The Impact of COVID-19 on Access to HIV Prevention Services Among Opioid-Dependent Individuals.

The COVID-19 pandemic has necessitated restrictive orders and programmatic changes that may be associated with disruptions in services, including those for opioid-dependent people who inject drugs (PWID). This study aims to assess the impact of COVID-19 pandemic on access to and utilization of various HIV prevention services among PWID with opioid use disorder (OUD). We interviewed 110 PWID enrolled in medication for opioid use disorder (MOUD) treatment (e.g., methadone) between May and October, 2020 to identify if this sample experienced changed in access to the following services due to the COVID-19 pandemic: (a) HIV or sexually transmitted infection (STI) testing, (b) pre-exposure prophylaxis (PrEP) services, (c) HIV counselor or doctor appointments, and (d) clean injection equipment. A majority of the sample reported that COVID-19 had not changed their access to HIV testing or access to STI testing. Almost half of the sample reported that getting an appointment with a doctor decreased due to COVID-19. Participants reported that access to a lab or blood testing, access to injection equipment, and sessions with a case manager or counselor decreased. One-fourth of the 32 participants who were taking PrEP before the onset of COVID-19 reported that they had trouble getting their PrEP prescription due to COVID-19, and some reported that they had difficulty getting the PrEP prescription filled at their pharmacy. Our results indicate that PWID did not experience reduced access to HIV or STI testing, but difficulties in obtaining appointments with HIV counselors or doctors and limited access to PrEP were presented. Innovative strategies are needed to reduce the adverse effects of COVID-19 on HIV prevention among PWID.

Sexuality and aging: Is it time for a new sexual revolution?

People in Western cultures live increasingly longer, and medical advancements, health care availability, and lifestyle changes have widened the possibilities of continued sexuality, sexual activity, and sexual diversity well into older adulthood. Yet, research studies have mainly eschewed discussions of sexual possibilities. Although studies have examined the benefits of sexual activity, often they focus purely on sexual function and sexual dysfunction, physical limitations, and the practicalities (such as finding a partner) of sex as persons age. This commentary posits that, in many instances, the social constraints around aging and sexuality inhibit sexuality in older adults in ways that may be more significant than functional or practical limitations. Portrayals in the media either reinforce social norms of the asexual older adult or portray images of the "sexy oldie" that may be unattainable for many older adults. We provide a brief review of sexuality research and prevailing sexual social norms. As Towler et al.'s (2021) elaborate study illustrates, many sexually active older adults struggle with ageism, stigma, and shame arising from the perceived social unacceptability of their sexuality. Studies of older adults from other Western countries reveal similar stories. Accordingly, achieving sexual well-being may be more dependent on changing social norms around sexuality and aging than on discovering new arousal medication to treat physical limitations. Moreover, we advocate for changing the social and academic dialogue from successful aging, which requires maintaining health and vitality-to the aging experience, which incorporates aspects of positive aging such as sexual wisdom, sexual experience, and the sexual diversity that comes with older adulthood. This "new sexual revolution" would elevate sexuality and aging as socially admirable and desirable.

Pleasure and PrEP: A Systematic Review of Studies Examining Pleasure, Sexual Satisfaction, and PrEP.

Pre-exposure prophylaxis (PrEP) is an effective form of Human Immunodeficiency Virus (HIV) prevention for people at potential risk for exposure. Despite its demonstrated efficacy, PrEP uptake and adherence have been discouraging, especially among groups most vulnerable to HIV transmission. A primary message to persons who are at elevated risk for HIV has been to focus on risk reduction, sexual risk behaviors, and continued condom use, rarely capitalizing on the positive impact on sexuality, intimacy, and relationships that PrEP affords. This systematic review synthesizes the findings and themes from 16 quantitative, qualitative, and mixed methods studies examining PrEP motivations and outcomes focused on sexual satisfaction, sexual pleasure, sexual quality, and sexual intimacy. Significant themes emerged around PrEP as increasing emotional intimacy, closeness, and connectedness; PrEP as increasing sexual options and opportunities; PrEP as removing barriers to physical closeness and physical pleasure; and PrEP as reducing sexual anxiety and fears. It is argued that positive sexual pleasure motivations should be integrated into messaging to encourage PrEP uptake and adherence, as well as to destigmatize sexual pleasure and sexual activities of MSM.

Direct or indirect association in a complex disease: the role of SLC22A4 and SLC22A5 functional variants in Crohn disease.

A common haplotype spanning 250 kb on chromosome 5q31 is strongly associated with Crohn disease (CD). Recently, two functional variants within the SLC22A4 and SLC22A5 genes at this locus (IBD5), L503F (c.1507C > T) and G-207C (c.-207G > C), have been proposed to contribute directly to susceptibility to CD. However, extensive linkage disequilibrium at the IBD5 locus has complicated efforts to distinguish causal variants from association of the general risk haplotype. We genotyped the SLC22A4 and SLC22A5 variants and other polymorphisms across the risk haplotype in four populations of European origin, and applied regression-based haplotype analysis to over 1,200 fully genotyped case-control pairs, modeling case/control status on the presence of one or more SNPs to test for conditional association and to identify risk haplotypes. We found highly significant association of SNPs at the IBD5 locus with Crohn disease in all populations tested. However, the frequencies of L503F and G-207C in individuals who did not carry the general IBD5 risk haplotype were not significantly different in cases and controls, with associated disease odds ratios (ORs) of 0.90 (95% CI, 0.57-1.40) and 0.90 (95% CI, 0.65-1.23), respectively. Haplotype analysis showed that addition of the SLC22A4 and SLC22A5 variants to a null model that included the background risk haplotype did not significantly improve the model fit. In addition to the common risk haplotype, several rare haplotypes had an increased frequency in cases compared to controls. This study suggests that the molecular basis for Crohn disease susceptibility at the IBD5 locus remains to be defined, and highlights the challenge of the identification of causal variants in a complex disease in regions of extensive linkage disequilibrium.

A functional candidate screen for coeliac disease genes.

It is increasingly evident that different inflammatory disorders show some overlap in their pathological features, concurrence in families and individuals, and shared genetic factors. This might also be true for coeliac disease, a chronic inflammatory disorder of the gastrointestinal system, which shares two linkage regions with inflammatory bowel disease: on chromosome 5q31 (CELIAC2 and IBD5) and 19p13 (CELIAC4 and IBD6). We hypothesised that these regions contain genes that contribute to susceptibility to both disorders. The overlapping 5q31 region contains only five positional candidate genes, whereas the overlapping 19p13 region has 141 genes. As the common disease gene probably plays a role in inflammation, we selected five functional candidate genes from the 19p13 region. We studied these 10 positional and functional candidate genes in our Dutch coeliac disease cohort using 44 haplotype tagging single-nucleotide polymorphisms. Two genes from 19p13 showed a small effect on familial clustering: the cytochrome P450 F3 gene CYP4F3 (P(nominal) 0.0375, odds ratio (OR) 1.77) and CYP4F2 (P(nominal) 0.013, OR 1.33). CYP4F3 and CYP4F2 catalyse the inactivation of leukotriene B4 (LTB4), a potent mediator of inflammation responsible for recruitment and activation of neutrophils. The genetic association of LTB4-regulating gene variants connects the innate immune response of neutrophil mobilisation with that of the established Th1 adaptive immunity present in coeliac disease patients. The findings in coeliac disease need to be replicated. Expanding genetic association studies of these cytochrome genes to other inflammatory conditions should reveal whether their causative influence extends beyond coeliac disease.

Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19.

Evidence from four independent linkage studies and two meta-analyses of genome-wide data support the existence of a locus conferring susceptibility to inflammatory bowel diseases (IBD) in chromosomal region 19p. Identification of a susceptibility allele in this approximately 28.5 Mb region with over 600 genes is a formidable task. To tackle this problem, we undertook two approaches: (1) haplotype-based candidate-gene screen, and (2) evaluation of previously reported associations. For the former, we selected genes with potential implication in IBD pathogenesis based on published functional and expression data, typed SNPs, constructed haplotypes, screened for association in 180 IBD trios, and followed up preliminary associations in 343 IBD patients and 207 control individuals. Overall, we analyzed 465 SNPs, and 260 haplotypes distributed across 56 candidate genes. We found suggestive evidence of association (nominal P<0.01) with four genes (C3, FCER2, IL12RB1, and CRLF1) in a screening stage, but were unable to confirm these preliminary observations at follow-up. In the second approach, we typed four nonsynonymous polymorphisms in genes C3 (R102G and L314P) and ICAM1 (G241R and K469E) in four independent cohorts totaling 2178 IBD cases. We evaluated these data together with previously published reports for three of these variants (C3-Gly102, ICAM1-Arg241, and ICAM1-Glu469), in a meta-analysis. Our pooled meta-analysis provides compelling evidence against association of these variants with disease. Overall, we performed the most comprehensive candidate-gene association study for IBD to date. The information hereby generated constitutes a valuable resource to investigate other common genetic immune diseases, such as celiac disease.

Genetic variation in myosin IXB is associated with ulcerative colitis.

BACKGROUND & AIMS: Common germline genetic variation in the 3' region of myosin IXB (MYO9B) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease. METHODS: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3' region of MYO9B. These included the strongest celiac disease-associated variants reported in a Dutch cohort. These SNPs were studied in 3 independently collected and genotyped case-control cohorts of European descent (UK, Dutch, and Canadian/Italian), comprising in total 2717 inflammatory bowel disease patients (1197 with Crohn's disease, 1520 with ulcerative colitis) and 4440 controls. RESULTS: Common variation in MYO9B was associated with susceptibility to inflammatory bowel disease in all 3 cohorts examined (most associated SNP, rs1545620; meta-analysis P = 1.9 x 10(-6); odds ratio, 1.2), with the same alleles showing association as reported for celiac disease. CONCLUSIONS: MYO9B genetic variants predispose to inflammatory bowel disease. Interestingly, rs1545620 is a nonsynonymous variant leading to an amino acid change (Ala1011Ser) in the third calmodulin binding IQ domain of MYO9B. Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MYO9B was considerably stronger with ulcerative colitis, although weaker association with Crohn's disease also was observed. These data imply shared causal mechanisms underlying intestinal inflammatory diseases.