Models using single-copy assay data revealed 3 phases of decay with RAL-containing ART, with a longer duration of first-phase decay consistent with RAL-mediated blockade of productive infection from preintegration complexes.
EFV and RIF-based tuberculosis therapy coadministration was associated with a trend toward higher, not lower, EFV Cmin compared to EFV alone. Patients weighing ≥60 kg had lower median EFV Cmin versus those <60 kg, but there was no association of higher weight with reduced virologic suppression. These data do not support weight-based dosing of EFV with RIF.
Purpose: We aimed to determine the association between vertebral strength by quantitative computed tomography (CT)-based finite element analysis (FEA) and incident vertebral fracture (VF). In addition, we examined sensitivity and specificity of previously proposed diagnostic thresholds for fragile bone strength and low BMD in predicting VF. Methods: In a case-control study, 26 incident VF cases (13 men, 13 women) and 62 age and sexmatched controls aged 50 to 85 years were selected from the Framingham multi-detector computed tomography cohort. Vertebral compressive strength, integral vBMD, trabecular vBMD, CT-based BMC, and CT-based aBMD were measured from CT scans of the lumbar spine.
BackgroundThe dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood. MethodsThirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy. ResultsInitiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy. ConclusionsART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis. Trial RegistrationClinicaltrials.gov NCT00660972
Background
We analyzed the early kinetics with integrase inhibitor treatment to gain new insights into viral dynamics.
Methodology
We analyzed data from 39 HIV-1 infected, treatment-naïve, participants; 28 treated with raltegravir (RAL; multiple doses) monotherapy for 9 days, and 11 with RAL 400 mg BID and emtricitabine (200 mg QD)/tenofovir disoproxil fumarate (300 mg QD). Plasma HIV-1 RNA was measured frequently; the data was fitted using a mathematical model of viral dynamics distinguishing between infected cells with unintegrated HIV DNA and productively infected cells. Parameters were estimated using mixed-effect models.
Results
RAL treatment led to a biphasic viral decline with a rapid first phase (1a) lasting ~5 days followed by a slower phase (1b). Phase 1a is attributed to the rapid elimination of productively infected cells. Phase 1b reflects the loss of infected cells with non-integrated provirus due to cell loss and integration of HIV DNA. The half-life of productively infected cells and of infected cells that had completed reverse transcription but had not yet integrated HIV DNA were ~19 h and between 3.6 and 5.8 days, respectively. The effectiveness of RAL in preventing HIV-1 integration was 94% and 99.7%, for the combination therapy and monotherapy groups, respectively.
Conclusion
We found that the first phase of viral decay with RAL therapy was composed of 2 subphases corresponding to the half-lives of infected cells with integrated proviruses and with unintegrated HIV-1 DNA.
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