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Evaluating antibody maturation provides valuable data to characterize immune responses to HIV infection and can provide insight into biomedical intervention efficacy. It is important to develop assays that evaluate antibody maturation in both plasma and mucosal compartments. The nonhuman primate model provides a controlled system to collect temporal data that are integral to assessing intervention strategies. We report the development of a novel multiplex assay, based on the Bio-Plex platform, to evaluate plasma and mucosal IgG and IgA avidity and maturation against simian/human immunodeficiency virus (SHIV) in this controlled system. Vaginal mucosa and plasma samples were collected from a prior study evaluating the efficacy of a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR) against SHIVSF162P3 challenge in female pigtailed macaques. For validation of the multiplex assay, specimens from six SHIV-infected placebo animals and one TDF breakthrough animal were evaluated. For SHIV and HIV envelope analytes, antibody levels and avidity in both compartments continued to mature post-infection. Maturation of IgG and IgA levels was similar in each compartment, however, mucosal antibody levels tended to be more variable. This SHIV assay elucidates IgG/IgA antibody kinetics in the plasma and vaginal mucosa and will be a valuable tool in vaccine and other biomedical intervention studies in the nonhuman primate model. [ABSTRACT FROM AUTHOR]

HIV positive patients on highly active antiretroviral therapy (HAART) have shown elevated incidence of a number of non-AIDS defining co-morbidities, including cardiovascular disease. Given that HAART regimens contain a combination of at least three drugs, that disease management often requires adjustment of these regimens, and HIV, independent of HAART, also plays a role in development of co-morbidities, determining the role of specific HAART drugs and HIV infection itself from clinical data remains challenging. To characterize specific mediators and underlying mechanisms of disease, in vitro and in vivo animal models are required, in parallel with clinical data. Given its low cost azidothymidine (AZT) contributes to the backbone of a large proportion of HAART treated patients in the developing world where much of the global burden of HIV resides. The goal of this study was to test the hypothesis that AZT can lead to proatherogenic changes including the subclinical markers of arterial stiffening and intima-media thickening in mice. AZT (100 mg/kg) or vehicle was administered to wild-type FVB/N mice via oral gavage for 35 days. Cylindrical biaxial biomechanical tests on the common carotid arteries and suprarenal aortas exhibited arterial stiffening in AZT mice compared to controls. Multiphoton microscopy and histology demonstrated that AZT led to increased intima-media thickness. These data correlated with decreased elastin content and increased protease activity as measured by cathepsin zymography; no differences were observed in collagen content or organization, in vivo axial stretch, or opening angle. Thus, this study suggests the drug AZT has significant effects on the development of subclinical markers of atherosclerosis. [ABSTRACT FROM AUTHOR]