Racial differences in α4β7 expression on CD4+ T cells of HIV-negative men and women who inject drugs.
Ontology highlight
ABSTRACT: Introduction
We performed a cross-sectional study of HIV-uninfected men and women who inject drugs from the ALIVE cohort to examine if black men and women who inject drugs have higher levels of CD4+ T cells expressing the integrin heterodimer α4β7 compared to white men and women.Materials and methods
Flow cytometry was used to examine expression of α4β7 and other markers associated with different functional CD4+ T cell subsets in both men and women who inject drugs.Results
Higher levels of α4β7, CCR5, and CCR6 were observed on CD4+ T cells from black participants compared with white participants. In a multivariable model, α4β7 expression differed by race, but not sex, age, or other factors.Discussion
Black men and women express higher percentages of α4β7 expressing CD4+ T cells, which may play a role in HIV disease.
SUBMITTER: Martin AR
PROVIDER: S-EPMC7447027 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Racial differences in α4β7 expression on CD4+ T cells of HIV-negative men and women who inject drugs.
Martin Alyssa R AR Sivro Aida A Packman Zoe R ZR Patel Eshan U EU Goes Livia R LR McKinnon Lyle R LR Astemborski Jacquie J Kirk Gregory D GD Mehta Shruti H SH Cicala Claudia C Arthos James J Redd Andrew D AD Quinn Thomas C TC
PloS one 20200825 8
<h4>Introduction</h4>We performed a cross-sectional study of HIV-uninfected men and women who inject drugs from the ALIVE cohort to examine if black men and women who inject drugs have higher levels of CD4+ T cells expressing the integrin heterodimer α4β7 compared to white men and women.<h4>Materials and methods</h4>Flow cytometry was used to examine expression of α4β7 and other markers associated with different functional CD4+ T cell subsets in both men and women who inject drugs.<h4>Results</h ...[more]
Similar Datasets
Project description:Backgroundα4β7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of α4β7 expressing CD4+ T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown if this phenomenon is also observed in men who have sex with men (MSM) or people who inject drugs (PWID).MethodsMSM and transgender women who seroconverted as part of the HVTN 505 HIV vaccine trial and PWID who seroconverted during the ALIVE cohort study were selected as cases and matched to HIV-uninfected controls from the same studies (1:1 and 1:3, respectively). Pre-seroconversion PBMC samples from cases and controls in both studies were examined by flow cytometry to measure levels of α4β7 expression on CD4+ T cells. Multivariable conditional logistic regression was used to compare α4β7 expression levels between cases and controls. A Kaplan-Meier curve was used to examine the association of α4β7 expression pre-seroconversion with HIV disease progression.FindingsIn MSM and transgender women (n = 103 cases, 103 controls), there was no statistically significant difference in the levels of α4β7 expression on CD4+ T cells between cases and controls (adjusted odds ratio [adjOR] =1.10, 95% confidence interval [CI]=0.94,1.29; p = 0.246). Interestingly, in PWID (n = 49 cases, 143 controls), cases had significantly lower levels of α4β7 expression compared to their matched controls (adjOR = 0.80, 95% CI = 0.68, 0.93; p = 0.004). Among HIV-positive PWID (n = 47), there was no significant association in HIV disease progression in individuals above or below the median level of α4β7 expression (log-rank p = 0.84).InterpretationIn contrast to findings in heterosexual women, higher α4β7 expression does not predict HIV acquisition or disease progression in PWID or MSM.FundingThis study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. The study was also supported by extramural grants from NIAID T32AI102623 (E.U.P.), and UM1AI069470.
| S-EPMC7658649 | biostudies-literature
Project description:Injection drug use is prevalent in northwestern Bangladesh. We sought to explore the context of needle/syringe sharing among persons who inject drugs (PWID), examining risk exposures to blood-borne infections like the human immunodeficiency virus (HIV) and hepatitis in a region where these dual epidemics are likely to expand.We used a qualitative research approach to learn about injection practices, conducting 60 in-depth interviews among PWID. We then conducted 12 focus group discussions (FGDs) that generated a checklist of salient issues, and followed up with personal observations of typical days at the drug-use venues. Content and interpretative frameworks were used to analyze qualitative information and socio-demographic information, using SPSS software.We found that needle/syringe-sharing behaviours were integrated into the overall social and cultural lives of drug users. Sharing behaviours were an central component of PWID social organization. Sharing was perceived as an inherent element within reciprocal relationships, and sharing was tied to beliefs about drug effects, economic adversity, and harassment due to their drug user status. Carrying used needles/syringes to drug-use venues was deemed essential since user-unfriendly needle-syringe distribution schedules of harm reduction programmes made it difficult to access clean needles/syringes in off-hours. PWID had low self-esteem. Unequal power relationships were reported between the field workers of harm reduction programmes and PWID. Field workers expressed anti-PWID bias and judgmental attitudes, and also had had misconceptions about HIV and hepatitis transmission. PWID were especially disturbed that no assistance was forthcoming from risk reduction programme staff when drug users manifested withdrawal symptoms.Interventions must take social context into account when scaling up programmes in diverse settings. The social organization of PWID include values that foster needle-syringe sharing. Utilization and impact of risk reduction programmes might be improved with expanded clean needle/syringe distribution at times and venues convenient for PWID, better trained and non-judgmental staff, and medical assistance for health problems, including drug withdrawal symptoms.
| S-EPMC4743837 | biostudies-other
Project description:BackgroundTo achieve elimination of hepatitis C virus (HCV) infection, limited resources can be best allocated through estimation of "care cascades" among groups disproportionately affected. In San Francisco and elsewhere, these groups include young (age ≤ 30 years) people who inject drugs (YPWID), men who have sex with men who inject drugs (MSM-IDU), and low-income trans women.MethodsWe developed cross-sectional HCV care cascades for YPWID, MSM-IDU, and trans women using diverse data sources. Population sizes were estimated using an inverse variance-weighted average of estimates from the peer-reviewed literature between 2013 and 2019. Proportions of past/current HCV infection, diagnosed infection, treatment initiation, and evidence of cure (sustained virologic response at 12 weeks posttreatment) were estimated from the literature using data from 7 programs and studies in San Francisco between 2015 and 2020.ResultsThe estimated number of YPWID in San Francisco was 3748; 58.4% had past/current HCV infection, of whom 66.4% were diagnosed with current infection, 9.1% had initiated treatment, and 50% had confirmed cure. The corresponding figures for the 8135 estimated MSM-IDU were: 29.4% with past/current HCV infection, 70.3% diagnosed with current infection, 28.4% initiated treatment, and 38.9% with confirmed cure. For the estimated 951 low-income trans women, 24.8% had past/current HCV infection, 68.9% were diagnosed with current infection, 56.5% initiated treatment, and 75.5% had confirmed cure.ConclusionsIn all 3 populations, diagnosis rates were relatively high; however, attention is needed to urgently increase treatment initiation in all groups, with a particular unmet need among YPWID.
| S-EPMC8442786 | biostudies-literature
Project description:BackgroundHIV infection is common among people who inject drugs (PWID), and HIV-positive PWID may be particularly vulnerable to depression. This study measured the prevalence of depressive symptoms and the factors associated with severe symptoms among 455 HIV-positive PWID in Thai Nguyen, Vietnam.MethodsWe used cross-sectional data from PWID in a randomized controlled trial of an intervention to reduce high-risk injecting and sexual behaviors in Thai Nguyen from 2009-2013. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). We used logistic regression to assess demographic, clinical, and psychosocial predictors of severe depressive symptoms (CES-D≥23) with prevalence odds ratios (POR) and 95% confidence intervals (CI).ResultsThe prevalence of severe depressive symptoms (CES-D≥23) was 44%. 25% of participants had mild to moderate depressive symptoms (16≤CES-D<23), and 31% experienced no depressive symptoms (CES-D<16). Not being married, self-rated poor health, greater frequency of injection drug use, history of overdose, no alcohol use, and daily cigarette smoking were positively associated with severe depressive symptoms in unadjusted models and remained predictive in a multivariable model. The strongest predictors of depressive symptoms were self-reported poor health (POR = 2.94, 95% CI: 1.82, 4.76), no current alcohol use (POR = 2.35, 95% CI: 1.47, 3.77), and not currently married or cohabitating (POR = 2.21, 95% CI = 1.40, 3.47).ConclusionSevere depressive symptoms were common among HIV-positive PWID in Thai Nguyen and were strongly associated with demographic, clinical, and psychosocial factors. Interventions that promote social support from family and reduce drug dependence may particularly benefit PWID experiencing severe depressive symptoms. Greater recognition and treatment of depressive symptoms has the potential to enhance quality of life and improve HIV clinical outcomes for PWID.
| S-EPMC5783407 | biostudies-literature
Project description:BackgroundWomen who inject drugs and who also exchange sex are at increased risk for HIV infection, but data on this population in the United States remain sparse.MethodsThis study assessed the prevalence of exchanging sex for money or drugs among women who inject drugs using data from the 2009 US National HIV Behavioral Surveillance (NHBS) system. Prevalence of being HIV-positive (testing positive in NHBS), HIV-positive-unaware (reporting being HIV-negative or unknown status but testing positive in NHBS), and risk behaviors and use of services were compared between women who did and did not exchange sex. The association between exchange sex and being HIV-positive-unaware of the infection was examined using multivariate Poisson models with robust standard errors.ResultsAmong 2305 women who inject drugs, 39% reported receiving things like money or drugs from ≥1 male partners in exchange for oral, vaginal, or anal sex in the previous 12 months. Women who exchanged sex were more likely to be unemployed, homeless, lack health insurance, have multiple condomless vaginal or anal sex partners, and receptively share syringes. In multivariate analysis, exchange sex was associated with being HIV-positive-unaware (adjusted prevalence ratio 1.97, 95% confidence intervals: 1.31 to 2.97).ConclusionsPrevalence of exchange sex was high in this population. Women who exchange sex were more likely to be socially disadvantaged, report sexual and injection risk, and be HIV-positive-unaware. They represent an important group to reach with HIV prevention, testing, and care services.
| S-EPMC5681711 | biostudies-literature
Project description:ImportanceIn the US and Canada, women comprise approximately one-third of people who inject drugs (PWID); however, clinical characteristics and outcomes of injection drug use complications in women are poorly described.ObjectiveTo identify clinical characteristics and outcomes of infective endocarditis (IE) among women who inject drugs (WWID).Design, setting, and participantsThis is a retrospective cohort study of PWID with definite IE (per 2023 Duke-International Society for Cardiovascular Infectious Diseases criteria) admitted from April 5, 2007, to March 15, 2018, at 5 tertiary-care hospitals in London, Ontario, and Regina, Saskatchewan, Canada. Data were analyzed from June 1, 2023, to August 2, 2024. Descriptive analyses were conducted for baseline characteristics at index hospitalization and stratified by sex.Main outcomes and measuresThe primary outcome was the difference in 5-year survival between female and male PWID with IE. The secondary outcome was 1-year survival. Multivariable time-dependent Cox proportional hazards regression analyses were conducted for variables of clinical importance to evaluate 5-year mortality.ResultsOf 430 PWID with IE, 220 (51.2%) were women; of 332 non-PWID with IE, 101 (30.4%) were women. WWID with IE were younger than men (median [IQR] age, 31.5 [27.0-38.5] vs 38.5 [31.0-49.0] years), and 11 of 220 (5.0%) were pregnant at index hospitalization, although only 12 of 220 (5.5%) had contraceptive use documented. Women had a larger proportion of right-sided IE than men (158 of 220 women [71.8%] vs 113 of 210 men [53.8%]). WWID living in urban areas had higher mortality than WWID in rural areas (adjusted hazard ratio [aHR], 2.70; 95% CI, 1.15-6.34; P = .02). Overall mortality was lower among PWID referred for substance use disorder counseling in centers with inpatient services compared with centers with only outpatient referrals (aHR, 0.29; 95% CI, 0.17-0.51; P < .001). Overall mortality was lower with right-sided heart disease for both women (aHR, 0.44; 95% CI, 0.27-0.71; P < .001) and men (aHR, 0.22; 95% CI, 0.10-0.50; P < .001) and was higher with congestive heart failure for both women (aHR, 2.32; 95% CI, 1.29-4.18; P = .005) and men (aHR, 1.73; 95% CI, 1.07-2.79; P = .02).Conclusions and relevanceIn this cohort of PWID with IE, women were overrepresented. Reasons for women's disproportionately high IE incidence need further study. Inpatient substance use disorder services, contraception counseling, and enhanced social support for WWID living in urban areas need to be prioritized.
| S-EPMC11452813 | biostudies-literature
Project description:BackgroundHIV prevention interventions in the United States have failed to eliminate racial inequities. Here, we evaluate factors associated with racial inequities in HIV prevalence among people who inject drugs using HIV Prevention Trial Network 037 data.MethodsWe measured racial homophily (ie, all members share the same race), being in an HIV+ network (network with ≥1 HIV+ member), and drug and sex risk behaviors. A 2-level logistic regression with a random intercept evaluated the association between being in an HIV+ network and race adjusting for individual-level and network-level factors.ResultsData from 232 index participants and 464 network members were included in the analysis. Racial homophily was high among blacks (79%) and whites (70%); 27% of all-black, 14% of all-white, and 23% of racially mixed networks included HIV+ members. Sex risk was similar across networks, but needle sharing was significantly lower in all-black (23%) compared with all-white (48%) and racially mixed (46%) networks. All-black [adjusted odds ratio (AOR), 3.6; 95% confidence interval (CI), 1.4 to 9.5] and racially mixed (AOR, 2.0; 95% CI: 1.1 to 3.7) networks were more likely to include HIV+ network members; other factors associated with being in HIV+ network included homelessness (AOR, 2.0; 95% CI, 1.2 to 3.2), recent incarceration (AOR, 0.4; 95% CI, 0.2 to 0.7), and cocaine injection (AOR, 1.7; 95% CI, 1.0 to 2.7). Risk behaviors were not associated with being in an HIV+ network.ConclusionDespite having lower drug risk behavior, all-black networks disproportionately included HIV+ members. HIV prevention interventions for people who inject drugs need to go beyond individual risk and consider the composition of risk networks.
| S-EPMC5884106 | biostudies-literature
Project description:AimsThe Ethnic Minority Meta-Analysis (EMMA) aims to assess racial/ethnic disparities in HIV infection among people who inject drugs (PWID) across various countries. This is the first report of the data.MethodsStandard systematic review/meta-analysis methods were utilized, including searching for, screening and coding published and unpublished reports and meta-analytical statistics. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for reporting methods. Disparities were measured with the odds ratio (OR) for HIV prevalence among ethnic minority PWID compared to ethnic majority PWID; an OR >1.0 indicated higher prevalence among ethnic minorities.ResultsRacial/ethnic disparities in HIV prevalence among PWID were examined in 131 prevalence reports, with 214 racial/ethnic minority to majority comparisons, comprising 106 715 PWID. Overall, the pooled OR indicates an increased likelihood of higher HIV prevalence among racial/ethnic minority compared to racial/ethnic majority PWID [OR = 2.09, 95% confidence interval (CI): 1.92-2.28]. Among 214 comparisons, 106 produced a statistically significant higher OR for minorities; in 102 comparisons the OR was not significantly different from 1.0; six comparisons produced a statistically significant higher OR for majority group members. Disparities were particularly large in the United States, pooled OR = 2.22 (95% CI: 2.03-2.44). There was substantial variation in ORs-I(2) = 75.3%: interquartile range = 1.38-3.56-and an approximate Gaussian distribution of the log ORs.ConclusionsAmong people who inject drugs, ethnic minorities are approximately twice as likely to be HIV seropositive than ethnic majorities. The great heterogeneity and Gaussian distribution suggest multiple causal factors and a need to tailor interventions to local conditions.
| S-EPMC3504180 | biostudies-literature
Project description:HIV infects and replicates in CD4+ T cells but effects on host immunity and disease also involve depletion, hyper-activation, and modification of CD4-negative cell populations. In particular, the depletion of CD4-negative γδ T cells is common to all HIV+ individuals. We found that soluble or cell-associated envelope glycoproteins from CCR5-tropic strains of HIV could bind, activates the p38-caspase pathway, and induce the death of γδ cells. Envelope binding requires integrin α4β7 and chemokine receptor CCR5 which are at high levels and form a complex on the γδ T cell membrane. This receptor complex facilitated V3 loop binding to CCR5 in the absence of CD4-induced conformational changes. Cell death was increased by antigen stimulation after exposure to envelope glycoprotein. Direct signaling by envelope glycoprotein killed CD4-negative γδ T cells and reproduced a defect observed in all patients with HIV disease.
| S-EPMC3228498 | biostudies-literature
Project description:Systemic arterial hypertension is an important cause of cardiovascular disease morbidity and mortality. African Americans are disproportionately affected by hypertension, in fact the incidence, prevalence, and severity of hypertension is highest among African American (AA) women. Previous data suggests that differential gene expression influences individual susceptibility to selected diseases and we hypothesized that this phenomena may affect health disparities in hypertension. Transcriptional profiling of peripheral blood mononuclear cells from AA or white, normotensive or hypertensive females identified thousands of mRNAs differentially-expressed by race and/or hypertension. Predominant gene expression differences were observed in AA hypertensive females compared to AA normotensives or white hypertensives. Since microRNAs play important roles in regulating gene expression, we profiled global microRNA expression and observed differentially-expressed microRNAs by race and/or hypertension. We identified novel mRNA-microRNA pairs potentially involved in hypertension-related pathways and differently-expressed, including MCL1/miR-20a-5p, APOL3/miR-4763-5p, PLD1/miR-4717-3p, and PLD1/miR-4709-3p. We validated gene expression levels via RT-qPCR and microRNA target validation was performed in primary endothelial cells. Altogether, we identified significant gene expression differences between AA and white female hypertensives and pinpointed novel mRNA-microRNA pairs differentially-expressed by hypertension and race. These differences may contribute to the known disparities in hypertension and may be potential targets for intervention. This SuperSeries is composed of the SubSeries listed below. This SuperSeries is composed of the SubSeries listed below.
2016-11-16 | GSE75672 | GEO