OBJECTIVES: To propose a framework for adoption of privacy-preserving record linkage (PPRL) for public health applications. METHODS: Twelve interviews with subject matter experts (SMEs) were conducted virtually and coded using an inductive approach. A collaborative session was conducted with SMEs to identify key steps in the PPRL project lifecycle which informed development of a PPRL implementation checklist. RESULTS: This framework has 2 decision-making levels: the organization level and the project or program level. Organization-level considerations include PPRL governance, the optimal choice among approved PPRL solutions, the need for longitudinal linkages, the potential issue of vendor lock-in, and costs. Program-level considerations include characteristics of the PPRL use case, linkage quality and accuracy, data privacy and use, security thresholds, compatibility with data owners' data architecture, and trade-offs between open-source and commercial PPRL solutions. A PPRL implementation checklist was developed to guide public health practitioners considering PPRL for data linkage. CONCLUSIONS: The framework may be considered by public health entities to guide adoption and implementation of PPRL in public health research and surveillance. Public health experts may refer to this framework and the PPRL implementation checklist when determining the appropriateness of PPRL for specific use cases and implementation planning.

Nano-sized titanium dioxide particles (TiO(2) NPs) are a high-production volume nanomaterial widely used in the paints, cosmetics, food and photovoltaics industry. However, the potential carcinogenic effects of TiO(2) NPs in the lung are still unclear despite the vast number of in vitro and in vivo studies investigating TiO(2) NPs. Here, we systematically reviewed the existing in vitro and in vivo mechanistic evidence of TiO(2) NP lung carcinogenicity using the ten key characteristics of carcinogens for identifying and classifying carcinogens. A total of 346 studies qualified for the quality and reliability assessment, of which 206 were considered good quality. Using a weight-of-evidence approach, these studies provided mainly moderate to high confidence for the biological endpoints regarding genotoxicity, oxidative stress and chronic inflammation. A limited number of studies investigated other endpoints important to carcinogenesis, relating to proliferation and transformation, epigenetic alterations and receptor-mediated effects. In summary, TiO(2) NPs might possess the ability to induce chronic inflammation and oxidative stress, but it was challenging to compare the findings in the studies due to the wide variety of TiO(2) NPs differing in their physicochemical characteristics, formulation, exposure scenarios/test systems, and experimental protocols. Given the limited number of high-quality and high-reliability studies identified within this review, there is a lack of good enough mechanistic evidence for TiO(2) NP lung carcinogenicity. Future toxicology/carcinogenicity research must consider including positive controls, endotoxin testing (where necessary), statistical power analysis, and relevant biological endpoints, to improve the study quality and provide reliable data for evaluating TiO(2) NP-induced lung carcinogenicity.

OBJECTIVES: To understand the landscape of privacy preserving record linkage (PPRL) applications in public health, assess estimates of PPRL accuracy and privacy, and evaluate factors for PPRL adoption. MATERIALS AND METHODS: A literature scan examined the accuracy, data privacy, and scalability of PPRL in public health. Twelve interviews with subject matter experts were conducted and coded using an inductive approach to identify factors related to PPRL adoption. RESULTS: PPRL has a high level of linkage quality and accuracy. PPRL linkage quality was comparable to that of clear text linkage methods (requiring direct personally identifiable information [PII]) for linkage across various settings and research questions. Accuracy of PPRL depended on several components, such as PPRL technique, and the proportion of missingness and errors in underlying data. Strategies to increase adoption include increasing understanding of PPRL, improving data owner buy-in, establishing governance structure and oversight, and developing a public health implementation strategy for PPRL. DISCUSSION: PPRL protects privacy by eliminating the need to share PII for linkage, but the accuracy and linkage quality depend on factors including the choice of PPRL technique and specific PII used to create encrypted identifiers. Large-scale implementations of PPRL linking millions of observations-including PCORnet, National Institutes for Health N3C, and the Centers for Disease Control and Prevention COVID-19 project have demonstrated the scalability of PPRL for public health applications. CONCLUSIONS: Applications of PPRL in public health have demonstrated their value for the public health community. Although gaps must be addressed before wide implementation, PPRL is a promising solution to data linkage challenges faced by the public health ecosystem.

Astrocytes are an abundantly distributed population of glial cells in the central nervous system (CNS) that perform myriad functions in the normal and injured/diseased brain. Astrocytes exhibit heterogeneous phenotypes in response to various insults, a process known as astrocyte reactivity. The accuracy and precision of brain signaling are primarily based on interactions involving neurons, astrocytes, oligodendrocytes, microglia, pericytes, and dendritic cells within the CNS. Astrocytes have emerged as a critical entity within the brain because of their unique role in recycling neurotransmitters, actively modulating the ionic environment, regulating cholesterol and sphingolipid metabolism, and influencing cellular crosstalk in diverse neural injury conditions and neurodegenerative disorders. However, little is known about how an astrocyte functions in synapse formation, axon specification, neuroplasticity, neural homeostasis, neural network activity following dynamic surveillance, and CNS structure in neurological diseases. Interestingly, the tripartite synapse hypothesis came to light to fill some knowledge gaps that constitute an interaction of a subpopulation of astrocytes, neurons, and synapses. This review highlights astrocytes' role in health and neurological/neurodegenerative diseases arising from the omnidirectional signaling between astrocytes and neurons at the tripartite synapse. The review also recapitulates the disruption of the tripartite synapse with a focus on perturbations of the homeostatic astrocytic function as a key driver to modulate the molecular and physiological processes toward neurodegenerative diseases.

Occupational injuries and toxicant exposures lead to the development of neuroinflammation by activating distinct mechanistic signaling cascades that ultimately culminate in the disruption of neuronal function leading to neurological and neurodegenerative disorders. The entry of toxicants into the brain causes the subsequent activation of glial cells, a response known as 'reactive gliosis'. Reactive glial cells secrete a wide variety of signaling molecules in response to neuronal perturbations and thus play a crucial role in the progression and regulation of central nervous system (CNS) injury. In parallel, the roles of protein phosphorylation and cell signaling in eliciting neuroinflammation are evolving. However, there is limited understanding of the molecular underpinnings associated with toxicant- or occupational injury-mediated neuroinflammation, gliosis, and neurological outcomes. The activation of signaling molecules has biological significance, including the promotion or inhibition of disease mechanisms. Nevertheless, the regulatory mechanisms of synergism or antagonism among intracellular signaling pathways remain elusive. This review highlights the research focusing on the direct interaction between the immune system and the toxicant- or occupational injury-induced gliosis. Specifically, the role of occupational injuries, e.g., trips, slips, and falls resulting in traumatic brain injury, and occupational toxicants, e.g., volatile organic compounds, metals, and nanoparticles/nanomaterials in the development of neuroinflammation and neurological or neurodegenerative diseases are highlighted. Further, this review recapitulates the recent advancement related to the characterization of the molecular mechanisms comprising protein phosphorylation and cell signaling, culminating in neuroinflammation.

Well-characterized HPV serology assays are required to evaluate performance of biosimilar candidate vaccines, reduced dosing schedules and novel administration methods. We report characterization of an expanded assay, M9ELISA, that detects antibodies to HPV virus-like particles (VLP) of nine types using direct IgG ELISA on the Meso Scale Discovery (MSD) electrochemiluminescence platform. The method is based on the previously published M4ELISA which detects antibodies to HPV6,11,16, and 18. It has been modified to add detection of antibodies to HPV31,33,45,52 and 58, and to streamline assay and reduce background. The M9ELISA plates were prepared with purified type specific L1 + L2 VLPs coated on 10-spot/well standard MSD microplates. Results of ELISA on three serial dilutions of serum were read on MSD imager, and titers calculated using the parallel line method. Evaluations included dynamic range, assay reproducibility, and stability over time. We compared M9ELISA results to those from a pseudovirion-based neutralization assay in sera from a mixed cohort of unvaccinated and vaccinated individuals (n = ~116) and to competitive Luminex immunoassay (cLIA) results in sera from a predominantly unvaccinated cohort (n = 4426). The linear range of the assay extended over 5 logs, with inter-assay reproducibility coefficient of variation ≤25% for all types. The pre-coated plates were stable for at least 2 years. Spearman correlation of antibody titers showed excellent correlation with PBNA (r = 0.86-0.97) and moderate correlation (r = 0.52-0.68) with cLIA. Thus, the M9ELISA can serve as a useful platform for high-throughput, sensitive and simultaneous quantitation of the antibody responses to nine HPV vaccine types.

BACKGROUND: Resource-limited countries in Africa experience blood shortages. Understanding clinical drivers of blood demand can inform strategies to increase blood availability. STUDY DESIGN AND METHODS: From a national representative sample of 42 hospitals in Tanzania, patient records and requests for whole blood (WB) and red blood cells (RBCs) to treat anemia were analyzed using data collected prospectively from June through September 2013. Abstracted data included cause of anemia, number of requested units, clinical signs, and pretransfusion hemoglobin (Hb) levels. Weighted projections of nationwide drivers of blood demand for the year, 2013, were calculated. Mean posttransfusion Hb levels were estimated, and blood requests were assessed for clinical appropriateness. RESULTS: Malaria was the leading driver of blood demand for anemia among children, accounting for 67% (55,949 units; standard deviation [SD], 1911 units) of projected units requested for children in 2013. Maternal hemorrhage was the leading driver of blood demand for anemia among adults, accounting for 21% (31,321 units; SD, 963 units) of projected units requested. Seventeen percent (26,133 units; SD, 1013 units) of projected requested units were deemed inappropriate. Adults with severe anemia had a mean Hb level of 3.7 g/dL and a mean of 1.6 WB or RBC units per request, resulting in an estimated mean posttransfusion Hb level of 5.3 g/dL. CONCLUSIONS: Strategies to prevent and treat underlying causes of anemia and decrease inappropriate blood requests will likely increase blood availability. Restrictive blood ordering practices seen in adults with severe anemia suggests undertreatment of anemia and may result in an underestimation of the national blood demand.

Estimating blood demand to determine collection goals challenges many low-income countries. We sampled Tanzanian hospitals to estimate national blood demand. A representative sample based on probability proportional to size sampling of 42 of 273 (15%) Tanzanian transfusing hospitals was selected. Blood bank registers, patient medical records, and blood component disposition records were reviewed prospectively from June to September 2013 to determine the number of components requested and the number and proportion issued, not issued due to nonavailability, and not issued for other reasons. Data were estimated for an annual national estimate. Of an estimated 278 371 components requested in 2013, 6648 (2.4%) were not issued due to nonavailability, 34 591 (12.4%) were not issued for other reasons, and 244 535 (87.8%) were issued. Of these 278 371 components, 86 753 (31.2%) were requested by adult medical, 74 499 (26.8%) by pediatric medical, and 57 312 (20.6%) by obstetric units. In these 3 units, the proportion of units not issued due to nonavailability was 1.8%. Private (4.1%) and large (6%) hospitals had the largest proportion of units not issued because of nonavailability. Of 244 535 issued components, 91 690 (37.5%) were collected, tested, and issued from blood banks that are not part of the Tanzania National Blood Transfusion Services (TNBTS). Nearly 98% of blood component demand was met. However, a large portion of the blood supply for the hospitals came from non-TNBTS blood banks. TNBTS could increase availability of safe blood through assuring the quality of donor selection and donation testing at non-TNBTS blood banks.

INTRODUCTION: Seven district-level Nutritional Rehabilitation Centres (NRCs) in Bihar, India provide clinical and nutritional care for children with severe acute malnutrition (SAM). AIM: To assess whether intensified case finding (ICF) strategies at NRCs can lead to pediatric case detection among SAM children and link them to TB treatment under the Revised National Tuberculosis Control Programme (RNTCP). MATERIALS AND METHODS: A retrospective cohort study was conducted that included medical record reviews of SAM children registered for TB screening and RNTCP care during July-December 2012. RESULTS: Among 440 SAM children screened, 39 (8.8%) were diagnosed with TB. Among these, 34 (87%) initiated TB treatment and 18 (53%) were registered with the RNTCP. Of 16 children not registered under the RNTCP, nine (56%) weighed below six kilograms-the current weight requirement for receiving drugs under RNTCP. CONCLUSION: ICF approaches are feasible at NRCs; however, screening for TB entails diagnostic challenges, especially among SAM children. However, only half of the children diagnosed with TB were treated by the RNTCP. More effort is needed to link this vulnerable population to TB services in addition to introducing child-friendly drug formulations for covering children weighing less than six kilograms.

BACKGROUND: Examining small-area differences in the strength of declining heart disease mortality by race and sex provides important context for current racial and geographic disparities and identifies localities that could benefit from targeted interventions. We identified and described temporal trends in declining county-level heart disease mortality by race, sex, and geography between 1973 and 2010. METHODS AND RESULTS: Using a Bayesian hierarchical model, we estimated age-adjusted mortality with diseases of the heart listed as the underlying cause for 3099 counties. County-level percentage declines were calculated by race and sex for 3 time periods (1973-1985, 1986-1997, 1998-2010). Strong declines were statistically faster or no different than the total national decline in that time period. We observed county-level race-sex disparities in heart disease mortality trends. Continual (from 1973 to 2010) strong declines occurred in 73.2%, 44.6%, 15.5%, and 17.3% of counties for white men, white women, black men, and black women, respectively. Delayed (1998-2010) strong declines occurred in 15.4%, 42.0%, 75.5%, and 76.6% of counties for white men, white women, black men, and black women, respectively. Counties with the weakest patterns of decline were concentrated in the South. CONCLUSIONS: Since 1973, heart disease mortality has declined substantially for these race-sex groups. Patterns of decline differed by race and geography, reflecting potential disparities in national and local drivers of these declines. Better understanding of racial and geographic disparities in the diffusion of heart disease prevention and treatment may allow us to find clues to progress toward racial and geographic equity in heart disease mortality.

BACKGROUND: Namibia's HIV prevalence is 13.3 %. Alcohol is associated with sexual risk-taking, leading to increased HIV risk. Baseline sexual behaviors, HIV and alcohol knowledge, and self-perceived HIV risk were examined among men reporting high-risk drinking in Katutura, Namibia. METHODS: HIV negative men, ≥ 18 years, were screened for harmful or hazardous levels of drinking and >1 recent sex partner prior to randomization into control or intervention arm. SAS 9.3 and R 3.01 were used for descriptive baseline cohort analyses. RESULTS: A total of 501 participants who met criteria were included in analysis (mean Alcohol Use Disorders Identification Test [AUDIT] =12.4). HIV and alcohol knowledge were high with the majority (>85 and 89.8-98 %, respectively) of respondents correctly answering assessment questions. Despite high knowledge levels, 66.7 % of men felt they were at some or high risk of HIV acquisition. Among those respondents, 56.5 % stated often wanting to have sex after drinking and 40.3 % stated sex was better when drunk. Among respondents with non-steady partners [n = 188], 44.1 % of last sexual encounters occurred while the participant was drunk and condoms were not used 32.5 % of those times. Among persons who were not drunk condoms were not used 13.3 % of those times. CONCLUSIONS: Sex with casual partners was high. Inconsistent condom use and alcohol use before sex were frequently reported. Increased emphasis on alcohol risk-reduction strategies, including drinking due to peer pressure and unsafe sexual behaviors, is needed.

An observational cohort analysis was conducted within the Surveillance, Prevention, and Management of Diabetes Mellitus (SUPREME-DM) DataLink, a consortium of 11 integrated health-care delivery systems with electronic health records in 10 US states. Among nearly 7 million adults aged 20 years or older, we estimated annual diabetes incidence per 1,000 persons overall and by age, sex, race/ethnicity, and body mass index. We identified 289,050 incident cases of diabetes. Age- and sex-adjusted population incidence was stable between 2006 and 2010, ranging from 10.3 per 1,000 adults (95% confidence interval (CI): 9.8, 10.7) to 11.3 per 1,000 adults (95% CI: 11.0, 11.7). Adjusted incidence was significantly higher in 2011 (11.5, 95% CI: 10.9, 12.0) than in the 2 years with the lowest incidence. A similar pattern was observed in most prespecified subgroups, but only the differences for persons who were not white were significant. In 2006, 56% of incident cases had a glycated hemoglobin (hemoglobin A1c) test as one of the pair of events identifying diabetes. By 2011, that number was 74%. In conclusion, overall diabetes incidence in this population did not significantly increase between 2006 and 2010, but increases in hemoglobin A1c testing may have contributed to rising diabetes incidence among nonwhites in 2011.

OBJECTIVES: We hypothesised that among nursing home decedents, nursing home for-profit status and poor quality-of-care ratings, as well as patient characteristics, would lower the likelihood of transfer to hospital prior to heart disease death. METHODS: Using death certificates from a large metropolitan area (Tampa Florida Metropolitan Statistical Area) for 1998-2002, we geocoded residential street addresses of heart disease decedents to identify 2172 persons who resided in nursing homes (n=131) at the time of death. We analysed decedent place of death as an indicator of transfer prior to death. Multilevel logistic regression modelling was used for analysis. Cause of death and decedent characteristics were obtained from death certificates. Nursing home characteristics, including state inspector ratings for multiple time points, were obtained from Florida's Agency for Healthcare Administration. RESULTS: Nursing home for-profit status, level of nursing care and quality-of-care ratings were not associated with the likelihood of transfer to hospital prior to heart disease death. Nursing homes >5 miles from a hospital were more likely to transfer decedents, compared with facilities located close to a hospital. Significant predictors of no transfer for nursing home residents were being white, female, older, less educated and widowed/unmarried. CONCLUSIONS: In this study population, contrary to our hypotheses, sociodemographic characteristics of nursing home decedents were more important predictors of no transfer prior to cardiac death than quality rankings or for-profit status of nursing homes.

This article describes the frequency of alcohol use among HIV-positive patients attending clinical care in sub-Saharan Africa and explores the association between alcohol use, medication adherence, and sexual risk behavior. Data from 3538 patients attending an HIV clinic in Kenya, Tanzania, or Namibia were captured through interview and medical record abstraction. Participants were categorized into three drinking categories: nondrinkers, nonharmful drinkers, and harmful/likely dependent drinkers. A proportional odds model was used to identify correlates associated with categories of alcohol use. Overall, 20% of participants reported alcohol use in the past 6 months; 15% were categorized as nonharmful drinkers and 5% as harmful/likely dependent drinkers. Participants who reported missing a dose of their HIV medications [adjusted odds ratio (AOR): 2.04, 95% confidence interval (CI): 1.67, 2.49]; inconsistent condom use (AOR: 1.49, 95% CI: 1.23, 1.79); exchanging sex for food, money, gifts, or a place to stay (AOR: 1.57, 95% CI: 1.06, 2.32); and having a sexually transmitted infection symptom (AOR: 1.40, 95% CI: 1.10, 1.77) were more likely to be categorized in the higher risk drinking categories. This research highlights the need to integrate alcohol screening and counseling into the adherence and risk reduction counseling offered to HIV-positive patients as part of their routine care. Moreover, given the numerous intersections between alcohol and HIV, policies that focus on reducing alcohol consumption and alcohol-related risk behavior should be integrated into HIV prevention, care, and treatment strategies.

In sub-Saharan Africa, only South Africa has had a long-standing national haemovigilance system to monitor acute transfusion reactions (ATR) (Nel and Heyns, 2000). To improve monitoring, recognition and reporting of ATR more countries in the region have implemented or are considering national haemovigilance systems (Dahourou et al., 2012). In Namibia, The Blood Transfusion Service of Namibia (NAMBTS) is the only organisation authorised to collect, process and distribute blood and blood components for transfusion. Since 2006, NAMBTS has invested heavily in the development of guidelines and training for doctors and nurses in the appropriate clinical use of blood. Coupled with this focus on appropriate use, in 2008 NAMBTS launched a national haemovigilance system with a standardised reporting tool backed by clinical and laboratory investigations of all reported ATR. Under this system, healthcare workers (HCW) in Namibia who order or perform transfusions (primarily physicians and nurses) are responsible for voluntary reporting of ATR to NAMBTS by phone or via a paper-based system. Reportable ATR include allergic, acute haemolytic, febrile non-haemolytic reactions, sepsis due to bacterial contamination of the donor unit, transfusion-associated acute lung injury, transfusion-associated circulatory overload and transfusion-associated dyspnoea.

OBJECTIVE: To evaluate for changes in sexual behaviors associated with daily pill-use among MSM participating in a PrEP trial. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to receive tenofovir disoproxil fumarate or placebo at enrollment or after a 9-month delay and followed for 24 months. METHODS: 400 HIV-negative MSM reporting anal sex with a man in the past 12 months and meeting other eligibility criteria enrolled in San Francisco, Atlanta, and Boston. Sexual risk was assessed at baseline and quarterly visits using Audio Computer-Assisted Self-Interview. The association of pill-taking with sexual behavior was evaluated using logistic and negative-binomial regression for repeated measures. RESULTS: Overall indices of behavioral risk declined or remained stable during follow-up. Mean numbers of partners and proportion reporting unprotected anal sex (UAS) declined during follow-up (p<0.05), and mean UAS episodes remained stable. During the initial 9 months, changes in risk practices were similar in the group that began pills immediately vs. those in the delayed arm. These indices of risk did not differ significantly after initiation of pill-use in the delayed arm or continuation of study medication in the immediate arm. Use of poppers, amphetamines, and sexual performance-enhancing drugs were independently associated with one or more indices of sexual risk. CONCLUSIONS: There was no evidence of risk compensation among HIV-uninfected MSM in this clinical trial. Monitoring for risk compensation should continue now that PrEP has been shown to be efficacious in MSM and other populations and will be provided in open-label trials and other contexts.

OBJECTIVES: To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative MSM. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to immediate or delayed study drug (TDF [300mg orally/day] or placebo). METHODS: 400 healthy HIV-uninfected MSM reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events, adherence (pill count, Medical Event Monitoring System, [MEMS] and self-report), sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of adverse events and laboratory abnormalities. RESULTS: Study drug was initiated by 373 (93%) participants (186 TDF, 187 placebo), of whom 325 (87%) completed the final study visit. Of 2,428 adverse events reported among 334 (90%) participants, 2,366 (97%) were mild or moderate in severity.Frequencies of commonly reported adverse events did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (p=0.04); these reports were not associated with documented fractures or other objective findings. There were no Grade ≥3 creatinine elevations; Grade 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percent of study drug doses taken was 92% by pill count and 77% by MEMS. Seven seroconversions occurred; 4 on placebo and 3 among delayed arm participants not yet on study drug. CONCLUSION: Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.

BACKGROUND: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669 .).

OBJECTIVE: African American young adults are disproportionately affected by the HIV/AIDS epidemic and often unaware of their personal risk for HIV. Historically black colleges and universities (HBCUs) enroll 25% of college-educated African American young adults and can play an important role in HIV prevention. We examined HIV/AIDS knowledge of students at HBCUs to inform and strengthen our HIV prevention efforts at HBCUs. METHODS: African American undergraduate HBCU students completed online surveys assessing HIV/AIDS knowledge and behaviors, and we analyzed data to assess their knowledge and behaviors. RESULTS: A total of 1,051 of 1,230 surveys completed (85.4%) were analyzable. Eighty-two percent of students had average/high HIV knowledge scores. Seventy-nine percent of students surveyed perceived themselves to be at low risk for HIV infection; 64% of those who had at least two or more sex partners had not used a condom at last sex encounter. In the final model, significant independent effects were identified for average/high knowledge of HIV risk, including agreeing with assessing a potential partner's HIV risk by all of the five actions listed (adjusted odds ratio [AOR] = 2.7, 95% confidence interval [CI] 1.7, 4.3) and never using a needle to inject drugs (AOR=5.6, 95% CI 3.2, 9.7). CONCLUSIONS: Educating students about effectively assessing sex partner risk will improve HIV knowledge and prevention efforts at HBCUs.

We conducted a 10-year retrospective evaluation of the epidemiology and identification of Nocardia isolates submitted to the Centers for Disease Control and Prevention for antimicrobial susceptibility testing. The species most commonly identified were N. nova (28%), N. brasiliensis (14%), and N. farcinica (14%). Of 765 isolates submitted, 61% were resistant to sulfamethoxazole and 42% were resistant to trimethoprim-sulfamethoxazole.

BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.