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CROI: Insulin resistance common in HIV-positive children
Chris Gadd & Liz Highleyman, Tuesday, February 07, 2006
HIV-positive children have higher rates of resistance to the hormone insulin than children without HIV, according to the results of a study presented this morning at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver. This puts them at an elevated risk of developing diabetes and cardiovascular disease later in life.

Metabolic changes in HIV-positive patients have been linked both to HIV itself and to HIV treatment, notably with protease inhibitors. Although many studies have concentrated on adults, experts are concerned that children infected with HIV may also be at risk of these changes, one component of which is a decrease in the body’s responsiveness to insulin, the hormone that helps regulate blood sugar levels.

To assess this risk, investigators from the University of Genoa in Italy measured the degree of insulin resistance in a cohort of 47 HIV-positive children, adolescents and young adults aged three to 23 years.

Compared to a control group of 148 HIV-negative patients of similar ages, the HIV-positive group had higher levels of insulin resistance, as detected in three measures: the homeostasis model assessment (HOMA-IR), the HOMA of percentage of β-cell function (HOMA-β%) and the quantitative insulin-sensitivity check index (QUICKI).

The children with HIV had a higher mean HOMA-IR score (2.58 vs. 1.49; p < 0.001), higher mean HOMA-β% (357 vs. 145; p < 0.001), and a lower mean QUICKI score (0.35 vs. 0.37; p < 0.001).

The HIV-positive children also had higher mean blood insulin levels than those without HIV (13.5 vs. 7.1 mU/l; p < 0.001), and lower glucose levels (4.32 vs. 4.68mmol/l; p < 0.001). Twenty-six (54%) of the HIV-infected children had an insulin to glucose ratio below 7, which is commonly considered the cut-off for insulin resistance. Only 21 (14%) of the HIV-negative patients had these levels of insulin resistance.

Among the children with HIV, 36 (75%) were receiving HIV treatment regimens containing a protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI), nine (19%) were receiving only two nucleoside reverse transcriptase inhibitors (NRTIs), and three (6%) had never taken any antiretroviral therapy. However, the investigators did not attempt to examine the effect of different types of HIV treatment or time taking HIV treatment because of the small sample size.

“Insulin resistance … could be related [not only to] cumulative antiretroviral therapy exposure but the HIV infection itself,” the investigators explained. “The association between type and duration of highly active antiretroviral therapy and insulin resistance was not considered, due to the small group size and the widely different types of therapy received by [the] patients.”

In conclusion, Raffaella Rosso, presenting, recommended that blood fat and glucose levels be monitored in HIV-positive children to help detect metabolic abnormalities early. She also suggested a range of treatments for insulin resistance in HIV-positive children, including exercise, healthy diets, and, possibly, avoidance of anti-HIV drugs linked to the syndrome, such as protease inhibitors and d4T (stavudine, Zerit).

Following Dr Rosso’s presentation, Grace McComsey from Rainbow Babies’ and Children’s Hospital in Cleveland gave a comprehensive overview of research into metabolic abnormalities in HIV-positive children. She highlighted the difficulties in carrying out these studies, including the small number of children available for recruitment, difficulties in accounting for normal fluctuations in hormones, and practical issues surrounding trials involving children.

Echoing Dr Rosso’s conclusions, she emphasised the serious complications that are associated with HIV treatment in children, including body fat changes, raised blood fat and sugar levels, lactate elevations, reductions in bone density and insulin resistance.

Her summary demonstrated the confusion caused by conflicting findings from studies into metabolic changes in HIV-positive children, emphasising the need for more studies to help paediatricians and HIV doctors understand the risks associated with HIV treatment in younger patients.

References

Rosso R et al. Insulin resistance, lipodystrophy and associated metabolic changes in HIV-infected children. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 23, 2006.

McComsey G et al. The price of antiretroviral therapy in children: focus on metabolic morbidities. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 24, 2006.