The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.).

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Heat shock or stress proteins (Hsp) are typically regarded as being intracellular proteins that have a range of functions including the maintenance of cellular integrity. Members of the Hsp70 family of molecules have been implicated in the processing and presentation of antigen and the cross reactivity of lymphocytes specific for pathogen-derived heat shock proteins with self Hsp70 has been suggested to be an underlying cause of certain autoimmune diseases. This study reports the presence of soluble Hsp70 in the peripheral circulation of normal individuals. Concentrations of soluble Hsp70 in females were approximately twice those in males. Circulating anti-Hsp70 antibodies were detected in all individuals assessed, but there were no differences between males and females. However, there was a significant correlation between soluble Hsp70 concentration and antibody levels in males, but not females. The physiological role for circulating heat shock proteins is intriguing, but currently unknown. These findings extend our previous observations that Hsp60 is present in the peripheral circulation and support the proposition that soluble heat shock proteins may play a regulatory role in either the prevention or protection of pathophysiological processes involving inadvertent immunorecognition or cross-recognition of heat shock proteins.

Background Newly infected subjects acquire a limited number of human immunodeficiency virus type 1 (HIV-1) variants with specific genotypic and phenotypic features from the array of viruses present in a chronically infected transmitting partner. Methods We examined HIV-1 envelope sequences from the earliest available serum sample after HIV-1 acquisition in 13 newly infected subjects and from their epidemiologically linked HIV-1–infected heterosexual partner. Samples from both members were collected on the same day in the Rakai Community Cohort Study. Results Ten couples were infected with subtype D HIV-1, and 3 pairs had subtype A HIV-1. Newly infected subjects acquired a subset of the viruses that were circulating in the transmitting partner; transmitted variants had less diversity and divergence and were more closely related to the ancestral sequences. The majority of signature amino acid differences among donor and recipient sequences were in and immediately following the V3 loop. Envelopes from recipients were significantly shorter and had a lower V3 charge than envelopes from donors, but there was no significant difference in the number of potential N-linked glycosylation sites. Conclusion A minority subset of HIV-1 variants with signature genotypes is favored for transmission in this population.

SummaryThe transporter associated with antigen processing (TAP) delivers peptides to the lumen of the endoplasmic reticuhm in an adenosine triphosphate (ATP) dependent fashion for presentation by major histocompatibility complex class I molecules. We show that the mouse TAP translocator (H-2 b haplotype) sdects peptides based on a minimal size of nine residues, and on the presence of a hydrophobic COOH-terminal amino add. The preponderance of COOH-terminal hydrophobic amino acids in peptides capable of binding to mouse class I molecules thus fits remarkably well with the specificity of the TAP translocator. In addition to transport in the lumenal direction, eit]ux of peptide in the cytosolic direction is observed in an ATP-and temperature-dependent manner. By maintaining a low peptide concentration at the site of class I assembly, this efl:hx mechanism may ensure that class I molecules are loaded preferentially with high affinity peptides.

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We examined the emergence of CXCR4 (i.e., X4) tropism in 67 male human immunodeficiency virus type 1 (HIV-1) seroconverters from the Multicenter AIDS Cohort Study (MACS) who were selected to reflect the full spectrum of rates of HIV-1 disease progression. A mean of 10 serial samples per donor were evaluated by a laboratory-validated, commercially available assay to determine phenotypic coreceptor use. A total of 52% of men had dual- or mixed-tropic HIV-1 detected at 1 or more of the time points tested. Use of X4 by HIV-1 was detected more frequently among men who developed AIDS (defined as a CD4+ T cell count of < 200 cells/μL and/or an AIDS-defining illness)≤11 years after seroconversion than among those who did not (P = .005), as well as among men who exhibited a total T cell count decline (i.e., a CD3+ inflection point), compared with those who did not (P = .03). For men in whom both X4 virus and an inflection point were detected, emergence of X4 virus preceded the inflection point by a median of 0.83 years. The median CD4+ T cell count at first detection of X4 viruses before the onset of AIDS was 475 cells/μL. We conclude that HIV-1 variants that used X4 frequently emerged at high CD4+ T cell counts and may contribute to the decrease in T cell numbers during late HIV-1 infection.