Integrating program-tailored universal trauma screening into HIV care: an evidence-based participatory approach.

Trauma is prevalent among HIV-infected populations and associated with negative HIV care outcomes. While several agencies have called for integrating trauma-informed care into HIV services, uptake has been limited and effective methods have not been delineated. To develop comprehensive trauma screening strategies tailored to a large, urban HIV care center, we aimed to first understand provider and staff perceptions of the center's current level of trauma screening and barriers and facilitators to universal screening uptake. We used a mixed-methods convergent parallel design: quantitative assessments with 31 providers and staff and in-depth interviews with 19 providers and staff. Quantitative assessments highlighted center strengths (i.e. assessing effects of trauma, explaining care plans to patients, providing opportunities for questions) and gaps (i.e. asking about head injuries, emotional safety). Qualitative interviews suggested center screening practices were highly-variable and limited, identified gaps in interdepartmental communication regarding results of trauma screening that led to repeated screenings and potential patient re-traumatization, screening barriers (i.e. limited time, competing clinical priorities) and facilitators (i.e. provider-driven, standardized, non-disruptive screening with clear cut-points and follow-up steps). This study provides tangible strategies for the center to begin integrating universal trauma screening, many of which could be adapted by other U.S. HIV clinics.

Marijuana Use and Its Associations With Pain, Opioid Dose, and HIV Viral Suppression Among Persons Living With HIV on Chronic Opioid Therapy.

BACKGROUND: Medical marijuana is legal in 29 US states and the District of Columbia: both HIV and chronic pain are "approved conditions" for receipt. Chronic pain is common among people living with HIV (PLWH). We anticipate PLWH will question their providers about medical marijuana for chronic pain. We examined marijuana use and its associations with pain, opioid dose, and HIV viral suppression among PLWH receiving chronic opioid therapy. METHODS: PLWH prescribed chronic opioid therapy were recruited into the Targeting Effective Analgesia in Clinics for HIV cohort. The main exposure variable was any past 12-month marijuana use. The primary outcomes were (1) opioid misuse (≥9 on the Current Opioid Misuse Measure) and (2) opioid dose (morphine equivalent daily dose). HIV viral load (VL) suppression (<200 copies/µL) and pain severity and interference using the Brief Pain Inventory were exploratory outcomes. RESULTS: Participants (n = 166) were men (65%), Black (72%), and had an undetectable VL (89%). We found no significant association between current marijuana use and opioid misuse, opioid dose, or pain. Current marijuana use was associated with 3.03 times the odds of having a detectable VL (95% odds ratio: 1.11-8.31, P = 0.03) while controlling for depressive symptoms and other substance use. DISCUSSION: We did not detect an association between marijuana use and opioid misuse behaviors, opioid dose, or pain. In an exploratory analysis, current marijuana use was associated with 3× greater odds of having a detectable VL. This study provides insights into potential consequences of marijuana use among PLWH with chronic pain.

The West coast regional safety pharmacology society meeting update: Filling translational gaps in safety assessment.

The Safety Pharmacology Society (SPS) held a West Coast Regional Meeting in Foster City, CA on November 14, 2018 at the Gilead Sciences Inc. site. The meeting was attended by scientists from the pharmaceutical and biotechnology industry, contract research organizations (CROs) and academia. A variety of scientific topics were presented by speakers, covering a broad variety of topics in the fields of safety risk assessment; from pro-arrhythmia and contractility risk evaluation, to models of heart failure and seizure in-a-dish; and discovery sciences; from stem cells and precision medicine, to models of inherited cardiomyopathy and precision cut tissue slices. The present review summarizes the highlights of the presentations and provides an overview of the high level of innovation currently underlying many frontiers in safety pharmacology.

Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia.

Human immunodeficiency virus (HIV) drug resistance is a major threat to the sustained impact of antiretroviral therapy (ART). We studied the epidemiology of drug resistance in the country of Georgia. The study included all adult patients who experienced virologic failure on first line ART and received HIV drug resistance testing between 2005 and 2016. The Stanford HIV Sequence Database was used for interpretation of the resistance data. Patient-level data were extracted from the national AIDS health information system. Of the 447 patients included, 85.5% harbored the subtype A6 virus, 8.0% - subtype B, 2.9% - subtype G, and other subtypes were <1%. The most frequent first-line regimens were Tenofovir/Emtricitabine/Efavirenz (28.4%), Zidovudine/Lamivudine/Efavirenz (28.4%), and Abacavir/Lamivudine/Efavirenz (15.9%). A total of 85.0% of the patients with treatment failure developed at least one drug resistance mutation affecting their susceptibility to ART. The most frequent nucleoside reverse transcriptase inhibitor mutations were M184V (65.3%), K65R (19.7%) and L74V (17.0%). At least three thymidine analogue mutations were detected in 6.3% of the patients. From non-nucleoside reverse transcriptase inhibitor mutations, G190S was shown to be the most prevalent (49.4%), followed by K101E (27.10%) and K103N (24.4%). G190S and K101E were more common in subtype A as compared with non-A viruses (G190S: 54.9% vs 11.3%, P < 0.0001; K101E: 29.8% vs 11.3%, P = 0.005). On the other hand, K103N was more frequent in non-A subtypes (43.4%) compared with subtype A (22.2%), P = 0.0008. A majority of persons failing on ART had HIV drug resistance. Drug resistance patterns may vary by subtype. K65R mutation remains below 20%, but given the high use of Tenofovir in the country, continuing surveillance of drug resistance is needed.

Brothers Building Brothers by Breaking Barriers: development of a resilience-building social capital intervention for young black gay and bisexual men living with HIV.

Young Black gay/bisexual and other men who have sex with men (YB-GBMSM) are disproportionately impacted by HIV/AIDS. Novel intervention strategies are needed to optimize engagement in HIV care for this population. We sought to develop a group-level intervention to enhance resilience by augmenting social capital (defined as the sum of resources in an individual's social network) among YB-GBMSM living with HIV, with the ultimate goal of improving engagement in HIV care. Our multiphase, community-based participatory research (CBPR) intervention development process included: (1) Development and maintenance of a youth advisory board (YAB) comprised of YB-GBMSM living with HIV; (2) Qualitative in-depth interviews with YB-GBMSM living with HIV; (3) Qualitative in-depth interviews with care and service providers at clinics and community-based organizations; and (4) Collaborative development of intervention modules and activities with our YAB, informed by social capital theory and our formative research results. The result of this process is Brothers Building Brothers By Breaking Barriers, a two-day, 10-module group-level intervention. The intervention does not focus exclusively on HIV, but rather takes a holistic approach to supporting youth and enhancing resilience. Intervention modules aim to develop resilience at the individual level (exploration of black gay identity, development of critical self-reflection and coping skills), social network level (exploring strategies for navigating family and intimate relationships) and community level (developing strategies for navigating clinical spaces and plans for community participation). Most intervention activities are interactive, in order to facilitate new social network connections - and accompanying social capital - within intervention groups. In summary, our intensive CBPR approach resulted in a novel, culturally-specific intervention designed to enhance HIV care engagement by augmenting resilience and social capital among YB-GBMSM living with HIV.

Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century.

Neisseria gonorrhoeae is a strictly human pathogen that is typically transmitted by sexual contact. The associated disease gonorrhea has plagued humankind for thousands of years, with a current estimated incidence of 78 million cases per year. Advances in antimicrobial discovery in the 1920s and 1930s leading to the discovery of sulfonamides and penicillin begun the era of effective antimicrobial treatment of gonorrhea. Unfortunately, the gonococcus developed decreased susceptibility or even resistance to these initially employed antibiotics, a trend that continued over subsequent decades with each new antibiotic that was brought into clinical practice. As this pattern of resistance has continued into the 21st century, there is now reason for great concern, especially in an era when few new antibiotics have prospects for use as treatment of gonorrhea. Here, we review the history of gonorrhea treatment regimens and gonococcal resistance to antibiotics, the mechanisms of resistance, resistance monitoring schemes that exist in different international settings, global responses to the challenge of resistance, and prospects for future treatment regimens in the 21st century.

CD4 Counts at Entry to HIV Care in Mexico for Patients under the "Universal Antiretroviral Treatment Program for the Uninsured Population," 2007-2014.

In Mexico, public health services have provided universal access to antiretroviral therapy (ART) since 2004. For individuals receiving HIV care in public healthcare facilities, the data are limited regarding CD4 T-lymphocyte counts (CD4e) at the time of entry into care. Relevant population-based estimates of CD4e are needed to inform strategies to maximize the impact of Mexico's national ART program, and may be applicable to other countries implementing universal HIV treatment programs. For this study, we retrospectively analyzed the CD4e of persons living with HIV and receiving care at state public health facilities from 2007 to 2014, comparing CD4e by demographic characteristics and the marginalization index of the state where treatment was provided, and assessing trends in CD4e over time. Our sample included 66,947 individuals who entered into HIV care between 2007 and 2014, of whom 79% were male. During the study period, the male-to-female ratio increased from 3.0 to 4.3, reflecting the country's HIV epidemic; the median age at entry decreased from 34 years to 32 years. Overall, 48.6% of individuals entered care with a CD4≤200 cells/µl, ranging from 42.2% in states with a very low marginalization index to 52.8% in states with a high marginalization index, and from 38.9% among individuals aged 18-29 to 56.5% among those older than 50. The adjusted geometric mean (95% confidence interval) CD4e increased among males from 135 (131,142) cells/µl in 2007 to 148 (143,155) cells/µl in 2014 (p-value<0.0001); no change was observed among women, with a geometric mean of 178 (171,186) and 171 (165,183) in 2007 and 2014, respectively. There have been important gains in access to HIV care and treatment; however, late entry into care remains an important barrier in achieving optimal outcomes of ART in Mexico. The geographic, socioeconomic, and demographic differences observed reflect important inequities in timely access to HIV prevention, care, and treatment services, and highlight the need to develop contextual and culturally appropriate prevention and HIV testing strategies and linkage programs.

High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial.

BACKGROUND: Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy. OBJECTIVE: We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease. DESIGN: The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative. RESULTS: Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/L). With vitamin D3, plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16. Adverse events and plasma calcium concentrations were similar between groups. In 192 subjects with culture-confirmed tuberculosis, an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [29 and 27 d, respectively; HR: 0.86; 95% CI: 0.63, 1.18; P = 0.33). Eight-week culture-conversion rates were also similar (84.0% and 82.1% for vitamin D3 and placebo, respectively; P = 0.99). CONCLUSION: A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086.

Addressing the challenges of the HIV continuum of care in high-prevalence cities in the United States.

In summary, addressing the challenges of the HIV care continuum is critical so that the goals of the NHAS can be achieved. CDC is working closely with federal partners, public health departments, and communities throughout the United States on multiple surveillance, programmatic, and research initiatives to inform and improve outcomes along the HIV care continuum. Currently, a large number of research projects are being conducted to describe the care continuum in various populations, assess and model the impact of interventions, and monitor the quality of care. To contribute to this knowledge base, NIH is working with its academic partners to support research that will inform the optimization of HIV treatment and prevention programs. As part of this focus, the CFAR/APC HIV Continuum of Care Working Group was formed to encourage communication between academic investigators and their local DOHs and to support joint research initiatives that are both timely and relevant to their own cities and environments. Finally, the results presented in this supplement may have implications for jurisdictions beyond those in which the studies were conducted.

Transition to adulthood and antiretroviral adherence among HIV-positive young Black men who have sex with men.

OBJECTIVES: We conducted a qualitative study of HIV-positive young Black men who have sex with men (YBMSM) to explore their experiences of living with HIV and adhering to antiretroviral medications (ARVs) within the developmental context of their transition to adulthood. METHODS: We conducted life history interviews with 20 HIV-positive YBMSM in Atlanta, Georgia, engaged in outpatient HIV care. We addressed these questions: (1) How do YBMSM living with HIV experience the transition to adulthood? and (2) What are the important sociocontextual influences on ARV adherence for YBMSM? RESULTS: Successful transition to adulthood and optimal ARV adherence were inextricably linked. HIV's detrimental impact on development was moderated by the degree of physical illness at diagnosis. Many participants described resilient trajectories while coping with HIV. Adherence problems occurred primarily among participants who were not meeting their developmental goals. CONCLUSIONS: Our findings support the need for early diagnosis and linkage to care, as well as the need to develop holistic, resilience-based interventions focusing on transition to adulthood. These findings have implications for individual clinical outcomes as well as ARV-based prevention efforts among YBMSM.

HIV and noncommunicable diseases (NCDs) in Latin America: a call for an integrated and comprehensive response.

The life expectancy of people living with HIV has dramatically improved with the much increased access to antiretroviral therapy. Consequently, a larger number of people living with HIV are living longer and facing the increased burden of noncommunicable diseases (NCDs). NCDs and HIV infection share common epidemiologic and sociodemographic characteristics that influence their outcomes, which may be difficult to address in the relatively weak health systems of the region. Data on the prevalence and interactions of NCDs and HIV in Latin American countries remain very limited, which hinders their governments' ability to make informed decisions about health care policies. Therefore, there is an urgent need to develop a research agenda that will be the basis for an integrated and comprehensive health care approach to HIV and NCD comorbidities in Latin America.

Spirituality, social capital and service: factors promoting resilience among Expert Patients living with HIV in Ethiopia.

People living with HIV (PLHIV) in Ethiopia and other developing nations face numerous challenges to their health and well-being, including poverty, limited healthcare infrastructure and high levels of societal stigma. Despite these challenges, resilient trajectories have been observed even within such resource-limited settings. In Ethiopia, such resilience is exemplified by the 'Expert Patients (EPTs)', HIV-positive lay health workers who function as adherence counsellors, health educators, outreach workers and community advocates. We conducted a multi-method qualitative study with 20 EPTs in Addis Ababa, Ethiopia in order to understand pathways to resilience in this selected population. Participants described three key mechanisms of resilient coping: (1) the use of spirituality and faith-based practices to manage psychological difficulties associated with living with HIV; (2) utilisation of social capital from family and community networks as a buffer against the psychological and economic consequences of societal stigma; and (3) serving others as a mechanism for finding optimism and purpose in life. Interventions designed to facilitate and/or augment these social processes in the wider community may be promising strategies for improving health among PLHIV in Ethiopia and other resource-limited settings.

Test of the usefulness of a paradigm to identify potential cardiovascular liabilities of four test articles with varying pharmacological properties in anesthetized guinea pigs.

The evaluation of proarrhythmic and hemodynamic liabilities for new compounds remains a major concern of preclinical safety assessment paradigms. Contrastingly, albeit functional liabilities can also translate to clinical morbidity and mortality, lesser preclinical efforts are focused on the evaluation of drug-induced changes in inotrope and lusitrope, particularly in the setting of concomitant hemodynamic/arrhythmic liabilities. This study aimed to establish the feasibility of an anesthetized guinea pig preparation to assess functional liabilities in the setting of simultaneous drug-induced electrocardiographic/hemodynamic changes, by evaluating the effects of various compounds with known cardiovascular properties on direct and indirect indices of left ventricular function. In short, twenty nine male guinea pigs were instrumented to measure electrocardiograms, systemic arterial pressure, and left ventricular pressure-volume relationships. After baseline measurement, all animals were given intravenous infusions of vehicle and two escalating concentrations of either chromanol 293B (n = 8), milrinone (n = 6), metoprolol (n = 7), or nicorandil (n = 8) for 10 minutes each. In all cases, these compounds produced the expected changes. The slope of preload-recruitable stroke work (PRSW), a pressure-volume derived load independent index, was the most sensitive marker of drug-induced changes in inotropy. Among the indirect functional indices studied, only the "contractility index" (dP/dtmax normalized by the pressure at its occurrence) and the static myocardial compliance (ratio of end diastolic volume and pressure) appeared to be adequate predictors of drug-induced changes in inotropy/lusitropy. Overall, the data confirms that both electrophysiological and mechanical liabilities can be accurately assessed in an anesthetized guinea pig preparation.

Neisseria gonorrhoeae antimicrobial resistance among men who have sex with men and men who have sex exclusively with women: the Gonococcal Isolate Surveillance Project, 2005-2010.

BACKGROUND: Gonorrhea treatment has been complicated by antimicrobial resistance in Neisseria gonorrhoeae. Gonococcal fluoroquinolone resistance emerged more rapidly among men who have sex with men (MSM) than men who have sex exclusively with women (MSW). OBJECTIVE: To determine whether N. gonorrhoeae urethral isolates from MSM were more likely than isolates from MSW to exhibit resistance to or elevated minimum inhibitory concentrations (MICs) of antimicrobials used to treat gonorrhea. DESIGN: 6 years of surveillance data from the Gonococcal Isolate Surveillance Project. SETTING: Publicly funded sexually transmitted disease clinics in 30 U.S. cities. PATIENTS: Men with a total of 34 600 episodes of symptomatic urethral gonorrhea. MEASUREMENTS: Percentage of isolates exhibiting resistance or elevated MICs and adjusted odds ratios for resistance or elevated MICs among isolates from MSM compared with isolates from MSW. RESULTS: In all U.S. regions except the West, isolates from MSM were significantly more likely to exhibit elevated MICs of ceftriaxone and azithromycin than isolates from MSW (P < 0.050). Isolates from MSM had a high prevalence of resistance to ciprofloxacin, penicillin, and tetracycline and were significantly more likely to exhibit antimicrobial resistance than isolates from MSW (P < 0.001). LIMITATIONS: Sentinel surveillance may not be representative of all patients with gonorrhea. HIV status, travel history, and antimicrobial use data were missing for some patients. CONCLUSION: Men who have sex with men are vulnerable to the emerging threat of antimicrobial-resistant N. gonorrhoeae. Because antimicrobial susceptibility testing is not routinely done in clinical practice, clinicians should monitor for treatment failures among MSM diagnosed with gonorrhea. Strengthened prevention strategies for MSM and new antimicrobial treatment options are needed.

Effectiveness of highly active antiretroviral therapy (HAART) among HIV-infected patients in Mexico.

The National Government HAART Program (NGP) for the provision of HAART to uninsured HIV-infected persons in Mexico began in 2001. The objective was to describe the virologic outcome of patients enrolled in the NGP in a large HIV treatment center in Mexico City. HIV-infected persons, naive or < or =6 months on HAART, who entered the NGP from 2001 to 2005 were included. Patients with virological suppression were compared to those with virologic failure (VF) during follow-up. Of 377 patients enrolled, 191 where eligible for analysis. The median age was 35.9 (18-75 years) and 85% were male. The median baseline CD4(+) T cell count was 183 cells/mm(3); 63.9% had <200 cells/mm(3) and/or an AIDS-defining event. During follow-up (median: 17.77 months), 55 patients (28.7%) changed their first regimen: 8.3% because of VF and the remaining due to toxicity. The probability of VF at 48 months was 20%. VF was associated with age <30 years (p = 0.003, RR 4.7, IC 95% 1.5-14.4). The use of NNRTI was associated with lower risk of VF (p = 0.042, RR 0.3, IC 95% 0.12-0.99). Nadir CD4(+) and AIDS-defining at baseline were not associated with VF. Implementation of NGP for HAART access in a specialized care setting in Mexico resulted in an excellent virologic response. Younger age was a significant risk factor for VF.

A new method to track seed dispersal and recruitment using 15N isotope enrichment.

Seed dispersal has a powerful influence on population dynamics, genetic structuring, evolutionary rates, and community ecology. Yet, patterns of seed dispersal are difficult to measure due to methodological shortcomings in tracking dispersed seeds from sources of interest. Here we introduce a new method to track seed dispersal: stable isotope enrichment. It consists of leaf-feeding plants with sprays of 15N-urea during the flowering stage such that seeds developed after applications are isotopically enriched. We conducted a greenhouse experiment with Solanum americanum and two field experiments with wild Capsicum annuum in southern Arizona, USA, to field-validate the method. First, we show that plants sprayed with 15N-urea reliably produce isotopically enriched progeny, and that delta 15N (i.e., the isotopic ratio) of seeds and seedlings is a linear function of the 15N-urea concentration sprayed on mothers. We demonstrate that three urea dosages can be used to distinctly enrich plants and unambiguously differentiate their offspring after seeds are dispersed by birds. We found that, with high urea dosages, the resulting delta 15N values in seedlings are 10(3) - 10(4) times higher than the delta 15N values of normal plants. This feature allows tracking not only where seeds arrive, but in locations where seeds germinate and recruit, because delta 15N enrichment is detectable in seedlings that have increased in mass by at least two orders of magnitude before fading to normal delta 15N values. Last, we tested a mixing model to analyze seed samples in bulk. We used the delta 15N values of batches (i.e., combined seedlings or seeds captured in seed traps) to estimate the number of enriched seeds coming from isotopically enriched plants in the field. We confirm that isotope enrichment, combined with batch-sampling, is a cheap, reliable, and user-friendly method for bulk-processing seeds and is thus excellent for the detection of rare dispersal events. This method could further the study of dispersal biology, including the elusive, but critically important, estimation of long-distance seed dispersal.

The cultural and community-level acceptance of antiretroviral therapy (ART) among traditional healers in Eastern Cape, South Africa.

The HIV/AIDS epidemic has profoundly impacted South Africa's healthcare system, greatly hampering its ability to scale-up the provision of antiretroviral therapy (ART). While one way to provide comprehensive care and prevention in sub-Saharan African countries has been through collaboration with traditional healers, long-term support specifically for ART has been low within this population. An exploratory, qualitative research project was conducted among 25 self-identified traditional healers between June and August of 2006 in the Lukhanji District of South Africa. By obtaining the opinions of traditional healers currently interested in biomedical approaches to HIV/AIDS care and prevention, this formative investigation identified a range of motivational factors that were believed to promote a deeper acceptance of and support for ART. These factors included cultural consistencies between traditional and biomedical medicine, education, as well as legal and financial incentives to collaborate. Through an incorporation of these factors into future HIV/AIDS treatment programs, South Africa and other sub-Saharan countries may dramatically strengthen their ability to provide ART in resource-poor settings.

The metabolic basis of whole-organism RNA and phosphorus content.

Understanding the storage, flux, and turnover of nutrients in organisms is important for quantifying contributions of biota to biogeochemical cycles. Here we present a model that predicts the storage of phosphorus-rich RNA and whole-body phosphorus content in eukaryotes based on the mass- and temperature-dependence of ATP production in mitochondria. Data from a broad assortment of eukaryotes support the model's two main predictions. First, whole-body RNA concentration is proportional to mitochondrial density and consequently scales with body mass to the -1/4 power. Second, whole-body phosphorus content declines with increasing body mass in eukaryotic unicells but approaches a relatively constant value in large multicellular animals because the fraction of phosphorus in RNA decreases relative to the fraction in other pools. Extension of the model shows that differences in the flux of RNA-associated phosphorus are due to the size dependencies of metabolic rate and RNA concentration. Thus, the model explicitly links two biological currencies at the individual level: energy in the form of ATP and materials in the form of phosphorus, both of which are critical to the functioning of ecosystems. The model provides a framework for linking attributes of individuals to the storage and flux of phosphorus in ecosystems.