Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4+ T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12–20 mo, viruses exhibited concentrated mutations at 17–34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses.
In order to effectively study the population experiencing insomnia, it is important to identify reliable and valid tools to measure sleep that can be administered in the home setting. The purpose of this study was to assess psychometric properties for the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in community-dwelling adults with primary insomnia. The CPSQI had an overall reliability coefficient of 0.82 -0.83 for all subjects. "Subjective sleep quality" was the component most highly correlated with the global score. Overall, the CPSQI showed acceptable test-retest reliability over a 14- to 21-day interval with a coefficient of 0.85 for all subjects and 0.77 for primary insomniacs. The two contrasting groups had significantly different global and component scores. A CPSQI of greater than 5 yielded a sensitivity and specificity of 98 and 55% in primary insomniacs vs. controls. A CPSQI of greater than 6 resulted in a sensitivity and specificity of 90 and 67%. Results suggest that the CPSQI is a psychometrically sound measure of sleep quality and disturbance for patients with primary insomnia. It may not be an effective screening tool because of its low specificity, but it can be a sensitive, reliable, and valid outcome assessment tool for use in community-based studies of primary insomnia.
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