North American study links anemia to reduced survival among people with HIV

• A North American study assessed health-related information from over 67,000 people with HIV
• People with anemia (low hemoglobin levels in the blood) had an increased risk of death
• Researchers encourage screening patients for anemia and investigating the cause when found

Capturing oxygen

The body has an iron-containing protein called hemoglobin. This protein attaches to oxygen absorbed from the lungs and transports oxygen to tissues. Hemoglobin then absorbs the waste product carbon dioxide to the lungs, where it is exhaled. Without enough oxygen, organs do not function properly and can become injured. People may also feel tired more easily. These problems can occur if insufficient levels of hemoglobin are present—a condition called anemia. Prolonged anemia can be a signal that a person’s health is deteriorating.

Before effective HIV treatment (antiretroviral therapy; ART) became widely available, anemia was a relatively common problem in people with HIV. As there was no effective treatment for HIV in that era, anemia could become worse, degrading quality of life and health. At that time, anemia was linked to reduced life expectancy in people with HIV.

In North America

Since 1996, the widespread availability of ART has led to a dramatic decrease in deaths due to AIDS in North America and other regions. The power of ART is so tremendous that research increasingly indicates that many ART users will have near-normal life expectancy.

Recently, a team of researchers in Canada and the U.S. analyzed health-related information from more than 67,000 people with HIV. They focused on anemia and its relationship to survival to understand if anemia is still an issue in the 21^st century among people with HIV.

The researchers analysed data collected between the years 2007 and 2016. Overall, they found that increased severity of anemia was linked to an increased risk for death. Men with anemia seemed to have a greater risk of dying than women with anemia. What’s more, anemia could occur as early as four years prior to a person’s subsequent death in the study.

Study details

Researchers analysed data from 67,228 people with HIV, all of whom were prescribed and using ART. The average profile of participants upon study entry was as follows:

• 88% men; 12% women
• age – 51 years
• major ethno-racial groups – 46% White, 41% Black
• CD4+ count – 517 cells/mm³; 11% of participants had 200 or fewer CD4+ cells/mm³
• most participants had a suppressed viral load (less than 50 copies/mL)
• leading comorbidities included: high blood pressure – 40%; hepatitis C virus – 19%; type 2 diabetes – 14%; chronic kidney disease – 10%
• history of AIDS – 25%

 On average, participants were in the study for nearly four years. 

Results

Overall, 80% of participants did not have anemia. The distribution of different grades of anemia among the remaining participants was as follows:

• mild anemia – 14%
• moderate anemia – 6%
• severe anemia – 0.2%

Age, gender and comorbidities

Researchers found that anemia was less common in younger people compared to older people, as follows:

• age 18 to 39 – 14%
• age 70 and older – 39%

Women were more likely (31%) to have anemia than men (18%).

The research team stated that “anemia was significantly more common among people with HIV [who had any of the following comorbidities]”:

• hepatitis B or C virus infection
• type 2 diabetes
• high blood pressure
• chronic kidney disease
• a history of an AIDS-related illness

Survival

The researchers found that 5,638 people died during the study. More deaths occurred among people with anemia (74%) than people without anemia (26%). 

They also found that increasing severity of anemia was linked to an increased risk of dying. The following distribution shows the proportion of people with different degrees of anemia who died within the same year that anemia was diagnosed:   

• mild anemia – 3% died
• moderate anemia – 14% died
• severe anemia – 28% died

Anemia over several years

Researchers found that people who eventually died in the study had declining levels of hemoglobin within four years of their death. Men had a significantly greater decline in hemoglobin levels than women. 

The greater the severity of anemia, the greater the risk of death. The researchers stated that the risk of death increased as follows:

Men

• mild anemia – a 4-fold increased risk of death
• moderate anemia – a 15-fold increased risk of death
• severe anemia – a 38-fold increased risk of death

Women

• mild anemia – a 2-fold increased risk of death
• moderate anemia – a 7-fold increased risk of death
• severe anemia – a 16-fold increased risk of death

Bear in mind

The researchers found that anemia and increasing severity of anemia is linked to decreased survival. Hemoglobin is measured in grams per decilitre (g/dL). The researchers stated that for every 1 g/dL decline in the average annual hemoglobin level, the risk of death increased significantly. 

There was no relationship between changes in HIV viral load and the development of anemia.

The researchers stated that “younger women likely have a higher prevalence of anemia because of blood loss through menses, typically leading to iron deficiency, which decreases following menopause. By contrast, anemia among men is not related to [any monthly cycle] but instead likely reflects an underlying issue.”

The source of anemia in participants was not noted and the research team did not have information on the cause of death. They also lacked information on the following issues, which they stated could have played a role in the development of anemia and death:

• drug use
• excessive use of alcohol
• socio-economic status
• traumatic events
• diet and nutrition

These issues are important. ART can largely help heal the body from immunologic injury caused by HIV. However, it cannot address other issues, such as those mentioned above.

As anemia was associated with an increased cause of death in the study, the research team stated that a diagnosis of anemia “should prompt clinicians to investigate the underlying cause, especially if the anemia is moderate/severe or [becomes worse].” In addition, they suggest that regular screening for anemia is an important part of health monitoring for people with HIV. Should anemia be diagnosed, the researchers encourage clinicians to investigate its possible cause.

—Sean R. Hosein

REFERENCE:

Lang R, Coburn SB, Gill MJ, et al. The association of anemia with survival among people with HIV following antiretroviral initiation in the NA-ACCORD 2007 to 2016. JAIDS. 2024;97(4):334-343.