Finding Links Between HIV Medicines and Diabetes

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Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, by Stephane De Wit and colleagues. Diabetes Care 31:1224—1229, 2008

What is the problem and what is known about it so far?

Combination antiretroviral therapy (cART) drugs have significantly reduced death and disease from HIV and its complications. However, impaired glucose tolerance, diabetes, and cholesterol disorders have increased among people with HIV, leading to an increase in heart disease, as well.

Why did researchers do this particular study?

The researchers wanted to find out how common new cases of diabetes are among HIV patients and to identify characteristics and factors that might contribute to the development of diabetes in people with HIV.

Who was studied?

More than 33,000 HIV-infected patients followed at 212 clinics in Europe, the United States, Argentina, and Australia were included in this large study of heart disease risk among HIV patients.

How was the study done?

Researchers statistically analyzed data on the patients to find relationships between the development of diabetes and exposure to cART medications after taking other factors into account.

What did the researchers find?

The longer patients received cART drugs, the more likely they were to develop diabetes. The HIV drug stavudine had the strongest link to diabetes, but exposure to the drugs zidovudine and didanosine also resulted in a higher risk for diabetes. The HIV drugs ritonavir and nevirapine were associated with reduced risk for diabetes. Cholesterol levels were linked to the development of diabetes, as well. Lipodystrophy, or loss of body fat, which is common among those on cART medicines, is known to be linked to diabetes in HIV patients; however, even after taking lipodystrophy into account, the link between the cART drugs and diabetes remained. This suggests that the drugs also contribute directly to insulin resistance.

What were the limitations of the study?

The study design allowed researchers to find links between various factors and diabetes but did not allow them to identify causes for those links. The study could not take into account factors such as interruptions in treatment or changes in patients' adherence to their drug regimens. Finally, the study relied only on presence or absence of lipodystrophy, rather than on the degree of lipodystrophy in each patient. Researchers could not tell whether the extent of body fat loss, rather than the mere presence of any body fat loss at all, influenced the development of diabetes.

What are the implications of the study?

Some components of HIV cART treatment—notably stavudine, but also zidovudine and didanosine—are independently linked to the development of diabetes in HIV-infected patients. In addition to causing body fat loss, these drugs may directly contribute to insulin resistance. This information may help guide HIV treatment decisions for people with other risk factors for diabetes and heart disease.

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