Children infected with HIV show early signs of cardiovascular disease, particularly if they have been treated with protease inhibitors, according to the results of a study presented in the 5th July edition of Circulation. This suggests that children with HIV may be at an elevated risk of heart attack or stroke during adolescence or early adulthood.
HIV infection and treatment with anti-HIV drugs are known to be risk factors for the development of cardiovascular disease in adults, resulting in an increased incidence of premature cardiovascular events like heart attacks or strokes. However, fewer data are available on the risk of cardiovascular disease faced by HIV-positive children.
To assess this risk, investigators from Great Ormond Street Hospital in London studied 83 children aged between five and 18 years who had been infected with HIV via mother-to-child transmission. The researchers measured the structure and function of their blood vessels, comparing them to measurements from a group of 59 HIV-negative children.
“Structural and functional changes of the vasculature are already present during childhood in HIV-infected children,” they write. “These changes were most pronounced in children receiving protease inhibitors but were also observed in non-protease inhibitor-treated and untreated children.
“Our findings support a role for both HIV infection itself and antiretroviral therapy, particularly protease inhibitors, in the pathogenesis of early vascular disease,” they conclude.
The HIV-positive children had greater carotid intima-media thickness (IMT) than the HIV-negative controls (mean 0.6 vs. 0.47mm; p
The investigators also found that both age and HIV treatment were associated with IMT in the HIV-positive children. Since all of the children were infected through mother-to-child transmission, age is an approximate marker of the duration of infection in this group, suggesting that both HIV infection and treatment are linked to blood vessel damage.
The 31 children who had received protease inhibitors had a greater IMT than the 25 who had received anti-HIV treatment that did not contain protease inhibitors (p = 0.04) and the 27 who had received no treatment (p = 0.01). However, IMT was not linked to CD4 cell percentage or viral load.
The investigators also measured the flexibility of the children’s blood vessels using flow-mediated dilatation (FMD) with ultrasound scans of an artery in the arm. They found that FMD was significantly reduced in the HIV-positive children (7.9 vs. 9.4%; p = 0.02), and that the children who had been treated with protease inhibitors showed lower FMD scores than those who had received protease inhibitor-sparing treatment (p = 0.05) and those who had never been treated (p
The HIV-positive children also had raised levels of triglycerides, non-high density lipoprotein (HDL) cholesterol, apolipoprotein B and lipoprotein (a). The children who had taken anti-HIV therapy, particularly those with experience of protease inhibitor-based treatment, had higher levels.
“Because death rates among HIV-infected children have decreased fivefold since the introduction of the highly active antiretroviral treatment, careful long-term monitoring appears warranted to detect emerging cardiovascular disease,” the researchers conclude.
However, they admit that their results require confirmation in studies that follow children over time, in order to understand the separate contributions of HIV and its treatment more fully.
“Longitudinal studies are required to differentiate the relative impact of HIV disease and antiretroviral therapy and to assess the potential for prevention,” they write.
Charakida M et al. Early structural and functional changes of the vasculature in HIV-infected children. Impact of disease and antiretroviral therapy. Circulation 112: 103-109, 2005.