Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4 ؉ T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naïve animal induced memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In parallel, genomic DNA from the blood donor was amplified to generate the late proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV1157ipd3, an extra NF-B binding site was engineered into its 3 long terminal repeat, giving rise to SHIV1157ipd3N4. This virus was exclusively R5 tropic and replicated more potently in rhesus peripheral blood mononuclear cells than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus macaques of Indian and Chinese origin were next inoculated intrarectally with SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally transmissible R5 SHIV that represents a valuable tool to test candidate AIDS vaccines targeting HIV-1 clade C Env.
Human immunodeficiency virus clade C (HIV-C) accounts for >56% of all HIV infections worldwide. To investigate vaccine safety and efficacy in nonhuman primates, a pathogenic, R5-tropic, neutralization-sensitive simian-human immunodeficiency virus (SHIV) carrying HIV-C env would be desirable. We have constructed SHIV-2873Ni, an R5-tropic SHIV carrying a primary pediatric HIV-C env gene isolated from a 2-month-old Zambian infant, who died within 1 year of birth. SHIV-2873Ni was constructed using SHIV-1157ipd3N4 (R.
Overcrowding and prolonged patient length-of-stay (LOS) in emergency departments (EDs) are growing problems. We evaluated the impact of implementing a rapid whole blood quantitative D-dimer test (Biosite Triage, Biosite Diagnostics, San Diego, CA) in our ED satellite laboratory on 252 patients before vs 211 patients after implementation. All patients also underwent testing with the existing central laboratory method (VIDAS D-dimer, bioMérieux, Durham, NC). D-dimer turnaround time (from blood draw to result) decreased approximately 79% (approximately 2 hours vs 25 minutes). The mean ED LOS declined from 8.46 to 7.14 hours (P = .016). Hospital admissions decreased 13.8%, ED discharges increased 7.3%, and the number of patients admitted for observation increased 6.4% (P = .005). No difference in the utilization of radiologic studies was observed (P = .86). At 3 months' follow-up, none of the after-implementation patients with negative D-dimer results were admitted for subsequent venous thromboembolic disease. The rapid D-dimer test was associated with a shorter ED LOS and fewer hospital admissions.
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