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

Michael Carter
Published: 24 August 2012

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.

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.”

Reference

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.

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