Improvements in Virologic Control Among PWH Over Time: Narrowing the Gap Between Those With and Without STIs.

Using the incidence of bacterial sexually transmitted infection (STI) as a surrogate for condomless sexual behavior, we assessed the association between STI and uncontrolled HIV replication among in-care persons with HIV (PWH) enrolled in a longitudinal HIV cohort study in the District of Columbia (the DC Cohort). Although STI occurrence initially correlated with higher HIV viral load (VL), this difference became more attenuated over time (2012-2016). This was true overall and among those with the greatest number of STIs [age 18-34, men who have sex with men (MSM)]. This likely reflects gains in population-wide virologic control through improved antiretroviral therapy and access to care, which helps mitigate the risk of HIV transmission.

Identifying Geographic Areas of Washington, DC, With Increased Potential for Sexual HIV Transmission Among People With HIV With STIs and Concurrent Elevated HIV RNA: Data From the DC Cohort.

Background: The Undetectable = Untransmittable (U = U) campaign advances the goal of ending the HIV epidemic by promoting durable viral suppression and therefore reducing sexual transmission. We used geospatial analysis to assess the potential for sexual HIV transmission by ZIP code of residence in the District of Columbia (DC) using data from the DC Cohort Longitudinal HIV Study (DC Cohort), a city-wide cohort of persons with HIV (PWH). Methods: DC Cohort participants aged ≥13 years were included in the study period between April 1, 2016, and March 31, 2018. Potential for sexual HIV transmission was defined as the proportion of participants with incident sexually transmitted infection (STI; gonorrhea, chlamydia, syphilis) and with HIV RNA ≥200 copies/mL from 9 months before to 3 months after STI diagnosis. We performed geographic information system (GIS) analysis to determine the ZIP codes with the highest potential for sexual HIV transmission. Results: Of 3467 participants, 367 (10.6%) had at least 1 incident STI, with 89.4% residing in 11 of the 20 residential ZIP codes in DC. Of the 367 participants with an incident STI, at least 1 HIV RNA was available for 348 (94.8%). Ninety-seven (27.9%) individuals with an incident STI had HIV RNA ≥200 copies/mL in the defined time window. Of these 97, 66 (68.0%) resided in 5 of the 20 DC ZIP codes. Conclusions: In DC, 5 ZIP codes of residence accounted for the majority of the estimated potential for HIV transmission among participants in the DC Cohort. These results support focused neighborhood-level interventions to help end the HIV epidemic.

Effect of FAmily CEntered (FACE®) Advance Care Planning on Longitudinal Congruence in End-of-Life Treatment Preferences: A Randomized Clinical Trial.

Trial tested effect of advance care planning on family/surrogates' understanding of patients' end-of-life treatment preferences longitudinally. A multisite, assessor-blinded, intent-to-treat, parallel-group, randomized controlled clinical trial in five hospital-based HIV clinics enrolled 449 participants aged 22 to 77 years during October 2013-March 2017. Patients living with HIV/family dyads were randomized at 2:1 ratio to 2 weekly ~ 60-min sessions either ACP (n = 155 dyads)-(1) ACP facilitated conversation, (2) Advance directive completion; or Control (n = 68 dyads)-(1) Developmental/relationship history, (2) Nutrition/exercise tips. ACP families/surrogates were more likely to accurately report patients' treatment preferences at Time 1 (T1) and 12 months post-intervention (T2) compared to controls, experiencing high congruence longitudinally (high→high transition), [63·6% vs 37·7% (difference = 25·9%, 95% CI: 11·3%, 40·4%, χ2 = 11·52, p = 0·01)], even as patients' preferences changed over time. ACP families/surrogates had eight times the odds of controls of having an excellent understanding of patients' treatment preferences (Adjusted Odds Ratio 7.91, 95%CI: 3.08, 20.3). Conversations matter.

Sexually transmitted infections in persons living with HIV infection and estimated HIV transmission risk: trends over time from the DC Cohort.

OBJECTIVE: A rise in incidence of STIs has been noted in the USA and in the District of Columbia (DC). We aim to describe changes in incident STIs among persons in care for HIV in Washington, DC as well as trends in HIV viral load among those with incident STIs. METHODS: We conducted a retrospective DC Cohort analysis (n=7810) measuring STI incidence (syphilis, gonorrhoea and chlamydia) as well as incare viral load (ICVL) and percentage with all viral loads less than the limit of detection (%

Quality of life of persons living with HIV and congruence with surrogate decision-makers.

PURPOSE: Physicians and caregivers rate patient quality of life (QOL) lower than patients rate their own QOL. This study investigated discrepancies between self-assessments of patient QOL by adults with HIV and their surrogate decision-makers. METHODS: We collected baseline data from 223 adult dyads in the FAmily-CEntered (FACE) Advance Care Planning (ACP) clinical trial, consisting of HIV positive patients and their chosen surrogates. Participants independently completed the Medical Outcome Study-HIV Survey (MOS-HIV) and the Palliative care Outcome Scale (POS). We used Wilcoxon Signed-Rank Test to assess differences in overall patient-surrogate means. We used Prevalence Adjusted Bias Adjusted Kappa (PABAK) statistics to assess dyadic agreement, with surrogate HIV status and cohabitation status as grouping variables. RESULTS: Patients were 56.1% male, 86.1% Black/African-American, aged 22-77 (mean = 50.83, SD = ± 12.33). Surrogates were 43.8% male, 84.1% Black/African-American, aged 18-82 (mean = 49.73, SD = ± 14.22). 46.2% of surrogates lived with the patient. 64.6% of surrogates reported negative HIV status. Surrogates were more likely to state patients were ill, p = 0.032. Among patient-surrogate dyads, most QOL assessments showed poor (0.00-0.39) or fair (0.40-0.59) agreement and agreement tended to be even poorer among patient-surrogate dyads where the surrogate had a shared HIV diagnosis. CONCLUSIONS: QOL discrepancies are said to arise from healthy surrogates overestimating the effects of chronic illness. In this novel assessment, many surrogates had a shared HIV diagnosis, without increased agreement. These findings highlight the challenge of accurately assessing patient QOL by surrogates, even when there is a shared HIV diagnosis. Improved communication is needed between patients and surrogates about the patients' representation of illness. National Clinical Trial Number: NCT01775436.

FAmily-CEntered (FACE) Advance Care Planning Among African-American and Non-African-American Adults Living With HIV in Washington, DC: A Randomized Controlled Trial to Increase Documentation and Health Equity.

CONTEXT: No prospective studies address disease-specific advance care planning (ACP) for adults living with HIV/AIDS. OBJECTIVE: To examine the efficacy of FAmily-CEntered (FACE) ACP in increasing ACP and advance directive documentation in the medical record. METHODS: Longitudinal, two-arm, randomized controlled trial with intent-to-treat design recruited from five hospital-based outpatient HIV clinics in Washington, DC. Adults living with HIV and their surrogate decision-makers (N = 233 dyads) were randomized to either an intensive facilitated two-session FACE ACP (Next Steps: Respecting Choices goals of care conversation and Five Wishes advance directive) or healthy living control (conversations about developmental/relationship history and nutrition). RESULTS: Patients (n = 223) mean age: 51 years, 56% male, 86% African-American. One hundred ninety-nine dyads participated in the intervention. At baseline, only 13% of patients had an advance directive. Three months after intervention, this increased to 59% for the FACE ACP group versus 17% in the control group (P < 0.0001). Controlling for race, the odds of having an advance directive in the medical record in the FACE ACP group was approximately seven times greater than controls (adjusted odds ratio = 6.58, 95% CI: 3.21-13.51, P < 0.0001). Among African-Americans randomized to FACE, 58% had completed/documented advance directives versus 20% of controls (P < 0.0001). CONCLUSIONS: The FACE ACP intervention significantly improved ACP completion and advance directive documentation in the medical record among both African-American and non-African-American adults living with HIV in Washington, DC, providing health equity in ACP, which can inform best practices.

Sexually Transmitted Infections Among HIV-Infected Individuals in the District of Columbia and Estimated HIV Transmission Risk: Data From the DC Cohort.

BACKGROUND: Washington, DC, has one of the highest rates of HIV infection in the United States. Sexual intercourse is the leading mode of HIV transmission, and sexually transmitted infections (STIs) are a risk factor for HIV acquisition and transmission. METHODS: We evaluated the incidence and demographic factors associated with chlamydia, gonorrhea, and syphilis among HIV-infected persons enrolled at 13 DC Cohort sites from 2011 to 2015. Using Poisson regression, we assessed covariates of risk for incident STIs. We also examined HIV viral loads (VLs) at the time of STI diagnosis as a proxy for HIV transmission risk. RESULTS: Six point seven percent (451/6672) developed an incident STI during a median follow-up of 32.5 months (4% chlamydia, 3% gonorrhea, 2% syphilis); 30% of participants had 2 or more STI episodes. The incidence rate of any STIs was 3.8 cases per 100 person-years (95% confidence interval [CI], 3.5-4.1); age 18-34 years, 10.8 (95% CI, 9.7-12.0); transgender women, 9.9 (95% CI, 6.9-14.0); Hispanics, 9.2 (95% CI, 7.2-11.8); and men who have sex with men (MSM), 7.7 (95% CI, 7.1-8.4). Multivariate Poisson regression showed younger age, Hispanic ethnicity, MSM risk, and higher nadir CD4 counts to be strongly associated with STIs. Among those with an STI, 41.8% had a detectable VL within 1 month of STI diagnosis, and 14.6% had a VL ≥1500 copies/mL. CONCLUSIONS: STIs are highly prevalent among HIV-infected persons receiving care in DC. HIV transmission risk is considerable at the time of STI diagnosis. Interventions toward risk reduction, antiretroviral therapy adherence, and HIV virologic suppression are critical at the time of STI evaluation.

Perceived discrimination and drug involvement among black primary care patients who use drugs.

Perceived discrimination has been associated with disparities for Black patients on a variety of health outcomes. Studies have suggested that perceived discrimination is associated with drug use in Blacks, but they have been limited by use of samples with little drug use and single measures of drug involvement. The current study examined the association between perceived discrimination and multiple measures of drug involvement among a sample of 203 Black adult primary care patients who were participants in a randomized trial of screening and brief intervention for drug use. The main independent variable was everyday perceived discrimination. The three outcomes were frequency of drug use in the past ninety days, drug-related consequences, and total drug involvement risk severity score from the Alcohol, Smoking, and Substance Involvement Test [ASSIST]. Analyses were conducted using negative binomial regression models for frequency and consequence outcomes and median regression models for drug involvement risk. Greater perceived discrimination was not significantly associated with frequency of use, but was associated with more drug-related consequences and a higher drug use risk level. These findings suggest that perceived discrimination may be an important variable to consider when selecting drug intervention approaches for Black primary care patients.

Perceived discrimination, racial identity, and health behaviors among black primary-care patients who use drugs.

Blacks who use drugs are at heightened risk for health problems. Discrimination experiences may contribute to these risks by influencing health behaviors. This study examined associations between discrimination, racial identity, and health behaviors (alcohol use, cigarette smoking, low physical activity, and unprotected [condomless] sex) in a sample of 203 Black primary-care patients who reported current drug use. Logistic regression analyses did not find direct effects of discrimination or identity on outcomes. Hypothesized moderation of discrimination by racial identity was not observed in expected direction for the outcome of unprotected sex.

HIV Nurse Navigation: Charting the Course to Improve Engagement in Care and HIV Virologic Suppression.

This study represents one of the few exploring the effectiveness of an integrated HIV nurse navigation program on engagement and virologic outcomes. A navigator provided individualized care management (eg, pillbox renewals), intensive outreach, and collaboration with existing support systems (eg, families, community programs). Clinical data from the Veterans Affairs (VA) Medical Center site of a longitudinal, observational study of HIV in the District of Columbia (DC) cohort were used for comparison (N = 706). Navigation patients (n = 84) were less likely to have permanent housing, and more likely to be disabled, have detectable viral load, comorbid depressive, and substance use disorders. Navigation patients showed improvements in clinic visits (doubled), rate of medication renewal (40.91% to 80.61%), CD4 count and CD4%, and viral rates of Veterans with <200 copies/mL increased from 47.6% to 69.0% after one year. Integration of nurse navigation into a HIV primary care setting shows promise in improving engagement and virologic suppression in a high-risk population.

True durability: HIV virologic suppression in an urban clinic and implications for timing of intensive adherence efforts and viral load monitoring.

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 % (95 % CI 32.2-41.6) in the first year, 26.9 % (95 % CI 21.7-32.1) in the year following one year of viral suppression, and 24.6 % (95 % CI 18.4-30.9) in the year following 2 years of viral suppression. However, for patients with CD4 ≥300 cells/µl who had 3-6 years of virologic suppression, the risk of viral rebound was very low. At the population level, the risk of viral rebound in a complex urban clinic population is surprisingly high even out to 3 years. Intensified monitoring and adherence efforts should target this high risk period. Thereafter, confidence in truly durable virologic suppression is improved.

Effects of alcohol cues and alcohol intoxication on drug use expectancies among men who have sex with men.

Although alcohol and drug use have been identified as HIV-risk factors for men who have sex with men (MSM), little is known about how they interact. An alcohol administration paradigm was used to examine alcohol's cue and pharmacological effects on perceived drug use benefits and consequences in 117 MSM. Planned contrasts indicated that those in the alcohol cue (i.e., placebo) condition reported lower perceived drug consequences compared to controls. No cue effects were found for drug benefits. There was no pharmacological effect of alcohol as compared to alcohol cue on either outcome. Findings suggest that alcohol cues may influence the perception of consequences related to drug use, which has implications for health interventions targeting substance use and HIV risk.

Energy expenditure of interruptions to sedentary behavior.

BACKGROUND: Advances in technology, social influences and environmental attributes have resulted in substantial portions of the day spent in sedentary pursuits. Sedentary behavior may be a cause of many chronic diseases including obesity, insulin resistance, type 2 diabetes and the metabolic syndrome. Research demonstrated that breaking up sedentary time was beneficially associated with markers of body composition, cardiovascular health and type 2 diabetes. Therefore, the purpose of this study was to quantify the total energy expenditure of three different durations of physical activity within a 30-minute sedentary period and to examine the potential benefits of interrupting sedentary behavior with physical activity for weight control. METHODS: Participants completed four consecutive 30-minute bouts of sedentary behavior (reading, working on the computer, or doing other desk activities) with and without interruptions of walking at a self-selected pace. Bout one contained no walking interruptions. Bout two contained a 1-minute walking period. Bout three contained a 2-minute walking period. Bout four contained a 5-minute walking period. Body composition and resting metabolic rate were assessed. RESULT: Twenty males and females (18-39 years) completed this study. Results of the repeated measures analysis of variance with post-hoc testing showed that significantly more energy was expended during each 30 minute sedentary bout with a walking break than in the 30 minute sedentary bout (p < 0.05 for all comparisons). On average, participants expended an additional 3.0, 7.4, and 16.5 additional net or activity kilocalories during bouts 2, 3, and 4, respectively compared with bout 1. When extrapolated for a full eight-hour working day, this data shows that an individual would theoretically expend an additional 24, 59 or 132 kilocalories per day, if they stood up and walked at a normal, self selected pace for one, two or five minutes every hour, respectively, compared with sitting for the 8-hour period. CONCLUSIONS: This study demonstrated that making small changes, such as taking a five minute walking break every hour could yield beneficial weight control or weight loss results. Therefore, taking breaks from sedentary time is a potential outlet to prevent obesity and the rise of obesity in developed countries.

Serotonin and its metabolism in basal deuterostomes: insights from Strongylocentrotus purpuratus and Xenoturbella bocki.

Serotonin (5-HT), an important molecule in metazoans, is involved in a range of biological processes including neurotransmission and neuromodulation. Both its creation and release are tightly regulated, as is its removal. Multiple neurochemical pathways are responsible for the catabolism of 5-HT and are phyla specific; therefore, by elucidating these catabolic pathways we glean greater understanding of the relationships and origins of various transmitter systems. Here, 5-HT catabolic pathways were studied in Strongylocentrotus purpuratus and Xenoturbella bocki, two organisms occupying distinct positions in deuterostomes. The 5-HT-related compounds detected in these organisms were compared with those reported in other phyla. In S. purpuratus, 5-HT-related metabolites include N-acetyl serotonin, gamma-glutamyl-serotonin and 5-hydroxyindole acetic acid; the quantity and type were found to vary based on the specific tissues analyzed. In addition to these compounds, varying levels of tryptamine were also seen. Upon addition of a 5-HT precursor and a monoamine oxidase inhibitor, 5-HT itself was detected. In similar experiments using X. bocki tissues, the 5-HT-related compounds found included 5-HT sulfate, gamma-glutamyl-serotonin and 5-hydroxyindole acetic acid, as well as 5-HT and tryptamine. The sea urchin metabolizes 5-HT in a manner similar to both gastropod mollusks, as evidenced by the detection of gamma-glutamyl-serotonin, and vertebrates, as indicated by the presence of 5-hydroxyindole acetic acid and N-acetyl serotonin. In contrast, 5-HT metabolism in X. bocki appears more similar to common protostome 5-HT catabolic pathways.

Serotonin catabolism in the central and enteric nervous systems of rats upon induction of serotonin syndrome.

Serotonin, a well-known neurotransmitter in mammals, has been linked to a number of neurological and gastrointestinal disorders. One of these disorders, serotonin syndrome, is a potentially deadly condition caused by increased levels of serotonin in the extracellular space. Information on the neurochemical effects of serotonin syndrome on serotonin catabolism is lacking, particularly in relation to the enteric system of the gastrointestinal tract. Here the catabolism of serotonin is monitored in rats with pharmacologically induced serotonin syndrome, with the catabolites characterized using a specialized capillary electrophoresis system with laser-induced native fluorescence detection. Animals induced with serotonin syndrome demonstrate striking increases in the levels of serotonin and its metabolites. In the brain, levels of serotonin increased 2- to 3-fold in animals induced with serotonin syndrome. A major serotonin metabolite, 5-hydroxyindole acetic acid, increased 10- to 100-fold in experimental animals. Similar results were observed in the gastrointestinal tissues; in the small intestines, serotonin levels increased 4- to 5-fold. Concentrations of 5-hydroxyindole acetic acid increased 32- to 100-fold in the intestinal tissues of experimental animals. Serotonin sulfate showed surprisingly large increases, marking what may be the first time the compound has been reported in rat intestinal tissues.

Serotonin catabolism and the formation and fate of 5-hydroxyindole thiazolidine carboxylic acid.

Serotonin (5-HT) functions as a neurotransmitter and neuromodulator in both the central and enteric nervous systems of mammals. The dynamic degradation of 5-HT metabolites in 5-HT-containing nervous system tissues is monitored by capillary electrophoresis with wavelength-resolved laser-induced native fluorescence detection in an effort to investigate known and novel 5-HT catabolic pathways. Tissue samples from wild type mice, genetically altered mice, Long Evans rats, and cultured differentiated rat pheochromocytoma PC-12 cells, are analyzed before and after incubation with excess 5-HT. From these experiments, several new compounds are detected. One metabolite, identified as 5-hydroxyindole thiazoladine carboxylic acid (5-HITCA), has been selected for further study. In 5-HT-incubated central and enteric nervous system tissue samples and differentiated PC-12 cells, 5-HITCA forms at levels equivalent to 5-hydroxyindole acetic acid, via a condensation reaction between L-cysteine and 5-hydroxyindole acetaldehyde. In the enteric nervous system, 5-HITCA is detected without the addition of 5-HT. The levels of L-cysteine and homocysteine in rat brain mitochondria are measured between 80 and 140 microm and 1.9 and 3.4 microm, respectively, demonstrating that 5-HITCA can be formed using available, free L-cysteine in these tissues. The lack of significant accumulation of 5-HITCA in the central and enteric nervous systems, along with data showing the degradation of 5-HITCA into 5-hydroxyindole acetaldehyde, suggests that an equilibrium coupled to the enzyme, aldehyde dehydrogenase type 2, prevents the accumulation of 5-HITCA. Even so, the formation of 5-HITCA represents a catabolic pathway of 5-HT that can affect the levels of 5-HT-derived compounds in the body.

Structural and spectroscopic studies of nickel(II) complexes with a library of Bis(oxime)amine-containing ligands.

A library of tripodal amine ligands with two oxime donor arms and a variable coordinating or noncoordinating third arm has been synthesized, including two chiral ligands based on l-phenylalanine. Their Ni(II) complexes have been synthesized and characterized by X-ray crystallography, UV-vis absorption, circular dichroism, and FTIR spectroscopy, mass spectrometry, and room-temperature magnetic susceptibility. At least one crystal structure is reported for all but one Ni/ligand combination. All show a six-coordinate pseudo-octahedral coordination geometry around the nickel center, with the bis(oxime)amine unit coordinating in a facial mode. Three distinct structure types are observed: (1) for tetradentate ligands, six-coordinate monomers are formed, with anions and/or solvent filling out the coordination sphere; (2) for tridentate ligands, six-coordinate monomers are formed with Ni(II)(NO(3))(2), with one monodentate and one bidentate nitrate filling the remaining coordination positions; (3) for tridentate ligands, six-coordinate, bis(mu-Cl) dimers are formed with Ni(II)Cl(2), with one terminal and two bridging chlorides filling the coordination sphere. The UV-vis absorption spectra of the complexes show that the value of 10 Dq varies according to the nature of the third arm of the ligand. The trend based on the third arm follows the order alkyl/aryl < amide < carboxylate < alcohol < pyridyl < oxime.