We hypothesized that the links between spirituality and lower HIV-related stigma would be accounted for by lower levels of shame, and that this mediation model would be moderated by ethnicity in 106 people living with HIV (PLWH). Moderated mediation analyses revealed that higher spirituality was associated with reduced levels of shame, which in turn was associated with lower levels of HIV-related stigma. The indirect effect of spirituality on lower stigma through reduced shame was significant for White but not for Non-White PLWH. It is possible that other mechanisms exist to explain how spirituality operates on stigma for minorities living with HIV.

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Vpr is a 14 kDa accessory protein conserved amongst extant primate lentiviruses that is required for virus replication in vivo. Although many functions have been attributed to Vpr, its primary role, and the function under selective pressure in vivo, remains elusive. The minimal importance of Vpr in infection of activated CD4+ T cells in vitro suggests that its major importance lies in overcoming restriction to virus replication in quiescent CD4+ T cells and non-cycling myeloid cell populations, such as macrophages and dendritic cells. Previous studies from our laboratory demonstrated that HIV-1 replication is attenuated in the absence of Vpr in monocyte-derived dendritic cells (MDDCs) and macrophages, which is correlated with the ability of HIV-1 Vpr to overcome a post-integration transcriptional defect in these cells. In contrast to HIV-1 Vpr-mediated transcriptional enhancement of the viral LTR, here I describe a role for HIV-2 and SIVmac Vpr homologs in the suppression of innate immune sensing of primate lentiviral infection in monocyte-derived dendritic cells (MDDCs). Specifically, the Vpr proteins of HIV-2 and SIVmac, but not that of HIV-1, suppress innate immune detection and induction of type I and type III IFN at two distinct stages of the viral life cycle: prior to and during integration. We posit that HIV-2/SIVmac-lineage Vpr homologs gained this function upon the acquisition of Vpx, a Vpr paralog in the lentiviral genome, that targets the retroviral restriction factor SAMHD1 for proteasomal degradation. Mutational analysis shows that suppression of pre-integration innate immune sensing by HIV-2/SIVmac Vpr homologs is tied to their interaction with the DNA damage response protein human Uracil DNA glycosylase hUNG. Interestingly, the HIV-1 Vpr degrades hUNG, whilst the HIV-2/SIVmac Vpr homologs do not. This difference correlates with the inability of HIV-1 Vpr to suppress type I and III IFN responses in SIVmac Vpx supplemented infections of MDDCs. These results highlight how divergent lentiviruses have tailored interactions of their Vpr proteins with members of the DNA damage response to promote replication in diverse cellular contexts. This work also describes the conserved role of primate lentiviral Vpr homologs in the transcription of extrachromosomal or unintegrated viral DNA. This function is dependent on Vpr engagement with the host E3-ubiquitin ligase complex Cul4-DDB1-DCAF1 (DCAFCRL4) and ability to activate the DNA damage response. These findings give insight into the mechanisms driving transcription from an underappreciated and long-lived source of viral antigen, and further the field of non-integrating lentiviral vectors, a frequently used tool for the genetic modification of non-dividing cells. Together, both studies shed light on the way Vpr proteins from diverse primate lentiviruses converge in their manipulation of the DNA damage response to facilitate multiple stages of the virus lifecycle. / 2024-01-24T00:00:00Z

In this study, a Monte Carlo simulation was designed to observe the self-assembly of the HIV-1 capsid protein. The simulation allowed a coarse grained model of the capsid protein with defined interaction sites to move freely in three dimensions using the Metropolis criterion. Observations were made as to which parameters affected the assembly the process. The ways in which the assembly were affected were also noted. It was found that proper dimerization of the capsid protein was necessary in order for the lattice to form properly. It was also found that a strong trimeric interface could be responsible for double-layered assemblies. Further studies may be conducted by further varying of parameters or reworking the dynamics of the simulation. The possible causes of curvature within the assembly still need to be researched further.

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Infant Feeding in HIV in Canada is an increasingly challenging and confusing aspect of clinical care for providers and patients due to differences in recommendations in Canada compared to low income countries. The frequency of breastfeeding occurring in Canada is not documented or known, and is shrouded in stigma because of fear of criminalization or child apprehension in the midst of a culture where ‘breast is best’ messaging dominates. Breastmilk transmission data comes from observational and randomized controlled trials completed in low resource settings, which may not be generalizable to Canadian clinical settings. Previous literature has not explored provider perspectives on this issue, especially in high resource settings. We developed a survey to explore the knowledge, attitudes and practices of adult and pediatric HIV care providers in Canada. This survey explores the provider knowledge levels, risk tolerance and perceived stigma pertaining to infant feeding in HIV. Using exploratory analysis including descriptive statistics and regression modelling, we developed scales on the above listed three subject areas. The overall opinions of providers were that formula feeding should remain the recommendation due to the potential risk to the infant; and that women should be supported to access formula and resources to overcome barriers to formula feeding. Providers varied in their risk tolerance and the degree of stigma they perceived associated with infant feeding for their patients. Providers did not feel that breastfeeding is a criminal matter, but in some circumstances they would consider involving child protection services. Focus group consultation with women living with HIV, provided insight into the experiences, and clinical and research priorities for women living with HIV on infant feeding. A provider meeting was organized to discuss the challenges and resources pertaining to infant feeding in Canada across the provinces. Providers described diverse patient populations with differing needs. Using a World Café model for discussion, priority needs were decided through consensus including the need for knowledge translational resources to convey information to women living with HIV on infant feeding, and the need for evidence based consensus clinical management guidelines was evident. Quantifying the frequency of breastfeeding occurring in Canada by women living with HIV will help to understand how often this issue is encountered. A preliminary qualitative approach to understanding infant feeding issues for women living with HIV using focus groups is described. However, further exploration in a community based approached is needed to explore the needs and challenges faced by families affected by HIV around infant feeding. / Thesis / Master of Science (MSc) / Infant Feeding in HIV in Canada is an increasingly challenging aspect of clinical care. Information on breastmilk transmission comes from studies completed in lower income countries, and this may not be applicable to the Canadian HIV setting. Previous literature has not explored provider perspectives on this issue, especially in high-income countries like Canada. In this knowledge, attitudes and practices survey of HIV care providers in Canada, the main findings were that formula feeding should remain the recommendation due to the potential risk of HIV infection occurring in the baby, however women should be supported to access formula and resources to overcome barriers to formula feeding. Providers do not feel that breastfeeding is a criminal matter, but in some circumstances may consider involving child protection services. We performed community consultation using focus groups to understand some of the issues women face with infant feeding, some of the clinical solutions they would support, and research questions and knowledge translation they would want undertaken. A provider meeting to discuss the challenges pertaining to infant feeding in Canada demonstrated that although populations differ, the need for knowledge translational resources to convey information to women living with HIV on infant feeding was universal. Furthermore, the need for evidence based consensus clinical management guidelines would improve the quality of care provided.