Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status

Abstract

Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency virus (HIV)-associated neurological injury; however, this relationship has not been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52 HIV and 21 seronegative participants of the Chicago Early HIV Infection study. MMP levels were also examined in HIV subgroups defined by antibody reactivity, viremia, and antiretroviral status, as well as in available cerebrospinal fluid (CSF) samples (n = 9). MMPs were evaluated for patterns of relationship to cognitive function and to quantitative magnetic resonance measurements of the brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early HIV infection and correlated with altered white matter integrity and atrophic brain changes. MMP-9 levels were higher in the treated subgroup than in the naïve HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated with white matter integrity and with volumetric changes in basal ganglia. Relationships with cognitive function were also identified. MMP-2 levels in plasma and in CSF correspond to early changes in brain structure and function. These findings establish a link between MMPs and neurological status previously unidentified in early HIV infection.

Fig. 1

Boxes represent interquartile range (IQR). Whiskers represent data points within 1.5 IQRs of the box. A significant downward linear trend was seen for plasma MMP-2 with respect to HIV progression as grouped by antibody reactivity (p < 0.001; deviation p = 0.921). Mean MMP-2 level was reduced in the HIV antibody reactive group compared to the nonreactive group (p = 0.030). When compared to the control group, MMP-2 levels differed significantly for the antibody-reactive HIV subgroup (p < 0.001) and approached significance for the very early, nonreactive HIV subgroup (p = 0.091)