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Background Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with human immunodeficiency virus (HIV), who have heightened immune activation and cardiovascular risks. Methods Among 609 postmenopausal women (1234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis: carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004–2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. Results Women (mean age, 51 years; 80% HIV positive) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never-users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI},.40–.80]; P <.01), 2.51 µm less progression of CIMT per year (95% CI, –4.60, to –.41; P =.02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI,.14–1.03; P =.06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. Conclusions HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low. [ABSTRACT FROM AUTHOR]

Introduction: Lifestyle improvements are key modifiable risk factors for Type 2 diabetes mellitus (DM) however specific influences of biologically active dietary metabolites remain unclear. Our objective was to compare non-targeted plasma metabolomic profiles of women with versus without confirmed incident DM. We focused on three lipid classes (fatty acyls, prenol lipids, polyketides). Materials and methods: Fifty DM cases and 100 individually matched control participants (80% with human immunodeficiency virus [HIV]) were enrolled in a case-control study nested within the Women's Interagency HIV Study. Stored blood samples (1–2 years prior to DM diagnosis among cases; at the corresponding timepoint among matched controls) were assayed in triplicate for metabolomics. Time-of-flight liquid chromatography mass spectrometry with dual electrospray ionization modes was utilized. We considered 743 metabolomic features in a two-stage feature selection approach with conditional logistic regression models that accounted for matching strata. Results: Seven features differed by DM case status (all false discovery rate-adjusted q<0.05). Three flavonoids (two flavanones, one isoflavone) were respectively associated with lower odds of DM (all q<0.05), and sorbic acid was associated with greater odds of DM (all q<0.05). Conclusion: Flavonoids were associated with lower odds of incident DM while sorbic acid was associated with greater odds of incident DM. [ABSTRACT FROM AUTHOR]

Background: U.S. women who have been incarcerated report high rates of sexual risk behavior and sexually transmitted infections (STIs). Materials and Methods: We estimated the effect of incarceration on the time to first incident STI in a multicenter cohort of U.S. women with or at risk for HIV. We used marginal structural models to compare time to first self-reported gonorrhea, chlamydia, or trichomonas infection for nonincarcerated women and incarcerated women. Covariates included demographic factors, HIV status, sex exchange, drug/alcohol use, and prior incarceration. Results: Three thousand hundred twenty-four women contributed a median of 4 at-risk years and experienced 213 first incident STI events. The crude incidence of STIs was 3.7 per 100 person-years for incarcerated women and 1.9 per 100 person-years for nonincarcerated women. The weighted hazard ratio for incident STIs was 4.05 (95% confidence interval: 1.61–10.19). Conclusion: Women with or at risk for HIV in the United States who have recently experienced incarceration may be at increased STI risk. [ABSTRACT FROM AUTHOR]

Summary: In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression.Background: Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women.Methods: Among 606 women with HIV in the Women's Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and nonactivation/normal function (%CD57-CD28+) with natural-cause, HIV-related, and non-HIV-related mortality.Results: At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors.Conclusions: Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression. [ABSTRACT FROM AUTHOR]

Background: Characterizing estradiol among women with HIV may have implications for breast cancer and cardiovascular disease risk but has not been adequately explored. We quantified differences in total (E2), free (FE2) estradiol, and sex hormone binding globulin (SHBG) by HIV and viral suppression status. Methods: Women from a substudy (2003–2006) within the Women's Interagency HIV Study (IRB approved at each participating site) were included if they reported: a period in the last six months, were not pregnant/breastfeeding, no oophorectomy, and no exogenous hormone use in the prior year. Serum was collected on days 2–4 of the menstrual cycle. We assessed differences in biomarkers at 25th, 50th, and 75th percentiles by HIV and viral suppression status using weighted quantile regression. Results: Among 643 women (68% with HIV) median age was 37 years. All E2 percentiles were significantly (p < 0.05) lower in women with suppressed viral load versus women without HIV (4–10 pg/mL). The 25th and 50th percentile of E2 were 4–5 pg/mL lower in women with unsuppressed viral load compared to women without HIV (p < 0.05). The 25th and 50th percentile of SHBG was significantly higher in women with unsuppressed viral load compared to women without HIV (10 and 12 nmol/L, respectively). There were no consistent differences in estradiol or SHBG by suppression status. Conclusions: There were no differences in FE2 but significantly lower E2 and higher SHBG among women with HIV versus without HIV. Further research is merited in a large contemporary sample to clarify the clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Background: Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown.Methods: In 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1) were measured at 674 person-visits spanning ≤2 years.Results: Menopause (post- vs premenopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (β = 161.89 ng/mL; 95% confidence interval [CI], 18.37-305.41 and 65.48 ng/mL, 95% CI, 6.64-124.33, respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI, 16.63-484.79; P = .04), but not in premenopausal or postmenopausal periods.Conclusions: In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during menopausal transition warrant further investigation. [ABSTRACT FROM AUTHOR]

Trust in providers and health care systems (HCSs) has been associated with higher HIV antiretroviral (ART) adherence; however, most previous studies enrolled primarily men and did not concurrently assess provider trust, HCS distrust, and clinical/biological outcomes. We enrolled 239 Washington, DC Women's Interagency HIV Study (WIHS) women: 167 with HIV (WWH) and 72 without HIV. In 2006 and 2017–2018, women completed surveys on provider trust and HCS distrust. Clinical, social, and demographic covariates were obtained during the 2017–2018 WIHS study visit. Descriptive analyses included chi-squared and Mann–Whitney tests. Wilcoxon signed-rank tests assessed trust measure change over time. Logistic (provider trust) and linear (HCS distrust) models were constructed in R. The majority of women were African American/Black (76.9%) with a median age of 52 (interquartile range 48, 58) and currently insured (99.6%). In multi-variable analyses, women with HIV (WWH) had higher odds of high provider trust [adjusted odds ratio (aOR) 2.90, 95% confidence interval (CI) 1.34, 6.45], with ≥95% ART adherence associated with high provider trust among only WWH (aOR 4.13, 95% CI 1.14, 15.92). Multi-variable models also showed 3.40-point higher HCS distrust scores among WWH who reported ≥95% ART adherence (p = 0.03). CD4 count and HIV viral load were not associated with provider trust or HCS distrust. Provider (p = 0.67) and HCS (p = 0.65) trust did not significantly change in this population at two time points for 10 years. Self-reported antiretroviral therapy adherence significantly associated with high provider trust, yet also with high HCS distrust, revealing a nuanced relationship to providers and the HCS among WWH. [ABSTRACT FROM AUTHOR]

Background: To estimate the incidence, prevalence, frequency, and duration of incarceration and to identify risk factors for incarceration among women at risk for human immunodeficiency virus (HIV) in the United States. Methods: During semiannual study visits in a multicenter cohort study, 970 HIV sero-negative participants at risk for HIV were asked about their own incarceration (10/2007–09/2017) and incarceration of sexual partners (10/2013–09/2017). We used descriptive statistics and multivariable log-binomial regression to identify baseline predictors of incident incarceration. Results: Median follow-up time across the 970 participants was 5.5 years (IQR 3.5–9.5). Nearly half (n = 453, 46.7%) of participants were incarcerated during or before the study, and the incarceration rate was 5.5 per 100 person-years. In multivariable models, incident incarceration was associated with prior incarceration (RR 5.20, 95% CI: 3.23–8.41) and noninjection drug use (RR 1.57, 95% CI: 1.10–2.25). Conclusions: Incarceration is common for women at risk for HIV. Prevention interventions that address the complex interplay of drug use, sex exchange, and housing instability for women who have experienced incarceration have the potential to reach an important group of U.S. women at risk of HIV infection. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or infections.Methods: We conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA).Results: There was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4+ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8+ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4+ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8+ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24-108 years; P = .001).Conclusions: Despite antiretroviral therapy-associated improvement in CD4+ T-cell counts (nadir, <200/μL; >350/μL after antiretroviral therapy), antigen-specific CD4+ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed. [ABSTRACT FROM AUTHOR]

Objective s. To examine whether women's incarceration increases numbers of total and new sexual partners. Methods. US women with or at risk for HIV in a multicenter cohort study answered incarceration and sexual partner questions semiannually between 2007 and 2017. We used marginal structural models to compare total and new partners at visits not following incarceration with all visits following incarceration and visits immediately following incarceration. Covariates included demographics, HIV status, sex exchange, drug or alcohol use, and housing instability. Results. Of the 3180 participants, 155 were incarcerated. Women reported 2 partners, 3 or more partners, and new partners at 5.2%, 5.2%, and 9.3% of visits, respectively. Relative to visits not occurring after incarceration, odds ratios were 2.41 (95% confidence interval [CI] = 1.20, 4.85) for 2 partners, 2.03 (95% CI = 0.97, 4.26) for 3 or more partners, and 3.24 (95% CI = 1.69, 6.22) for new partners at visits immediately after incarceration. Odds ratios were similar for all visits following incarceration. Conclusions. Women had more total partners and new partners immediately and at all visits following incarceration after confounders and loss to follow-up had been taken into account. [ABSTRACT FROM AUTHOR]

Background: Understanding factors associated with contraceptive use post-abortion can inform clinical practices to improve contraception uptake. Materials and Methods: This prospective cohort study included adult women who completed the survey before surgical abortion at an Atlanta, Georgia clinic, with an online survey 12 weeks later. Poisson regression models assessed associations between demographic and reproductive factors and use of more effective (contraceptive pill, ring, patch, injectables, intrauterine device [IUD], implant, sterilization) versus less effective (none, condoms, withdrawal, rhythm methods) contraception at follow-up. Results: Three hundred ninety three women completed the initial survey; 180 (46%) completed follow-up. Of those completing follow-up, 109 (61%) expressed interest in initiating more effective methods in-clinic, yet only 85 (47%) reported using these methods at follow-up. Sixty-one women (34%) were not using their preferred contraceptive at follow-up; 34 (56%) of whom preferred to use IUD, implant, or sterilization. More effective contraception use was significantly associated with age over 30 (adjusted risk ratio, aRR 1.71, 95% confidence interval (CI): 1.14–2.57); nulliparity (aRR 1.70, 95% CI: 1.20–2.42); use of more effective methods at most recent conception (aRR 2.56, 95% CI: 1.73–3.79); interest in more effective methods at the time of the abortion (aRR 1.55, 95% CI: 1.11–2.18); and receiving a contraceptive/prescription at the time of abortion (aRR 1.97, 95% CI: 1.37–2.81). Conclusions: Over half of women use less effective contraception 3 months post-abortion, despite a high interest in more effective contraception. Additional research is needed to understand contraceptive decision making in the context of abortion care to inform interventions to increase contraceptive uptake. [ABSTRACT FROM AUTHOR]

During quorum sensing in the plant pathogen Pantoea stewartii subsp. stewartii, EsaI, an acyl-homoserine lactone (AHL) synthase, and the transcription factor EsaR coordinately control capsular polysaccharide production. The capsule is expressed only at high cell density when AHL levels are high, leading to inactivation of EsaR. In lieu of detailed structural information, the precise mechanism whereby EsaR recognizes AHL and is hindered by it, in a response opposite to that of most other LuxR homologues, remains unresolved. Hence, a random mutagenesis genetic approach was designed to isolate EsaR* variants that are immune to the effects of AHL. Error-prone PCR was used to generate the desired mutants, which were subsequently screened for their ability to repress transcription in the presence of AHL. Following sequencing, site-directed mutagenesis was used to generate all possible mutations of interest as single, rather than multiple amino acid substitutions. Eight individual amino acids playing a critical role in the AHL-insensitive phenotype have been identified. The ability of EsaR* variants to bind AHL and the effect of individual substitutions on the overall conformation of the protein were examined through in vitro assays. Six EsaR* variants had a decreased ability to bind AHL. Fluorescence anisotropy was used to examine the relative DNA binding affinity of the final two EsaR* variants, which retained some AHL binding capability but remained unresponsive to it, perhaps due to an inability of the N-terminal domain to transduce information to the C-terminal domain. [ABSTRACT FROM AUTHOR]