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Improving patient engagement in HIV care is critical for maximizing the impact of antiretroviral therapy (ART). We conducted a systematic review of studies that used HIV-positive peers to bolster linkage, retention, and/or adherence to ART. We searched articles published and indexed in Pubmed, PsycINFO, and CINAHL between 1996 and 2014. Peers were required to be HIV-positive. Studies were restricted to those published in English. Nine studies with n = 4658 participants met the inclusion criteria. Peer-based interventions were predominantly focused on improving adherence to ART, or evaluations of retention and adherence via viral suppression. Five (56 %) were conducted in sub-Saharan Africa. Overall findings were mixed on the impact of peers on ART adherence, viral suppression, and mortality. While positive effects of peer interventions on improving linkage and retention were found, there were limited studies assessing these outcomes. Additional research is warranted to demonstrate the impact of peers on linkage and retention in diverse populations.

Introduction: Acceptability and willingness to both take and pay for HIV self‐tests (HIVSTs) in US neighbourhoods with high rates of HIV infection are not well understood. Methods: We surveyed 1,535 individuals about acceptability and willingness to take and pay for an HIVST in a predominately African American neighbourhood with 3% HIV seroprevalence. We recruited individuals presenting for HIV screening services in a community‐based programme. Latent class analysis (LCA) grouped individuals with similar patterns of HIV‐risk behaviours and determined which groups would be most willing to use and buy HIVSTs. Results: Nearly 90% of respondents were willing to use an HIVST; 55% were willing to buy HIVSTs, but only 23% were willing to pay the market price of US$40. Four distinct groups emerged and were characterized by risk behaviours: (1) low risk (N = 324); (2) concurrent partnerships (N = 346); (3) incarceration and substance use (N = 293); and (4) condomless sex/multiple partners (N = 538). Individuals in the low‐risk class were less willing to self‐test compared to concurrent sexual partners (OR = 0.39, p = .003) and incarceration and substance use (OR = 0.46, p = .011) classes. There were no significant differences across classes in the amount individuals were willing to pay for an HIVST. Conclusions: HIVSTs were overwhelmingly acceptable but cost prohibitive; most participants were unwilling to pay the market rate of US $ 40. Subsidizing and implementing HIVST programmes in communities with high rates of infection present a public health opportunity, particularly among individuals reporting condomless sex with multiple partners, concurrent sexual partnerships and those with incarceration and substance use histories.

Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic 1 – 4 . Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen ( HLA ) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort ( n  = 1,428) comprised unvaccinated individuals who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci with disease course and identified a strong association between HLA-B*15:01 and asymptomatic infection, observed in two independent cohorts. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal structure of HLA-B*15:01–peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01 -mediated pre-existing immunity. The human leukocyte antigen allele HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection due to pre-existing T cell immunity.

Adaptive modifications of heteromeric proteins may involve genetically based changes in single subunit polypeptides or parallel changes in multiple genes that encode distinct, interacting subunits. Here we investigate these possibilities by conducting a combined evolutionary and functional analysis of duplicated globin genes in natural populations of deer mice (Peromyscus maniculatus) that are adapted to different elevational zones. A multilocus analysis of nucleotide polymorphism and linkage disequilibrium revealed that high-altitude adaptation of deer mouse hemoglobin involves parallel functional differentiation at multiple unlinked gene duplicates: two α-globin paralogs on chromosome 8 and two β-globin paralogs on chromosome 1. Differences in O₂-binding affinity of the alternative β-chain hemoglobin isoforms were entirely attributable to allelic differences in sensitivity to 2,3-diphosphoglycerate (DPG), an allosteric cofactor that stabilizes the low-affinity, deoxygenated conformation of the hemoglobin tetramer. The two-locus β-globin haplotype that predominates at high altitude is associated with suppressed DPG-sensitivity (and hence, increased hemoglobin-O₂ affinity), which enhances pulmonary O₂ loading under hypoxia. The discovery that allelic differences in DPG-sensitivity contribute to adaptive variation in hemoglobin-O₂ affinity illustrates the value of integrating evolutionary analyses of sequence variation with mechanistic appraisals of protein function. Investigation into the functional significance of the deer mouse β-globin polymorphism was motivated by the results of population genetic analyses which revealed evidence for a history of divergent selection between elevational zones. The experimental measures of O₂-binding properties corroborated the tests of selection by demonstrating a functional difference between the products of alternative alleles.

Abstract Emerging evidence suggests that diet, particularly one that is rich in dietary fiber, may prevent the progression of chronic kidney disease (CKD) and its associated complications in people with established CKD. This narrative review summarizes the current evidence and discusses the opportunities for increasing fiber intake in people with CKD to improve health and reduce disease complications. A higher consumption of fiber exerts multiple health benefits, such as increasing stool output, promoting the growth of beneficial microbiota, improving the gut barrier and decreasing inflammation, as well decreasing uremic toxin production. Despite this, the majority of people with CKD consume less than the recommended dietary fiber intake, which may be due in part to the competing dietary potassium concern. Based on existing evidence, we see benefits from adopting a higher intake of fiber-rich food, and recommend cooperation with the dietitian to ensure an adequate diet plan. We also identify knowledge gaps for future research and suggest means to improve patient adherence to a high-fiber diet.