HIV raises the risk of inflammatory bowel disease

People living with HIV have a higher risk of developing inflammatory bowel disease, data from Denmark and the United States show.

The Danish analysis, which looked at the entire population of people living with HIV in Denmark, found an increased risk of inflammatory bowel disease in men living with HIV, but not in women. The US analysis found a raised risk in both men and women living with HIV, with a higher prevalence in women than in men.

The study investigators say that any new gastrointestinal symptoms in people with HIV, such as diarrhoea, pain, blood in stools or weight loss, should prompt consideration of inflammatory bowel disease as the cause.

Background

Inflammatory bowel disease is a term chiefly used to described two conditions, ulcerative colitis and Crohn’s disease. The conditions damage the gut in different places, but the symptoms are similar. Recurring diarrhoea, sometimes with blood, pain and cramping in the abdomen, weight loss and tiredness are the most common symptoms. Inflammatory bowel disease is entirely different from, and far more severe than irritable bowel syndrome.

Symptoms of ulcerative colitis tend to come and go. Management of the condition has improved over the past decade so fewer people need surgery to overcome serious complications.

Crohn’s disease remains a challenging condition for many people. Although Crohn’s disease can go into a period of remission after a flare up, damage to the gut – especially the small bowel – can become increasingly severe. Crohn’s and Colitis UK reports that up to one in five people will need surgery within five years of a diagnosis of Crohn’s disease to remove part of their bowel as a result of damage caused by inflammation.

The causes of these conditions are unclear, although having a close relative with Crohn’s disease increases the risk of the condition. The contributions of the immune system and HIV are also uncertain.

The gut contains large concentrations of immune system cells (lymphoid tissue). CD4 cells in lymphoid tissue are the main target of HIV, so the gut wall forms the main site of the HIV reservoir in the body. What’s unclear is how HIV interacts with tissue in the gut and if the depletion of CD4 cells in the gut by HIV either raises or reduces the risk of inflammatory bowel disease.

The study

To investigate whether people with HIV have a higher risk of inflammatory bowel disease, Danish researchers used the national patient registry to identify all HIV diagnoses and matched each person living with HIV by age and sex at birth with 50 HIV-negative people. They then identified all diagnoses of inflammatory bowel disease (excluding HIV colitis) and calculated the risk of inflammatory bowel disease in people with HIV compared to the control group.

The study identified 8,995 people diagnosed with HIV between 1983 and 2018 and matched them to 449,750 people without HIV. The population living with HIV was 78% male, 69% were born in Denmark, 20% outside Europe and just over ten percent in other European countries. Thirty-five percent had been diagnosed with HIV before the introduction of highly active antiretroviral treatment in 1996 and 62% were under 40 at diagnosis.

During the study follow-up period, 0.82% of people with HIV developed inflammatory bowel disease compared to 0.63% of people without HIV. Ulcerative colitis was the reason for the majority of diagnoses of inflammatory bowel disease in people with HIV (70%). People with HIV were more than twice as likely as people without HIV to develop inflammatory bowel disease (hazard ratio 2.25). Sensitivity analyses designed to rule out bowel disease caused by HIV but misdiagnosed as inflammatory bowel disease resulted in a slightly reduced risk estimate (hazard ratio 1.79).

Inflammatory bowel disease tends to be diagnosed between the ages of 15 and 40 years of age in the general population. In this study population, it was diagnosed at an average age of 45 years in people with HIV compared to 48 years in people without HIV. Among people over the age of 40, people with HIV were almost three times more likely to be diagnosed with inflammatory bowel disease as people without HIV.

"Any new gastrointestinal symptoms in people with HIV, such as diarrhoea, pain, blood in stools or weight loss, should prompt consideration of inflammatory bowel disease as the cause."

Having an immune-mediated inflammatory disorder such as rheumatoid arthritis or lupus did not raise the risk of developing inflammatory bowel disease in people with HIV.

Because the study used the anonymised national patient registry to collect data, the investigators were unable to show if CD4 count at HIV diagnosis affected the risk of being diagnosed with inflammatory bowel disease or if antiretroviral treatment or type of treatment had any effect on the risk of developing the condition.

However, they found no difference in the risk of inflammatory bowel disease between people diagnosed with HIV before 1996 and after 1996 when compared to people without HIV.

The risk of inflammatory bowel disease was higher in men with HIV than the rest of the population (hazard ratio 2.75) but not in women (HR 0.93).

People with HIV born in Denmark were at an increased risk of inflammatory bowel disease compared to people without HIV born in Denmark (HR 2.5) but the same was not true for people with HIV born in other European countries or outside Europe. A previous study found that among immigrants to Denmark, the risk of inflammatory bowel disease increased after living in Denmark for more than twenty years, suggesting that environmental factors such as diet, smoking and reduced physical activity may contribute to the condition.

To validate the findings of the Danish study, the researchers also looked at a US cohort derived from the Explorys database, which contains anonymised electronic heath records from 1999 onwards. In the US cohort, 1610 people had a diagnosis of inflammatory bowel disease recorded in their health record. The risk of diagnosis was 41% higher among people with HIV (HR 1.41) but whereas the Danish cohort found a higher risk in men, the US cohort found a higher risk in women (OR 1.87) than in men with HIV (OR 1.09) (both statistically significant). The US study also found that people with HIV under 30 had a much greater risk of diagnosis. They were six times more likely to be diagnosed compared to people without HIV. The increase was modest in people with HIV over 30 (OR 1.39).