this HIV natural history study were retrospectively analyzed for causes of death and annual death rates. The investigators compared death-related variables during the 3 eras.

Results

The number of deaths declined over the study period, with 987 deaths in the pre-HAART era, 159 deaths in the early HAART era (1997-1999), and 78 deaths in the late HAART era (2000-2003) (P < 0.01).

The annual death rate peaked in 1995 (10.3 per 100 patients) and then declined to <2 deaths per 100 persons in the late HAART era (P < 0.01).

The proportion of deaths attributable to infection decreased, but infection remained the leading cause of death in this cohort, followed by cancer.

Of those who died, there was an increasing proportion of non-HIV-related deaths (32% vs. 9%; P < 0.01), including cardiac disease (22% vs. 8%; P < 0.01) and trauma (8% vs. 2%; P = 0.01) in the post-HAART versus pre-HAART era.

Despite the absence of intravenous drug use and the low prevalence of hepatitis C coinfection in our cohort, an increasing proportion of deaths in the HAART era were attributable to liver disease, although the numbers are small.

In closing, the authors write, “Despite increasing concerns regarding antiretroviral resistance, the death rate among HIV-infected persons in our cohort continues to decline. Our data show a lower death rate than that reported among many other US HIV-infected populations; this may be the result of open access to health care.”

“A shift in the causes of death toward non-HIV-related causes suggests that a more comprehensive health care approach may be needed for optimal life expectancy; this may include enhanced screening for malignancy and heart disease as well as preventive measures for liver disease and accidents.”

Discussion

These data show that deaths from HIV infection declined in this cohort similar to the trend seen across the United States since the introduction of HAART. With improvement in HIV treatment, proportionally fewer patients are currently dying of the typical HIV-related illnesses.

AIDS-defining causes of death declined to 56%, whereas non-HIV-related conditions have increased to 32% of the causes of deaths in this cohort. This is similar to other studies, which have shown that AIDS-defining illnesses as a cause of death are rapidly falling.

Deaths during the post-HAART versus pre-HAART era are proportionally more often attributable to cardiac disease, trauma, and liver disease. The authors of the present study also noted increasing cholesterol levels in the post-HAART era; this finding may be related to the introduction of protease inhibitor therapy and may be an important factor in the increasing rate of cardiac disease. Other studies have also noted an increased number of deaths attributable to non-HIV-related diseases, including liver disease, drug overdose, non-AIDS-defining malignancy, cardiac disease, obstructive lung disease, suicide, homicide, and trauma.

This cohort study is ongoing.

01/17/06

Reference
N Crum and others. Comparisons of Causes of Death and Mortality Rates among HIV-Infected Persons: Analysis of the Pre-, Early, and Late HAART (Highly Active Antiretroviral Therapy) Eras. Journal of Acquired Immune Deficiency Syndromes 41(2):194-200, February 1, 2006.

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