People with HIV have a poorer response to diabetes therapy

HIV infection is associated with a poorer response to therapy for diabetes, according to US research published in the online edition of AIDS. People taking antiretroviral therapy based on a protease inhibitor were especially likely to have a poor response to diabetes treatment.

Type-2 diabetes mellitus has emerged as an important cause of illness and death in people with HIV.

The exact reasons for this are unclear, but they seem to include traditional risk factors such as obesity, the side-effects of some anti-HIV drugs, the body composition changes caused by older antiretrovirals and the immune activation and inflammation caused by untreated HIV infection.

People with HIV also have an increased risk of cardiovascular disease. This makes the effective management of hyperglycaemia especially important in this group of individuals.

There is only limited information concerning responses to therapy for hyperglycaemia in people with HIV who also have diabetes. Investigators in Pennsylvania hypothesised that outcomes would be poorer in people with HIV compared to HIV-negative individuals. They therefore designed a retrospective study comparing reductions in haemoglobin A1c (HbA1c) between 286 people with HIV and 858 HIV-negative controls of the same sex and age during the first year of diabetes therapy.

Both the people with HIV and the people in the control group were starting therapy for type-2 diabetes for the first time. Almost all the people with HIV were taking antiretroviral therapy, the majority (53%) a regimen based on a protease inhibitor.

The people with HIV had lower baseline HbA1c values than the HIV-negative controls (7.82 vs 8.62%, p < 0.001).

Metformin was the most commonly used anti-diabetes drug (50% people with HIV vs 58% controls).

One year after treatment was started, the overall reduction in HbA1c was 1.04%.

The reductions in HbA1c recorded in people with HIV were significantly smaller than those seen in the HIV-negative controls (-0.17%, p = 0.003).

This difference could not be explained by the lower baseline HbA1c values seen in people with HIV.

Type of antiretroviral therapy was related to changes in HbA1c levels. People taking a protease inhibitor-based regimen, but not those on a non-protease inhibitor-containing regimen, achieved significantly smaller reductions in HbA1c compared to the controls (difference -0.21%, p = 0.002 in those on a protease inhibitor vs 0.10%, p = 0.21 in those not taking a protease inhibitor).

Changes in HbA1c did not differ according to CD4 cell count (above 200 cells/mm³ vs below 200 cells/mm³) nor by viral load.

According to American Diabetes Association guidelines the goal of diabetes therapy is HbA1c below 7% after one year. This outcome was achieved by 73% of the people with HIV compared to 59% of controls (p = 0.002).

However, “patients with type-2 diabetes and HIV infection who initiated diabetic medical therapy achieved smaller absolute reductions in HbA1c than patients with type-2 diabetes and no HIV infection in the course of routine clinical care,” write the authors. “The less robust response was more pronounced in HIV-infected patients on a protease inhibitor-based regimen…this finding is consistent with data indicating increased insulin resistance in recipients of protease inhibitors.”

The investigators also believe their overall findings of a poorer response in the people with HIV could “relate in part to persistent inflammation or immune activation, which has been associated with both HIV infection and insulin resistance”.

They believe that future studies should “evaluate optimal choice of pharmacologic therapy and the most accurate measurement of glycaemia” in people with HIV, “with the goal of decreasing the risk of clinical complications and mortality.”