HCV coinfection and PI use increase risk of hyperglycaemia in HIV patients

Michael Carter
Estimated reading time 4 minutes
This article is more than 21 years old.

HIV-positive patients coinfected with hepatitis C virus and treated with a protease inhibitor as part of their HAART regimen are at increased risk of hyperglycaemia, according to a retrospective study conducted by investigators at Johns Hopkins University involving over 1,200 patients and published in the August 15th edition of the Journal of Acquired Immune Deficiency Syndromes.

Hepatitis C has been independently associated with diabetes in many studies, however, the role of hepatitis C infection in the development of hyperglycemia and diabetes in HIV coinfected patients receiving HAART has received little attention. Therefore, investigators at the Johns Hopkins University designed a study to establish the prevalence and incidence of hyperglycemia amongst HIV patients, looking for a possible role for hepatitis C coinfection and possible differences between protease inhibitor (PI) or NNRTI-based HAART.

The study involved 1230 individuals who started their first HAART regimen between January 1996 and May 2002. Hepatitis C coinfection was present in 53% of patients. At baseline, there were no significant differences between HCV-coinfected and uninfected individuals in the prevalence of hepatitis B infection, baseline CD4 cell count, HIV viral load, or glucose levels. Coinfected patients did however, tend to be older, African-American, with a history of injecting drug use, and have abnormal liver function.

Glossary

hyperglycaemia

An excess of glucose (sugar) in the bloodstream. It may occur in a variety of diseases, including diabetes, due to insufficient insulin in the blood and excessive intake of carbohydrates.

glucose

A simple form of sugar found in the bloodstream. All sugars and starches are converted into glucose before they are absorbed. Cells use glucose as a source of energy. People with a constant high glucose level might have a disease called diabetes.

diabetes

A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

HAART was based on a protease inhibitor for 69% of patients, an NNRTI for 22% and both a protease inhibitor and NNRTI for 9% of individuals. At baseline, glucose levels were lower in patients treated with protease inhibitors than those taking other regimens.

Hyperglycaemia was diagnosed if a patient had a glucose level above 200mg/dL at baseline or two random tests during the study above this level. A total of 54 patients had hyperglycemia at baseline (4.47%), of which 36 had a diagnosis of diabetes.

The prevalence of hyperglycaemia was significantly higher in patients coinfected with hepatitis C (5.9%) than those without hepatitis C infection (3.3%, p=0.02).

Patients with hyperglycemia at baseline were excluded from further analysis. In the remaining 1128 HAART-treated patients, new-onset hyperglycaemia was observed in a total of 47 individuals, an incidence of 3.5 per 100 patient years of follow-up (95% CI, 2.6 – 4.6). Thirty-seven of these patients also had diabetes.

In addition, 37 of the patients with new-onset hyperglycaemia were coinfected with hepatitis C and the incidence of hyperglycaemia was 4.9 per 100 patient years of follow-up (95% CI, 3.4 – 7.1) compared to 2.3 per 100 years in individuals uninfected with hepatitis C (95% CI, 1.4 – 3.7).

Individuals taking a protease inhibitor were significantly more likely to be diagnosed with incident hyperglycaemia, with an incidence rate of 4.1 per 100 years (95% CI, 3.0 –5.6) compared to 1.5 per 100 years (95% CI, 0.6 – 4.1) for patients an NNRTI and 2.8 per 100 years (95% CI, 1.0 – 7.4) for those taking both a protease inhibitor and NNRTI.

Accounting for independent risk factors for hyperglycaemia, including age and baseline glucose, strengthened the relationship between hepatitis C coinfection (risk hazard 5.02, 95% CI 1.39 – 8.16) and treatment with a protease inhibitor (RH 2.28, 95% CI 1.23 – 4.22). The investigators note that only one case of hyperglycaemia occurred in a patient who was neither hepatitis C-infected nor taking a protease inhibitor.

The US investigators conclude, “we observed an increased prevalence and incidence of hyperglycemia among HIV-infected adults with HCV coinfection compared to those without infection. PI use also appeared to increase the risk of hyperglycemia compared with persons receiving NNRT-containing HAART regimens.”

Further information on this website

Body fat and metabolic changes whilst on treatment - menu of information

Hepatitis C - overview

Lipodystrophy - factsheets

Hepatitis - factsheets

HIV and hepatitis - booklet in the information for HIV-positive people series (pdf)

Lipodystrophy - booklet in the information for HIV-positive people series (pdf)

References

Mehta SH et al. The effect of HAART on HCV infection on the development of hyperglycemia among HIV-infected persons. JAIDS 33: 577 – 584, 2003.

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