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Background: Longitudinal studies of future overdose risk among people who inject drugs (PWID) are needed to inform planning of targeted overdose preventions in the United States. Methods: The Integrating Services to Improve Treatment and Engagement (INSITE) study followed 720 PWID between June 2018 and August 2019 to evaluate the delivery of mobilized healthcare services in Baltimore, Maryland. The present analyses used logistic regression to identify baseline characteristics predictive of non-fatal or fatal overdose during the 6-month follow-up among 507 participants with overdose information. Non-fatal overdoses were self-reported and fatal overdoses were identified through the National Death Index. Results: At baseline, 121 (23 %) reported an overdose in the prior 6 months. Between baseline and follow-up, 66 (13 %) participants reported a non-fatal overdose and 6 (1 %) experienced a fatal overdose. Overdose during follow-up was positively associated with overdose in the 6 months prior to baseline (6.70 aOR; 95 % CI: 3.51, 12.78) and more than 6 months prior to baseline (2.49 aOR; 95 % CI: 1.52, 4.08) versus no prior overdose. Overdose during follow-up was also positively associated with buprenorphine treatment (2.37 aOR; CI: 1.08, 5.21) and negatively associated with non-prescribed methadone at baseline (0.59 aOR; 0.38, 0.93). Conclusions: Identifying and intervening with PWID who experienced a recent overdose could reduce short-term elevated risk of future overdose. However, as other PWID reported never experiencing an overdose at baseline nonetheless experienced an overdose during follow-up, targeted approaches should be complemented with population-level interventions. Overdose risk implications of buprenorphine treatment and non-prescribed methadone are also discussed.

The increase in global population and industrial development has led to a significant release of organic and inorganic pollutants into water streams, threatening human health and ecosystems. Microalgae, encompassing eukaryotic protists and prokaryotic cyanobacteria, have emerged as a sustainable and cost-effective solution for removing these pollutants and mitigating carbon emissions. Various microalgae species, such as C. vulgaris, P. tricornutum, N. oceanica, A. platensis, and C. reinhardtii, have demonstrated their ability to eliminate heavy metals, salinity, plastics, and pesticides. Synthetic biology holds the potential to enhance microalgae-based technologies by broadening the scope of treatment targets and improving pollutant removal rates. This review provides an overview of the recent advances in the synthetic biology of microalgae, focusing on genetic engineering tools to facilitate the removal of inorganic (heavy metals and salinity) and organic (pesticides and plastics) compounds. The development of these tools is crucial for enhancing pollutant removal mechanisms through gene expression manipulation, DNA introduction into cells, and the generation of mutants with altered phenotypes. Additionally, the review discusses the principles of synthetic biology tools, emphasizing the significance of genetic engineering in targeting specific metabolic pathways and creating phenotypic changes. It also explores the use of precise engineering tools, such as CRISPR/Cas9 and TALENs, to adapt genetic engineering to various microalgae species. The review concludes that there is much potential for synthetic biology based approaches for pollutant removal using microalgae, but there is a need for expansion of the tools involved, including the development of universal cloning toolkits for the efficient and rapid assembly of mutants and transgenic expression strains, and the need for adaptation of genetic engineering tools to a wider range of microalgae species.

The AMP‐activated protein kinase (AMPK)‐related kinase NUAK1 (NUAK family SNF1‐like kinase 1) has emerged as a potential vulnerability in MYC‐dependent cancer but the biological roles of NUAK1 in different settings are poorly characterised, and the spectrum of cancer types that exhibit a requirement for NUAK1 is unknown. Unlike canonical oncogenes, NUAK1 is rarely mutated in cancer and appears to function as an obligate facilitator rather than a cancer driver per se. Although numerous groups have developed small‐molecule NUAK inhibitors, the circumstances that would trigger their use and the unwanted toxicities that may arise as a consequence of on‐target activity are thus undetermined. Reasoning that MYC is a key effector of RAS pathway signalling and the GTPase KRAS is almost uniformly mutated in pancreatic ductal adenocarcinoma (PDAC), we investigated whether this cancer type exhibits a functional requirement for NUAK1. Here, we show that high NUAK1 expression is associated with reduced overall survival in PDAC and that inhibition or depletion of NUAK1 suppresses growth of PDAC cells in culture. We identify a previously unknown role for NUAK1 in regulating accurate centrosome duplication and show that loss of NUAK1 triggers genomic instability. The latter activity is conserved in primary fibroblasts, raising the possibility of undesirable genotoxic effects of NUAK1 inhibition.

Abstract Introduction HIV controllers have low viral loads (VL) without antiretroviral treatment (ART). We evaluated viraemic control in a community‐randomized trial conducted in Zambia and South Africa that evaluated the impact of a combination prevention intervention on HIV incidence (HPTN 071 [PopART]; 2013–2018). Methods VL and antiretroviral (ARV) drug testing were performed using plasma samples collected 2 years after enrolment for 4072 participants who were HIV positive at the start of the study intervention. ARV drug use was assessed using a qualitative laboratory assay that detects 22 ARV drugs in five drug classes. Participants were classified as non‐controllers if they had a VL ≥2000 copies/ml with no ARV drugs detected at this visit. Additional VL and ARV drug testing was performed at a second annual study visit to confirm controller status. Participants were classified as controllers if they had VLs male, p = 0.027). There was no significant association between controller status and age, study country or herpes simplex virus type 2 (HSV‐2) status at study enrolment. Conclusions To our knowledge, this report presents the first large‐scale, population‐level study evaluating the prevalence of viraemic control and associated factors in Africa. A key advantage of this study was that a biomedical assessment was used to assess ARV drug use (vs. self‐reported data). This study identified a large cohort of HIV controllers and non‐controllers not taking ARV drugs, providing a unique repository of longitudinal samples for additional research. This cohort may be useful for further studies investigating the mechanisms of virologic control.

BackgroundHigh HIV viral load (VL) is associated with increased transmission risk and faster disease progression. HIV controllers achieve viral suppression without antiretroviral (ARV) treatment. We evaluated viremic control in a community-randomized trial with >48,000 participants.MethodsA massively multiplexed antibody profiling system, VirScan, was used to quantify pre- and post-infection antibody reactivity to HIV peptides in 664 samples from 429 participants (13 controllers, 135 viremic non-controllers, 64 other non-controllers, 217 uninfected persons). Controllers had VLs

ABSTRACT The objective of the study was to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the Howard County, Maryland, general population and demographic subpopulations attributable to natural infection or coronavirus disease 2019 (COVID-19) vaccination and to identify self-reported social behaviors that may affect the likelihood of recent or past SARS-CoV-2 infection. A cross-sectional, saliva-based serological study of 2,880 residents of Howard County, Maryland, was carried out from July through September 2021. Natural SARS-CoV-2 infection prevalence was estimated by inferring infections among individuals according to anti-nucleocapsid immunoglobin G levels and calculating averages weighted by sample proportions of various demographics. Antibody levels between BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) recipients were compared. Antibody decay rate was calculated by fitting exponential decay curves to cross-sectional indirect immunoassay data. Regression analysis was carried out to identify demographic factors, social behaviors, and attitudes that may be linked to an increased likelihood of natural infection. The estimated overall prevalence of natural infection in Howard County, Maryland, was 11.9% (95% confidence interval, 9.2% to 15.1%), compared with 7% reported COVID-19 cases. Antibody prevalence indicating natural infection was highest among Hispanic and non-Hispanic Black participants and lowest among non-Hispanic White and non-Hispanic Asian participants. Participants from census tracts with lower average household income also had higher natural infection rates. After accounting for multiple comparisons and correlations between participants, none of the behavior or attitude factors had significant effects on natural infection. At the same time, recipients of the mRNA-1273 vaccine had higher antibody levels than those of BNT162b2 vaccine recipients. Older study participants had overall lower antibody levels compared with younger study participants. The true prevalence of SARS-CoV-2 infection is higher than the number of reported COVID-19 cases in Howard County, Maryland. A disproportionate impact of infection-induced SARS-CoV-2 positivity was observed across different ethnic/racial subpopulations and incomes, and differences in antibody levels across different demographics were identified. Taken together, this information may inform public health policy to protect vulnerable populations. IMPORTANCE We employed a highly innovative noninvasive multiplex oral fluid SARS-CoV-2 IgG assay to ascertain our seroprevalence estimates. This laboratory-developed test has been applied in NCI’s SeroNet consortium, possesses high sensitivity and specificity according to FDA Emergency Use Authorization guidelines, correlates strongly with SARS-CoV-2 neutralizing antibody responses, and is Clinical Laboratory Improvement Amendments-approved by the Johns Hopkins Hospital Department of Pathology. It represents a broadly scalable public health tool to improve understanding of recent and past SARS-CoV-2 exposure and infection without drawing any blood. To our knowledge, this is the first application of a high-performance salivary SARS-CoV-2 IgG assay to estimate population-level seroprevalence, including identifying COVID-19 disparities. We also are the first to report differences in SARS-CoV-2 IgG responses by COVID-19 vaccine manufacturers (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]). Our findings demonstrate remarkable consistency with those of blood-based SARS-CoV-2 IgG assays in terms of differences in the magnitude of SARS-CoV-2 IgG responses between COVID-19 vaccines.

Objectives: HPTN 075 enrolled men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa. Persons in HIV care or on antiretroviral treatment (ART) were not eligible to enroll. We evaluated antiretroviral (ARV) drug use, viral suppression, and drug resistance in this cohort over a 12-month follow-up period. Methods: Assessments included 64 participants with HIV (39 MSM, 24 TGW, and one gender not specified). ARV drugs were detected using a qualitative assay. Viral load (VL) and drug resistance testing were performed using commercial assays. Results: Over 12 months, the proportion of participants using ARV drugs increased from 28.1% to 59.4% and the proportion with VLs

The NIH Rapid Acceleration of Diagnostics (RADxSM) Tech Program was created to speed the development, validation, and commercialization of innovative point-of-care (POC) and home-based tests, and to improve clinical laboratory tests, that can directly detect SARS-CoV-2. Leveraging the experience of the Point-of-Care Technologies Research Network, a Clinical Review Committee (CRC) composed of clinicians, bioengineers, regulatory experts, and laboratorians was created to provide structured feedback to SARS-CoV-2 diagnostic innovators. The CRC convened 53 meetings with 49 companies offering SARS-CoV-2 tests in POC and reference laboratory formats as well as collection materials. The CRC identified common barriers to device design finalization including biosafety, workflow, result reporting, regulatory requirements, sample type, supply chain, limit of detection, lack of relevant validation data, and price-performance-use mismatch. Feedback from companies participating was positive.

Anaerobic methanogenesis is dependent on key macronutrients (carbon, nitrogen and phosphorus) and trace metals (including iron, nickel and cobalt) to drive methane production. Reservoir derived methane emissions have correlated to eutrophication status, with elevated emissions associated with more eutrophic systems. Additionally, sediment organic matter can enhance methane emissions, particularly through the ebullition pathway. As such, it is critical to understand how organic carbon and nutrient inputs into reservoir water columns and sediments drive methanogenesis to improve flooded land greenhouse gas emission estimates. In this study we examine the methane potential of sediments in mesotrophic (Little Nerang Dam) and eutrophic (Lake Wivenhoe) sub-tropical reservoirs under different nutrient and organic carbon availabilities using biological methane potential (BMP) tests. BMP tests were conducted with sediments incubated under anaerobic conditions using replicate controls (reservoir bottom waters) or treatments (excess nutrient and/or organic carbon availability). The results indicated that these systems are carbon limited. The addition of organic carbon significantly increases anaerobic methanogenesis by 20-fold over controls. Analysis of sediment samples from the reservoirs showed that both reservoirs were replete in key macronutrient and trace metal content for methanogenesis. Finally, a comprehensive catchment monitoring program of Little Nerang Dam measuring catchment inflow events, lateral transport of forest litter, and bulk atmospheric deposition showed that catchment inflows and lateral transport of forest litter were strongly linked to rainfall and accounted for more than 99% of the total annual load. This suggests the frequency of rainfall events is a critical driver of organic matter inputs that drive reservoir methane emissions in the humid, sub-tropical region.

Pathologists who enter the workforce must have a diverse skill set beyond that of clinical diagnostics alone. Anticipating this need, the Johns Hopkins Pathology Residency Program developed Special Expertise Tracks to enhance training in relevant subspecialty domains. Using a combination of discussions and surveys, we assessed: (1) our current resident curriculum; (2) perceived curricular strengths and needs; (3) resident career preferences and ultimate career paths; (4) perceived barriers to implementing an advanced elective curriculum; and (5) available departmental/institutional resources. Additionally, we utilized the Accreditation Council for Graduate Medical Education Pathology Milestones as a curricular guide. Six professional residency training Special Expertise Tracks were established: Education, Physician-Scientist Research, Informatics, Quality Improvement/Quality Assurance/Value-Based Care, Health Policy/Hospital Management and Global Health. After implementation in 2017, the Education track has had 4 residents complete the curriculum successfully; the Physician-Scientist Research track has had 2 residents and the Informatics and Global Health tracks have each had one resident successfully complete their respective curricula. Currently, 5 residents are pursuing the Education track, one is pursuing the Physician-Scientist Research track, one is pursuing the Informatics track, and 2 residents are pursuing the Global Health track. Five residents have completed long-term projects including developing several e-learning modules, an online free digital cytopathology atlas, peer-reviewed articles, book chapters, and books. The Johns Hopkins Pathology Resident Special Expertise Track program provides pathology residents an opportunity to gain meaningful experience and additional skills tailored to their individual career interests.

Background: The Eastern Cape province of South Africa has one of the highest burdens of HIV in the world. Emergency Departments (EDs) can serve as optimal clinical sites for the identification of new HIV infections and entry into care. We sought to determine the current burden of HIV disease among ED patients in the Eastern Cape. Methods: We conducted a prospective cross-sectional observational study in the EDs of three Hospitals in the Eastern Cape province of South Africa from June 2017 to July 2018. All adult, non-critical patients presenting to the ED were systematically approached and offered a Point-Of-Care (POC) HIV test in accordance with South African guidelines. All HIV-positive individuals had their blood tested for the presence of antiretroviral therapy (ART) and the presence of viral suppression (≤1000 copies/ml). HIV incidence was estimated using a multi-assay algorithm, validated for a subtype C epidemic. Findings: Of the 2901 patients for whom HIV status was determined (either known HIV-positive or underwent POC HIV testing), 811 (28.0%) were HIV positive, of which 234 (28.9%) were newly diagnosed. HIV prevalence was higher in Mthatha [34% (388/1134) at Mthatha Regional Hospital and 28% (142/512) at Nelson Mandela Academic Hospital], compared to Port Elizabeth [22% (281/1255) at Livingstone Hospital]. HIV incidence was estimated at 4.5/100 person-years (95% CI: 2.4, 6.50) for women and 1.5 (CI 0.5, 2.5) for men. Of all HIV positive individuals tested for ART (585), 54% (316/585) tested positive for the presence of ARTs, and for all HIV positive participants with viral load data (609), 49% (299/609) were found to be virally suppressed. Interpretation: Our study not only observed a high prevalence and incidence of HIV among ED patients but also highlights significant attrition along the HIV care cascade for HIV positive individuals. Furthermore, despite developing an optimal testing environment, we were only able to enrol a small sub-set of the ED population. Given the high HIV prevalence and high attrition in the ED population, HIV services in the ED should also develop strategies that can accommodate large testing volumes and ART initiation. Keywords: HIV testing, HIV in men, South Africa, Emergency medicine, HIV and trauma

Purpose: To explore the utility of phosphorus magnetic resonance spectroscopy (31P MRS) in identifying anthracycline-induced cardiac toxicity in patients with breast cancer.Methods: Twenty patients with newly diagnosed breast cancer receiving anthracycline-based chemotherapy had cardiac magnetic resonance assessment of left ventricular ejection fraction (LVEF) and 31P MRS to determine myocardial Phosphocreatine/Adenosine Triphosphate Ratio (PCr/ATP) at three time points: pre-, mid-, and end-chemotherapy. Plasma high sensitivity cardiac troponin-I (cTn-I) tests and electrocardiograms were also performed at these same time points.Results: Phosphocreatine/Adenosine Triphosphate did not change significantly between pre- and mid-chemo (2.16 ± 0.46 vs. 2.00 ± 0.56, p = 0.80) and pre- and end-chemo (2.16 ± 0.46 vs. 2.17 ± 0.86, p = 0.99). Mean LVEF reduced significantly by 5.1% between pre- and end-chemo (61.4 ± 4.4 vs. 56.3 ± 8.1 %, p = 0.02). Change in PCr/ATP ratios from pre- to end-chemo correlated inversely with changes in LVEF over the same period (r = −0.65, p = 0.006). Plasma cTn-I increased progressively during chemotherapy from pre- to mid-chemo (1.35 ± 0.81 to 4.40 ± 2.64 ng/L; p = 0.01) and from mid- to end-chemo (4.40 ± 2.64 to 18.33 ± 13.23 ng/L; p = 0.001).Conclusions: In this small cohort pilot study, we did not observe a clear change in mean PCr/ATP values during chemotherapy despite evidence of increased plasma cardiac biomarkers and reduced LVEF. Future similar studies should be adequately powered to take account of patient drop-out and variable changes in PCr/ATP and could include T1 and T2 mapping.

BackgroundAssays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments.MethodsSamples were obtained from 220 seroconverters (infected 1 year) enrolled in an HIV prevention trial (HPTN 071 [PopART]); 28.6% of the seroconverters and 73.4% of the non-seroconverters had HIV viral loads ≤400 copies/mL. Samples were tested with two laboratory-based assays (LAg-Avidity, JHU BioRad-Avidity) and a point-of-care assay (rapid LAg). The four MAAs included different combinations of these assays and HIV viral load. Seroconverters on antiretroviral treatment (ART) were identified using a qualitative multi-drug assay.ResultsThe MAAs identified between 54 and 100 (25% to 46%) of the seroconverters as recently-infected. The false recent rate of the MAAs for infections >2 years duration ranged from 0.2%-1.3%. The MAAs classified different overlapping groups of individuals as recent vs. non-recent. Only 32 (15%) of the 220 seroconverters were classified as recent by all four MAAs. Viral suppression impacted the performance of the two LAg-based assays. LAg-Avidity assay values were also lower for seroconverters who were virally suppressed on ART compared to those with natural viral suppression.ConclusionsThe four MAAs evaluated varied in sensitivity and specificity for identifying persons infected

ObjectiveFemale sex workers (FSW) have increased risk of HIV infection. Antiretroviral treatment (ART) can improve HIV outcomes and prevent HIV transmission. We analyzed antiretroviral (ARV) drug use and HIV drug resistance among HIV-positive FSW in the Dominican Republic and Tanzania.MethodsPlasma samples collected at study entry with viral loads >1,000 copies/mL were tested for ARV drugs and HIV drug resistance. ARV drug testing was performed using a qualitative assay that detects 22 ARV drugs in five classes. HIV genotyping was performed using the ViroSeq HIV-1 Genotyping System. Phylogenetic analyses were performed to determine HIV subtype and assess transmission clusters.ResultsAmong 410 FSW, 144 (35.1%) had viral loads >1,000 copies/mL (DR: n = 50; Tanzania: n = 94). ARV drugs were detected in 36 (25.0%) of 144 samples. HIV genotyping results were obtained for 138 (95.8%) cases. No transmission clusters were observed in either country. HIV drug resistance was detected in 54 (39.1%) of 138 samples (31/35 [88.6%] with drugs detected; 23/103 [22.3%] without drugs detected); 29/138 (21.0%) had multi-class resistance (MCR). None with MCR had integrase strand transfer inhibitor resistance. In eight cases, one or more ARV drug was detected without corresponding resistance mutations; those women were at risk of acquiring additional drug resistance. Using multivariate logistic regression, resistance was associated with ARV drug detection (pConclusionsIn this cohort, many women were on ART, but were not virally suppressed. High levels of HIV drug resistance, including MCR, were observed. Resistance was associated with detection of ARV drugs, self-report of ART with full or partial adherence, and duration of HIV infection. These findings highlight the need for better HIV care among FSW to improve their health, reduce HIV drug resistance, and decrease risk of transmission to others.

BackgroundPersons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment.MethodsHPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment.ResultsFifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm.ConclusionsIn HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART.

Background: Outpatient cardiac rehabilitation (OP-CR) is a highly beneficial program but vastly under utilized. Methods: The efficacy of a text-messaging program was analyzed to determine if implementation could improve number of OP-CR sessions completed. All patients enrolled in OP-CR from July 2011 through December 2012 were invited to join a text-messaging program on their first visit. The program required that the patient possesses a cell phone with texting capabilities. Participants received three to five text-messages per week offering heart-healthy tips and requests for body weight, minutes of exercise, blood pressure, and medication adherence. Patients enrolled (n = 52) in the texting program (Tx) were compared with those who were not (n = 185) (NTx) in several clinical indices and were compared using matched pairs (same subjects), comparison of means and frequencies, chi-square statistics, t-tests, and the Wilcoxon Rank Sum test. Results: Significantly more patients in the Tx group completed the OP-CR program (61.5% versus 50%, p = 0.01). For those completing OP-CR, subjects in the Tx group completed significantly more sessions (31.4) than the NTx group (25.3) (p = 0.01). Additionally, significantly more in the Tx group were younger than those in the Ntx group. Conclusions: Patients enrolled in OP-CR who participated in a text-messaging program were younger, attended significantly more sessions and were significantly more likely to complete the program.

BACKGROUND:HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. METHODS:A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits. RESULTS:Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment. CONCLUSIONS:HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.

Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1-4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals.

(131)I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of (131)I-CLR1404.Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131)I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on (127)I-CLR1404 mass measurements. To evaluate renal clearance of (131)I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.Single administrations of 370 MBq of (131)I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127)I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.Preliminary data suggest that (131)I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.ClinicalTrials.gov NCT00925275.

American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood.Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with HIV compared to being HIV-uninfected or previously diagnosed with HIV.HPTN 061 enrolled 1553 Black MSM whose median age was 40; 30% self-identified exclusively as gay or homosexual, 29% exclusively as bisexual, and 3% as transgender. About 1/6(th) (16.2%) were previously diagnosed with HIV (PD); of 1263 participants without a prior HIV diagnosis 7.6% were newly diagnosed (ND). Compared to PD, ND Black MSM were younger (p

BackgroundNational Institute of Mental Health Project Accept (HIV Prevention Trials Network [HPTN] 043) is a large, Phase III, community-randomized, HIV prevention trial conducted in 48 matched communities in Africa and Thailand. The study intervention included enhanced community-based voluntary counseling and testing. The primary endpoint was HIV incidence, assessed in a single, cross-sectional, post-intervention survey of >50,000 participants.MethodsHIV rapid tests were performed in-country. HIV status was confirmed at a central laboratory in the United States. HIV incidence was estimated using a multi-assay algorithm (MAA) that included the BED capture immunoassay, an avidity assay, CD4 cell count, and HIV viral load.ResultsData from Thailand was not used in the endpoint analysis because HIV prevalence was low. Overall, 7,361 HIV infections were identified (4 acute, 3 early, and 7,354 established infections). Samples from established infections were analyzed using the MAA; 467 MAA positive samples were identified; 29 of those samples were excluded because they contained antiretroviral drugs. HIV prevalence was 16.5% (range at study sites: 5.93% to 30.8%). HIV incidence was 1.60% (range at study sites: 0.78% to 3.90%).ConclusionsIn this community-randomized trial, a MAA was used to estimate HIV incidence in a single, cross-sectional post-intervention survey. Results from this analysis were subsequently used to compare HIV incidence in the control and intervention communities.Trial registrationClinicalTrials.gov NCT00203749.