Understanding How Displacement Affects Hiv Prevalence Among Displaced Populations- A Scoping Review

Over the course of the past two decades, the number of people who have been displaced has increased dramatically. With this brings a new set of health challenges for these populations as well as the countries to which these populations are displaced such as HIV/AIDS. There is evidence to show that forced displacement can cause an increase in the HIV prevalence among those displaced. However, there is evidence to suggest the contrary, as well. The aim of this scoping review study is to determine what the existing literature can and cannot tell us about how forced displacement affects HIV prevalence among those displaced. With this better understanding of existing literature, further research can be planned more effectively to fill in existing gaps. A scoping review protocol was developed and two databases, PubMed and Medline, were scanned for articles that met the inclusion criteria. In total, 636 article titles and abstracts were scanned and of these, 85 articles were read in full and 25 were deemed to meet the inclusion criteria. Analysis of the extracted data revealed a potential influence of the HIV prevalence of the country being fled to and the HIV prevalence of the displaced group. If the HIV prevalence of a country or region was high, the HIV prevalence of displaced groups fleeing to these regions were higher. The same trend was seen with HIV low regions and a lower HIV prevalence in displaced groups. The scoping review also showed a lack of proper studies having been done to answer this particular question. There was also a lack of studies of certain regions of the world regarding HIV prevalence among displaced populations such as the Middle East and Central and Southern America. In order to answer this question more effectively, a longitudinal study of a fixed population should be done to determine how forced displacement affects HIV prevalence among those displaced

Public Health Implications of Evictions: Modeling the Costs for Landlords, Tenants, and Society

In the United States, more than 13% of renters experience a formal or informal eviction in their lifetime. Forced moves contribute to a decline in job status, mental and physical health, material possessions, safety, social networks, housing aid, and neighborhood stability. Previous research has explored the risk factors, causes, and costs to those burdened by evictions. However, the costs of evictions incurred by all stakeholders involved in the process of evictions and homelessness remain largely unexplored. The homeownership rate in New Haven is less than 30%, and more than 52% of households are ‘cost-burdened,’ meaning more than 30% of income “is spent on housing costs associated with owning or renting a home.” Thus, this project set out to analyze the contributing burdens of costs within New Haven, Connecticut.https://elischolar.library.yale.edu/ysph_pbchrr/1016/thumbnail.jp

Higher HIV-1 Env gp120-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity Is Associated with Lower Levels of Defective HIV-1 Provirus

Thesis (Ph.D.)--University of Washington, 2023During HIV-1 (HIV) infection, continued administration of antiretroviral therapy (ART) can decrease a person’s viral load to undetectable levels and allow for a near-normal lifespan, though ART is not a cure due to a reservoir of cells that harbor latent, integrated HIV provirus capable of host immune evasion and stochastic reactivation. While the vast majority of HIV proviruses are defective due to large internal deletions or hypermutations, a fraction of proviruses are intact and replication competent which contribute to the rebound of viremia that occurs upon cessation of ART, necessitating its life-long administration. The majority of archived proviral sequences that persist on ART are genetically similar to those of circulating viruses at the time of ART initiation which suggests that factors present at this time can impact HIV reservoir dynamics, and that additional influences at this critical time for reservoir establishment may also be identified. Host immune responses such as Antibody-Dependent Cellular Cytotoxicity (ADCC), which act to clear infected cells, have been suggested to have the potential to impact reservoir size and characteristics. Children living with HIV represent a significant fraction of people living with HIV, yet studies of the pediatric HIV reservoir, especially those focused on its establishment during chronic HIV infection, are relatively few compared to those in adults. The work detailed in this thesis tested the hypothesis that the ability of autologous plasma antibodies to mediate ADCC against HIV Env at the time of ART initiation inversely correlates with the size of the established HIV reservoir. This was done using samples from the Pediatric Adherence Diary study, the rapid and fluorometric ADCC (RFADCC) assay, and the Cross-Subtype Intact Proviral DNA assay (CS-IPDA). The results demonstrated a moderate, inverse correlation between HIV Env gp120-specific ADCC activity in plasma at the time of ART initiation and the level of defective (r = -0.285, p-value = 0.0214), but not intact (r = -0.0321, p-value = 0.800), HIV proviral copies that persist during ART. These findings suggest that host immune factors prior to ART initiation may impact the proviruses that persist during ART. Additionally, it adds to the mounting evidence that cells harboring defective HIV provirus may face different immune selection pressures than cells harboring intact provirus

CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo.

Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people. Further, genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. RNA profiling confirmed expression of HIV receptor RNA in a pattern that was consistent with in vitro and in vivo results. In addition, we characterized a CD4high HSPC sub-population that was preferentially targeted by a variety of CXCR4- and CCR5-tropic HIVs in vitro. Finally, we present strong evidence that HIV proviral genomes of both tropisms can be transmitted to CD4-negative daughter cells of multiple lineages in vivo. In some cases, the transmitted proviral genomes contained signature deletions that inactivated the virus, eliminating the possibility that coincidental infection explains the results. These data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for CXCR4- and CCR5-tropic HIV proviral genomes that can be passed to daughter cells

CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo

<div><p>Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people. Further, genotypic and phenotypic analysis of amplified <i>env</i> alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. RNA profiling confirmed expression of HIV receptor RNA in a pattern that was consistent with in vitro and in vivo results. In addition, we characterized a CD4^high HSPC sub-population that was preferentially targeted by a variety of CXCR4- and CCR5-tropic HIVs in vitro. Finally, we present strong evidence that HIV proviral genomes of both tropisms can be transmitted to CD4-negative daughter cells of multiple lineages in vivo. In some cases, the transmitted proviral genomes contained signature deletions that inactivated the virus, eliminating the possibility that coincidental infection explains the results. These data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for CXCR4- and CCR5-tropic HIV proviral genomes that can be passed to daughter cells.</p></div

Summary of donor <i>env</i> amplicons in Sort 1 and 2 HSPCs.

<p>Summary of donor <i>env</i> amplicons in Sort 1 and 2 HSPCs.</p

Summary of Env phenotypes with V3 regions matching HSPC-associated <i>env</i> sequences.

<p>Summary of Env phenotypes with V3 regions matching HSPC-associated <i>env</i> sequences.</p

Targeting of intermediate progenitors by CCR5-tropic Envs is a conserved property extending to a transmitted/founder virus.

<p>A. Schematic of HIV-7/SF-GFP construct and HIV envelope plasmid used to construct pseudotyped viruses used in C-E. B. Summary table of envelope proteins used to pseudotype HIV-7/SF-GFP virus. C. Representative flow plots of cord blood-derived CD133-sorted cells expanded for four days, transduced with the indicated virus and harvested 3 days post-infection for flow cytometric analysis. In each right panel, GFP⁺ cells were overlaid onto plots of the total cell population and the percentage of GFP⁺ cells in the CD133^high and CD133^low regions is indicated. Gates were determined based on isotype control antibody staining (top panel). D. Summary graph of CD133 MFI for experiments performed as in C. Results are compiled from 11 cord blood experiments. Mean ± standard deviation is indicated; <i>n</i>≥3 for each envelope. 2-tailed Student’s t-test indicates significance for each HIV envelope with respect to VSV-G (**<i>p</i> < 0.01,***<i>p</i> < 0.001, ****<i>p</i> < 0.0001). E. Data from (D) compiled by tropism. Mean ± standard deviation is indicated; one-way ANOVA, <i>p</i> = 0.0002, with Tukey’s Multiple Comparisons Test indicated (**<i>p</i> < 0.01 and ***<i>p</i> < 0.001).</p

Evidence for transmission of proviral genomes from multipotent CD4⁺ HSPCs to differentiated peripheral blood cells.

<p>A. Flow cytometric plots showing purity of CD4-negative lineages containing provirus identical to HSPC-derived provirus. “Pre” indicates the cell population post CD4-bead depletion and prior to fluorescence activated cell sorting (FACS). “Post” indicates the cell populations following FACS. Numbers in the upper right corner indicate the frequency of cells in that quadrant. The frequency of CD4⁺ cells that were also CD3⁺ by gating was 0% (see also <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006509#ppat.1006509.t005" target="_blank">Table 5</a>). B and C. Phylogenetic trees showing genetic relationships amongst amplicons. HIV RNA shown is cell-associated (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006509#ppat.1006509.g010" target="_blank">Fig 10B</a>). Arrows indicate location of identical amplicons shown in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006509#ppat.1006509.g010" target="_blank">Fig 10</a>. Red lines indicate identical sequences. Scale indicates nucleotide substitutions per site. ACH2, 89.6, BaL, YU-2, HXB2 and NL4-3 are subtype B HIVs. 84ZR085 (84ZR) and 94UG114 (94UG) are subtype D HIV molecular clone outgroups [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006509#ppat.1006509.ref032" target="_blank">32</a>]. Phylogenetic analysis was performed by maximum likelihood method using MEGA7[<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006509#ppat.1006509.ref033" target="_blank">33</a>] and history was inferred based on the Hasegawa-Kishino-Yano model [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006509#ppat.1006509.ref034" target="_blank">34</a>]. The tree with the highest log likelihood is shown. Abbreviations: PBMC, unfractionated peripheral blood mononuclear cells; BMMC, bone marrow mononuclear cell (column flow-through).</p