Glucose metabolism worsens in HIV treatment-experienced taking NRTI-sparing regimens

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Italian investigators have found evidence of worsening glucose tolerance in highly treatment-experienced HIV-positive patients treated with nucleoside-sparing regimens. The small study, which is published in the online edition of AIDS, monitored the glucose metabolism of 39 patients over three years.

“The drugs included in these regimens have not been specifically associated with worsening of glucose metabolism,” note the authors.

The patients were treated with two alternative combinations: raltegravir (Isentress), etravirine (Intelence) plus maraviroc (Celsentri); or raltegravir, etravirine with ritonavir-boosted darunavir (Prezista). A total of fifteen patients (39%) were treated with the maraviroc-containing regimen and 61% received the darunavir/ritonavir-based therapy. All were highly treatment experienced and were switched to these regimens because of virological failure.



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.


A hormone produced by the pancreas that helps regulate the amount of sugar (glucose) in the blood.


The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.


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 person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

The patients had normal fasting glucose levels (below 110 mg/dl) when they switched therapy. Fasting glucose and insulin levels were monitored every three months over three years of treatment. Impaired glucose tolerance was defined as a glucose level above 140 mg/dl, and diabetes as a basal glucose level of 126 mg/dl or a two-hour post-load level of 200 mg/dl.

The patients had an average age of 48 and 84% were men. They had extensive experience of treatment, the average duration being 16 years. All achieved an undetectable viral load after switching treatment, which was also associated with robust increase in CD4 cell counts.

After 156 weeks of treatment, fasting glucose levels had increased significantly (overall, p = 0.002; maraviroc-based treatment, p = 0.007; darunavir/ritonavir-containing therapy, p = 0.029).

Insulin levels had also decreased in the darunavir/ritonavir group (p = 0.027).

Impaired glucose tolerance was observed in three patients (8%) and diabetes was diagnosed in five (13%), four of whom were taking maraviroc.

The investigators were surprised by this finding as maraviroc has been “postulated to have a protective effect on at least type-1 DM.”

Older age was the only significant risk factor for the development of impaired glucose tolerance or diabetes (p = 0.003).

However, the investigators also noted there was a significant relationship between increases in CD4 cell count and fasting insulin levels at week 156 (p = 0.018). There was also a relationship which bordered on significance between increase in waist circumference and the development of insulin resistance (p = 0.051).

They therefore conclude that the worsening glucose metabolism observed in their patients “may be a consequence of both antiretroviral drugs and restoration of health.”


Bigoloni A et al. Long-term glucose tolerance in highly experienced HIV-infected patients receiving nucleoside analogue-sparing regimens. AIDS, online edition. DOI: 10.1097/QAD.0b013e32835705dd, 2012.