Decrease in LDL size in HIV-positive adults before and after lopinavir/ritonavir-containing regimen: an index of atherogenicity?

BACKGROUND: Hypertriglyceridemia (HTG) is frequently observed during highly active antiretroviral therapy (HAART) including protease inhibitor. Apolipoprotein (apo) CIII could be involved in this HTG by inhibition of triglyceride (TG) hydrolysis, which leads to the occurrence of small dense low density lipoprotein (sdLDL), a recognized cardiovascular risk factor. OBJECTIVE: To characterize the influence of lopinavir/ritonavir-containing regimen on lipoprotein profile. DESIGN AND METHODS: 24 antiretroviral-experienced HIV infected adults (including 14 patients in therapeutic interruption of at least 2 months) and 14 HIV uninfected healthy controls were enrolled. Serum lipid parameters (total cholesterol (TC), HDL-C, LDL-C, TG, apoA1, apoB, apoCIII), lipoprotein composition and LDL size were determined before initiation of lopinavir/ritonavir-containing regimen, and at 1 and 3 months thereafter. RESULTS: At baseline an atherogenic lipid profile was evidenced, characterized by a moderate HTG associated to a smaller mean LDL size (25.16 vs 25.93 nm, P<0.001), an enrichment in TG of LDL (11.4 vs 6.0%, P<0.01) and a high prevalence of sdLDL (75 vs 7%, P<0.01) when compared to controls. After 1 month of lopinavir/ritonavir-containing regimen, a significant reduction of LDL size (24.81 vs 25.16 nm, P<0.05) and a significant increase in cholesterol total (5.53 vs 4.49 mmol/l, P<0.001), in TG (4.20 vs 2.01 mmol/l, P<0.001), in apoA1 (1.28 vs 1.11 g/l, P<0.001), in apoB (1.08 vs 0.94 g/l, P<0.01), in apoCIII (0.16 vs 0.10 g/l, P<0.001), in TG percentage in LDL (14.4 vs 11.4, P<0.05) and in TG percentage in HDL (10.2 vs 8.3, P<0.05) were observed. CONCLUSIONS: Advanced stage of HIV infection is associated with an atherogenic lipid profile including a high prevalence of sdLDL. Lopinavir/ritonavir-containing regimen accentuates the reduction of LDL size. Since fibrates decrease TG and increase LDL size, they appear as a logical option to manage HAART-induced HTG.

CD4 T cell surface CCR5 density as a host factor in HIV-1 disease progression.

OBJECTIVE AND DESIGN: We have recently shown that the number of CCR5 molecules at the surface of peripheral blood CD4 T cells (CCR5 density) correlates with the viral RNA plasma level in HIV-1-infected individuals. As viral load is a strong predictor of outcome in HIV infection, the present study examines the correlation between CCR5 density and HIV-1 disease progression. METHODS: Using a quantitative flow cytometry assay, we measured CCR5 density in HIV-1-infected adults and control healthy volunteers. The CCR5 genotype (presence of a Delta 32 allele) was also determined. RESULTS: CCR5 density was stable over time on non-activated, HLA-DR(-)CD4 T cells of infected individuals. In a study cohort of 25 patients, asymptomatic and non-treated, we observed a correlation between CCR5 density on HLA-DR(-)CD4 T cells and the CD4 T cell slope (P = 0.026), which was independent of the presence or absence of the Delta 32CCR5 deletion. In particular, slow progressors expressed lower CCR5 densities than non-slow progressors (P = 0.004) and non-infected control subjects (P = 0.002). CONCLUSION: These results are compatible with the hypothesis that CCR5 density, which is a key factor of HIV-1 infectability, determines in-vivo HIV production, and thereby the rate of CD4 cell decline. Consequently, CCR5 density quantitation could be a new valuable prognostic tool in HIV-1 infection. Moreover, these data emphasize the therapeutic potential of treatments that reduce functional CCR5 density.

In vitro anti-Toxoplasma gondii antibody production by peripheral blood mononuclear cells in the diagnosis and the monitoring of toxoplasmic encephalitis in AIDS-related brain lesions.

The spontaneous secretion in vitro of anti-Toxoplasma gondii antibodies by peripheral blood mononuclear cells was assessed in 69 patients with AIDS-related brain lesions. The sensitivity and specificity of this assay in the diagnosis of toxoplasmic encephalitis (TE) were found to be 85.4% and 92.8%, respectively. Twenty-four patients with TE were observed during 1-year follow-up after initiation of anti-Toxoplasma treatment and classified on the basis of their clinical and radiologic responses as sustained responders (SR; n = 11), incomplete responders (IR; n = 7) or transient responders (TR; n = 6). In vitro anti-T. gondii antibody secretion decreased as early as the first month after initiation of treatment and disappeared within the year in SRs, persisted in IRs, and decreased but rebounded at relapse in the TR patients. In vitro anti-T. gondii antibody, which reflects immune system activation by parasitic antigens, could be a surrogate marker of TE in AIDS patients.

CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1.

The intensity of expression of the chemokine receptor CCR5 is involved in in vitro cell infectability by human immunodeficiency virus (HIV)-1 R5 isolates. Because CCR5 expression varies among individuals, the hypothesis that this expression could determine virus load in HIV-1-infected persons was tested. The mean number of CCR5 molecules per cell was measured on peripheral blood CD4+ T lymphocytes (CCR5 density) from HIV-1-infected, asymptomatic, nontreated adults. There was a strong correlation between HIV RNA plasma level and CCR5 density (P=.009) that was independent of cell activation and was not due to an HIV-induced CCR5 up-regulation. These data are compatible with the hypothesis that CCR5 density is a key factor governing cell infectability and in vivo virus production and explain the protective effect of the Delta32CCR5 deletion, which results in low CCR5 expression. CCR5 density might be of critical predictive value in HIV infection.