Risk of diabetes increased by being HIV-positive and on HAART

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HIV-positive men who are taking highly active antiretroviral therapy (HAART) are more than four times more likely to develop diabetes than HIV-negative men, according to an analysis of data from the Multicenter AIDS Cohort Study (MACS). These findings were published in the 23rd May edition of the Archives of Internal Medicine.

Diabetes mellitus is a disease caused by a reduction in the body’s ability to control blood sugar levels. Although it has been associated with HAART for many years, few studies have set out to measure the development of diabetes in people taking HAART. In addition, they have not used measurements of blood sugar levels after fasting to diagnose diabetes, as recommended by the American Diabetes Association.

Investigators from the MACS wished to find out what proportion of men in their cohort had diabetes at the start of the study, and how many went on to develop the condition during follow-up. MACS is a large study that enrolled 5622 gay and bisexual men between 1984 and 1991 in four sites across the United States. Men in the study undergo six-monthly interviews, physical examination and collection of biological specimens, including blood samples for HIV testing and measurements of glucose levels.



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.


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.

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.


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.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

“We found greater than a fourfold increase in the rate of incident diabetes mellitus in HIV-infected participants receiving HAART compared with HIV-seronegative participants,” they conclude. “The four-year risk of 10% is higher than previous estimates and supports the importance of regular screening for hyperglycaemia among HIV-infected persons.

“These findings support and extend previously observed increases in both prevalent and incident fasting hyperglycaemia and diabetes mellitus among HIV-infected patients receiving HAART,” they write.

At the start of the diabetes study in April 1999, 1278 men had baseline measurements of glucose levels taken after a fast of at least eight hours. Fifty-seven (14%) of the 411 HIV-positive men taking HAART had diabetes. Diabetes was diagnosed by a glucose concentration of 126mg/dl (7mM) or higher, or if the participant told the investigators that he was diabetic or using anti-diabetes medicines.

In contrast, 33 (5%) of the 711 HIV-negative men were diabetic. After adjustment of these values for age and for body mass index (BMI), this corresponded to a 4.6-fold greater prevalence of diabetes in the HIV-positive men who were taking HAART (95% confidence interval [CI]: 3.0 – 7.1).

There were only 157 HIV-positive men not taking HAART included in this study. Although they showed a greater prevalence of diabetes than the HIV-negative men (adjusted prevalence ratio = 2.21; 95% CI: 1.12 – 4.31), "the small size of this group precluded a thorough analysis,” say the researchers.

The investigators also examined the ‘incidence’, or number of new cases of diabetes over the four years of the study. They included the 680 men who had a fasting glucose concentration of 98mg/dl (5.4mM) or less at baseline, and who did not report being diabetic or taking anti-diabetes medication.

Over a median follow-up of 2.3 years, there were 4.7 new cases of diabetes per 100 person-years in the HIV-positive men who were using HAART. In contrast, there were 1.4 incident cases per 100 person-years in the HIV-negative group. After adjustment for age and BMI, this was equivalent to a 4.1-fold greater incidence in the HIV-positive HAART-taking group (95% CI: 1.85 – 9.16).

To assess the effect of protease inhibitors, the investigators examined the development of diabetes or ‘hyperglycaemia’ (glucose levels above 100mg/dl [5.5mM]) among the 229 patients taking HAART at the start of the study. They compared the incidence between patients taking the four most commonly used protease inhibitors: ritonavir (Norvir), nelfinavir (Viracept), saquinavir (Invirase / Fortovase) and indinavir (Crixivan).

After adjusting for age, BMI, lowest-ever CD4 cell count and use of nucleoside analogues (NRTIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs), they found that only ritonavir was significantly associated with an increased risk of either diabetes or raised blood glucose (rate ratio [RR] = 1.70; 95% CI: 1.08 – 2.68).

However, they warn: “Because 94% of men in our study who were receiving ritonavir therapy were also receiving at least one other protease inhibitor, it is unclear if the effect is due to ritonavir per se or the combination of protease inhibitors.”

They also carried out an analysis of the effect of lowest-ever CD4 cell count, finding a greater incidence of diabetes or hyperglycaemia in patients whose lowest CD4 cell count was under 300 cells/mm3 (RR = 1.67; 95% CI: 1.00 – 2.80, adjusted for age, BMI and duration of HAART).

The researchers point out that their study is limited by being unable to take two glucose measurements on subsequent days, as recommended for diagnosis of diabetes by the American Diabetes Association. In addition, they acknowledge that using self-reports of diabetes diagnosis may have affected the reliability of their findings, as may the presence of co-infection with hepatitis C, a factor that they are investigating in current studies.


Brown TT et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the Multicenter AIDS Cohort Study. Arch Intern Med 165: 1179-1184, 2005.