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HIV persists in tissues during antiretroviral therapy (ART), but the relative contribution of different anatomical compartments to the viral reservoir in humans remains unknown. We performed an extensive characterization of HIV reservoirs in two men who donated their bodies to HIV cure research and who had been on suppressive ART for years. HIV DNA is detected in all tissues, with large variations across anatomical compartments and between participants. Intact HIV genomes represent 2% and 25% of all proviruses in the two participants and are mainly detected in secondary lymphoid organs, with the spleen and mediastinal lymph nodes harboring intact viral genomes in both individuals. Multiple copies of identical HIV genomes are found in all tissues, indicating that clonal expansions are common in anatomical sites. The majority (>85%) of these expanded clones are shared across multiple tissues. These findings suggest that infected cells expand, migrate, and possibly circulate between anatomical sites. [Display omitted] • In people on ART, half the HIV genomes in tissues are clonally expanded • Genetically intact HIV proviruses are more often found in lymphoid tissues • Identical proviral sequences are frequently found in distant tissues Dufour et al. study viral reservoirs by analyzing multiple samples from two men who donated their bodies for HIV cure research. They show that genetically intact proviruses are more often found in lymphoid organs. Moreover, half of the HIV genomes in tissues are clonally expanded and are frequently located in distant compartments. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one by Ernie Lightman, Dean Herd, and Andrew Mitchell on the analysis of the relationship of the labor force's welfare and the actual workfare state, one by Katherine Krull on the beneficial change in policy orientation from pro-natalism of pro-familism in Quebec, and one by Dennis Raphael on the association of health and distribution of income.

The article focuses on the significance of considering new public management (NPM) as paradigm. It talks about Thomas Kuhn's theory of paradigms, which includes law, theory, application and instrumentation, and its use for the social sciences. Three levels of paradigms in Kuhn's theory that were identified by two commentaries include metaphysical or epistemological, sociological, and exemplars or artefacts. The paradigms in social and applied sciences and their application to the new public management are discussed.

Tripartite-motif-containing protein 5 isoform α (TRIM5α) is a cytoplasmic antiretroviral effector upregulated by type I interferons (IFN-I). We previously showed that two points mutations, R332G/R335G, in the retroviral capsid-binding region confer human TRIM5α the capacity to target and strongly restrict HIV-1 upon overexpression of the mutated protein. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated homology-directed repair (HDR) to introduce these two mutations in the endogenous human TRIM5 gene. We found 6 out of 47 isolated cell clones containing at least one HDR-edited allele. One clone (clone 6) had both alleles containing R332G, but only one of the two alleles containing R335G. Upon challenge with an HIV-1 vector, clone 6 was significantly less permissive compared to unmodified cells, whereas the cell clones with monoallelic modifications were only slightly less permissive. Following interferon (IFN)-β treatment, inhibition of HIV-1 infection in clone 6 was significantly enhanced (~40-fold inhibition). TRIM5α knockdown confirmed that HIV-1 was inhibited by the edited TRIM5 gene products. Quantification of HIV-1 reverse transcription products showed that inhibition occurred through the expected mechanism. In conclusion, we demonstrate the feasibility of potently inhibiting a viral infection through the editing of innate effector genes. Our results also emphasize the importance of biallelic modification in order to reach significant levels of inhibition by TRIM5α. [ABSTRACT FROM AUTHOR]

Antivirals induce many significant side effects and reduce the quality of life for People Living with HIV (PLWHIV). The management of side effects is crucial to maintain the patient's quality of life and adherence to treatments. The patient-physician relation is essential when managing side effects as it influences the experience for the PLWHIV. This grounded theory analyzes the patient-physician relationship in context with side effects. In the greater Ottawa/Gatineau area, 50 PLWHIV have participated in a semi-structured interview to share their experience with side effects. Four categories were highlighted with this analysis : healthcare model, medical power (central category), strategies and impacts. Results show that physicians are in a monopoly position when taking charge of PLWHIV, who then develop mechanisms of selfpreservation against medical authority. Patients must also develop their own strategies to overcome side effects. Nevertheless, a conflictual relation between patient and physicians may cause multiple devastating effects for the PLWHIV (isolation, withdrawal and distress).