Cause of Serious Illness Among HAART Users Not Clear

Highly active antiretroviral therapy (HAART) has dramatically decreased AIDS-related deaths in North America and Western Europe. Despite this benefit, some people with HIV/AIDS (PHAs) in these regions can still develop serious complications. It is therefore important that long-term monitoring of HAART users be conducted to find out the following:

• the causes of serious illness in this population
• ways of predicting the onset of complications
• ways of preventing these problems

One team of researchers at the National Institutes of Health (NIH) and elsewhere in the United States have begun this work and we report on their results.

Study Details

Researchers collected data from 3,227 HIV positive subjects who participated in several clinical trials between the years 1996 and 2001. They had the following profile:

• 16% female, 84% male
• average CD4+ count: 241 cells
• 37% had AIDS before entering the NIH study
• 46% had previously not used anti-HIV drugs
• at least 22% had hepatitis B and/or C viruses

On average, subjects were monitored for about 1½ years and they received HAART once they enrolled in a clinical trial.

Results -- Defining the problem

The NIH researchers analysed their data, in part, by collecting information on the number of "AIDS-related events" such as AIDS-related infections. They also collected data on serious or life-threatening complications (which they called "grade IV events"). These complications included such events as bone marrow damage, inflamed pancreas glands, liver-related problems and so on. In analysing their data, here is what the researchers found that occurred over the course of their study:

• number of AIDS-related events: 316
• number of grade IV events: 663

As a proportion of the study population, the figures can be expressed as follows:

• AIDS-related events: 14%
• grade IV events: 28%

Thus, grade IV events were twice as common as AIDS-related illnesses.

Survival

After about 30 months, about 10% of subjects died. The risk of death from AIDS or a grade IV event was about equal. This attests to the severity of such complications. Although PHAs who had more than 200 CD4+ cells had a relatively low risk of developing AIDS (6%), their risk of developing a grade IV event was about four times greater (26%).

Which Grade IV Events Occurred

The most common grade IV event was complications from liver disease, related to hepatitis virus infection. Other common problems included:

• bone marrow damage
• painfully swollen pancreas glands (pancreatitis)
• "psychiatric" difficulties
• cardiovascular complications
• kidney-related problems

Unfortunately, researchers were unable to find out the cause(s) of the grade IV events reported. Indeed, it is important to remember that many factors can play a role in the development of grade IV events, including the following:

• stage of HIV disease
• co-infections and other pre-existing problems
• drug interactions
• toxicity of anti-HIV drugs and other medications
• poor nutrition
• substance use (including alcohol and recreational drugs)
• a person's genetic background

Researchers were also unable to make a link between specific HAART regimens and grade IV events.

This large American study points to the need for conducting more carefully designed long-term studies of anti-HIV therapies to help find out how different therapies affect survival and the development of serious complications (grade IV events). This would better clarify the risks and benefits of specific anti-HIV therapies.

Reference

1. Reisler R., Han C., Burman W., et al. Incidence of grade IV events, AIDS and mortality in a large multicenter cohort receiving HAART. Abstract 36.