Low Bone Mineral Density, Renal Dysfunction, and Fracture Risk in HIV Infection: A Cross-Sectional Study

BackgroundReduced bone mineral density (BMD) is common in adults infected with human immunodeficiency virus (HIV). The role of proximal renal tubular dysfunction (PRTD) and alterations in bone metabolism in HIV-related low BMD are incompletely understood MethodsWe quantified BMD (dual-energy x-ray absorptiometry), blood and urinary markers of bone metabolism and renal function, and risk factors for low BMD (hip or spine T score, −1 or less) in an ambulatory care setting. We determined factors associated with low BMD and calculated 10-year fracture risks using the World Health Organization FRAX equation ResultsWe studied 153 adults (98% men; median age, 48 years; median body mass index, 24.5; 67 [44%] were receiving tenofovir, 81 [53%] were receiving a boosted protease inhibitor [PI]). Sixty-five participants (42%) had low BMD, and 11 (7%) had PRTD. PI therapy was associated with low BMD in multivariable analysis (odds ratio, 2.69; 95% confidence interval, 1.09-6.63). Tenofovir use was associated with increased osteoblast and osteoclast activity (P⩽.002). The mean estimated 10-year risks were 1.2% for hip fracture and 5.4% for any major osteoporotic fracture ConclusionsIn this mostly male population, low BMD was significantly associated with PI therapy. Tenofovir recipients showed evidence of increased bone turnover. Measurement of BMD and estimation of fracture risk may be warranted in treated HIV-infected adult

Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study

BACKGROUND: Reduced bone mineral density (BMD) is common in adults infected with human immunodeficiency virus (HIV). The role of proximal renal tubular dysfunction (PRTD) and alterations in bone metabolism in HIV-related low BMD are incompletely understood. METHODS: We quantified BMD (dual-energy x-ray absorptiometry), blood and urinary markers of bone metabolism and renal function, and risk factors for low BMD (hip or spine T score, -1 or less) in an ambulatory care setting. We determined factors associated with low BMD and calculated 10-year fracture risks using the World Health Organization FRAX equation. RESULTS: We studied 153 adults (98% men; median age, 48 years; median body mass index, 24.5; 67 [44%] were receiving tenofovir, 81 [53%] were receiving a boosted protease inhibitor [PI]). Sixty-five participants (42%) had low BMD, and 11 (7%) had PRTD. PI therapy was associated with low BMD in multivariable analysis (odds ratio, 2.69; 95% confidence interval, 1.09-6.63). Tenofovir use was associated with increased osteoblast and osteoclast activity (P< or = .002). The mean estimated 10-year risks were 1.2% for hip fracture and 5.4% for any major osteoporotic fracture. CONCLUSIONS: In this mostly male population, low BMD was significantly associated with PI therapy. Tenofovir recipients showed evidence of increased bone turnover. Measurement of BMD and estimation of fracture risk may be warranted in treated HIV-infected adults

Structure and Function Analysis of Therapeutic Monoclonal Antibodies against Dengue Virus Type 2▿ †

Dengue virus (DENV) is the most prevalent insect-transmitted viral disease in humans globally, and currently no specific therapy or vaccine is available. Protection against DENV and other related flaviviruses is associated with the development of antibodies against the viral envelope (E) protein. Although prior studies have characterized the neutralizing activity of monoclonal antibodies (MAbs) against DENV type 2 (DENV-2), none have compared simultaneously the inhibitory activity against a genetically diverse range of strains in vitro, the protective capacity in animals, and the localization of epitopes. Here, with the goal of identifying MAbs that can serve as postexposure therapy, we investigated in detail the functional activity of a large panel of new anti-DENV-2 mouse MAbs. Binding sites were mapped by yeast surface display and neutralization escape, cell culture inhibition assays were performed with homologous and heterologous strains, and prophylactic and therapeutic activity was evaluated with two mouse models. Protective MAbs localized to epitopes on the lateral ridge of domain I (DI), the dimer interface, lateral ridge, and fusion loop of DII, and the lateral ridge, C-C′ loop, and A strand of DIII. Several MAbs inefficiently inhibited at least one DENV-2 strain of a distinct genotype, suggesting that recognition of neutralizing epitopes varies with strain diversity. Moreover, antibody potency generally correlated with a narrowed genotype and serotype specificity. Five MAbs functioned efficiently as postexposure therapy when administered as a single dose, even 3 days after intracranial infection of BALB/c mice. Overall, these studies define the structural and functional complexity of antibodies against DENV-2 with protective potential

Magnetic Reconnection in Three Dimensions: Modeling and Analysis of Electromagnetic Drift Waves in the Adjacent Current Sheet

We present a model of electromagnetic drift waves in the current sheet adjacent to magnetic reconnection at the subsolar magnetopause. These drift waves are potentially important in governing 3‐D structure of subsolar magnetic reconnection and in generating turbulence. The drift waves propagate nearly parallel to the X line and are confined to a thin current sheet. The scale size normal to the current sheet is significantly less than the ion gyroradius and can be less than or on the order of the wavelength. The waves also have a limited extent along the magnetic field (B), making them a three‐dimensional eigenmode structure. In the current sheet, the background magnitudes of B and plasma density change significantly, calling for a treatment that incorporates an inhomogeneous plasma environment. Using detailed examination of Magnetospheric Multiscale observations, we find that the waves are best represented by series of electron vortices, superimposed on a primary electron drift, that propagate along the current sheet (parallel to the X line). The waves displace or corrugate the current sheet, which also potentially displaces the electron diffusion region. The model is based on fluid behavior of electrons, but ion motion must be treated kinetically. The strong electron drift along the X line is likely responsible for wave growth, similar to a lower hybrid drift instability. Contrary to a classical lower hybrid drift instability, however, the strong changes in the background B and no, the normal confinement to the current sheet, and the confinement along B are critical to the wave description