Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Nucleotide Sequences from Tryptophan Messenger RNA of Escherichia coli: The Sequence Corresponding to the Amino-Terminal Region of the First Polypeptide Specified by the Operon

Mutants with internal deletions that terminate near the operator end of the tryptophan operon of E. coli were used in studies on the nucleotide sequence at the 5' end of the messenger RNA transcribed on this operon. The findings obtained permitted identification of a sequence of 43 nucleotides corresponding to the aminoterminal 11 amino acids of anthranilate synthetase component I, the polypeptide specified by the operator-proximal structural gene of the operon. It was also shown that the translation initiation codon for this polypeptide is preceded on the messenger by a "leader" sequence of unknown function, at least 150 nucleotides in length.     

Purification and characterization of trp aporepressor.

We have isolated homogeneous trp aporepressor from an overproducing strain of Escherichia coli carrying a plasmid containing trpR preceded by tandem trp operon promoters. Dye-affinity and ion-exchange chromatography were used in conjunction with a gel electrophoresis assay in which the repressor, when bound to the trp operator, protects an Rsa I restriction site from endonuclease cleavage. Crystals suitable for x-ray diffraction studies were grown from a variety of concentrated salt solutions. Hydrodynamic properties and electrophoretic analysis of unmodified and covalently crosslinked aporepressor show that the free aporepressor has an isoelectric point of 5.9 and is a dimer containing two identical 12.5-kilodalton subunits in the presence or absence of L-tryptophan. The repressor . operator complex binds poorly to nitrocellulose filters, but restriction-site protection studies indicate that, in the presence of tryptophan, one dimer is bound to the operator site with an apparent dissociation constant less than 2 X 10(-9) M. Preliminary equilibrium dialysis experiments suggest that tryptophan binds to the aporepressor with a dissociation constant of 1.6 X 10(-5) M.     

Donor‐Derived Strongyloides stercoralis Infection in Solid Organ Transplant Recipients in the United States, 2009–2013

Infection with Strongyloides stercoralis is typically asymptomatic in immunocompetent hosts, despite chronic infection. In contrast, immunocompromised hosts such as solid organ transplant recipients are at risk for hyperinfection syndrome and/or disseminated disease, frequently resulting in fatal outcomes. Infection in these recipients may result from reactivation of latent infection or infection through transmission from an infected donor. We describe the Centers for Disease Control and Prevention's experience with seven clusters of donor‐derived infection from 2009 to 2013. Six of the seven (86%) donors were born in Latin America; donor screening was not performed prior to organ transplantation in any of these investigations. Eleven of the 20 (55%) organ recipients were symptomatic, two of whom died from complications of strongyloidiasis. We also describe the New York Organ Donor Network (NYODN) experience with targeted donor screening from 2010 to 2013. Of the 233 consented potential donors tested, 10 tested positive for Strongyloides antibody; and 18 organs were transplanted. The majority (86%) of the donors were born in Central or South America. Fourteen recipients received prophylaxis after transplantation; no recipients developed strongyloidiasis. The NYODN experience provides evidence that when targeted donor screening is performed prior to transplantation, donor‐derived infection can be averted in recipients.     

High affinity type I interleukin 1 receptor antagonists discovered by screening recombinant peptide libraries.

Two families of peptides that specifically bind the extracellular domain of the human type I interleukin I (IL-1) receptor were identified from recombinant peptide display libraries. Peptides from one of these families blocked binding of IL-lalpha to the type I IL-1 receptor with IC50 values of 45-140 microM. Affinity-selective screening of variants of these peptides produced ligands of much higher affinity (IC50 approximately 2 nM). These peptides block IL-1-driven responses in human and monkey cells; they do not bind the human type II IL-1 receptor or the murine type I IL-1 receptor. This is the first example (that we know of) of a high affinity peptide that binds to a cytokine receptor and acts as a cytokine antagonist.