Geolocation to Identify Online Study-Eligible Gay, Bisexual, and Men who have Sex with Men in Philadelphia, Pennsylvania.

BACKGROUND: Data collection and cleaning procedures to exclude bot-generated responses are used to maintain the data integrity of samples from online surveys. However, these procedures may be time-consuming and difficult to implement. Thus, we aim to evaluate the validity of a single-step geolocation algorithm for recruiting eligible gay, bisexual, and men who have sex with men in Philadelphia for an online study. METHODS: We used a 4-step approach, based on common practices for evaluating bot-generated and fraudulent responses, to assess the validity of participants' Qualtrics survey data as our referent standard. We then compared it to Qualtrics' single-step geolocation algorithm that used the MaxMind commercial database to map participants' Internet protocol address to their approximate location. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the single-step geolocation approach relative to the 4-step approach. RESULTS: There were 826 respondents who completed the survey and 440 (53%) were eligible for enrollment based on the 4-step approach. The single-step geolocation approach yielded a sensitivity of 91% (95% CI = 88%, 93%), specificity of 79% (95% CI = 74%, 83%), PPV of 83% (95% CI = 80%, 86%), and NPV of 88% (95% CI = 85%, 91%). CONCLUSIONS: Geolocation alone provided a moderately high level of agreement with the 4-step approach for identifying geographically eligible participants in the online sample, but both approaches may be subject to additional misclassification. Researchers may want to consider multiple procedures to ensure data integrity in online samples.

Perceived Barriers to and Facilitators of Long-Acting Injectable HIV PrEP Use Among Black, Hispanic/Latino, and White Gay, Bisexual, and Other Men Who Have Sex With Men.

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) was recently approved for HIV prevention as an alternative to daily oral PrEP. We explored preferences and attitudes toward LAI-PrEP among Black, Hispanic/Latino, and White gay, bisexual, and other men who have sex with men (GBM) using focus groups (n = 13) and in-depth interviews (n = 17). Participants expressed differing levels of interest in LAI-PrEP. While important benefits of LAI-PrEP included convenience, provider-facilitated PrEP discussion, and expansion of PrEP options, participants raised concerns about treatment efficacy and side effects, discomfort with needles/injections, cost, and frequency of clinic visits. Our findings highlight ongoing challenges with accessing HIV-prevention tools and provide guidance for developing strategies to enhance LAI-PrEP uptake among GBM.

Association of clinical signs of chorioamnionitis with histological chorioamnionitis and neonatal outcomes.

BACKGROUND: Chorioamnionitis is a risk factor for fetal and neonatal outcomes. Therefore, predicting histological chorioamnionitis (HCA) and neonatal outcomes using clinical parameters could be helpful in management and preventing morbidities. OBJECTIVE: To determine if parameters of clinical chorioamnionitis (CCA) would be associated with HCA and neonatal outcomes. STUDY DESIGN: In this cohort study using a retrospective design, we analyzed the performance of signs of CCA in predicting HCA, and neonatal outcomes. Data were extracted from the electronic health record for all neonates with documented CCA delivered at our institution from 2011 to 2016. We compared our findings based on the old ACOG definition of CCA and the new definition released in 2017 - maternal fever plus any of fetal tachycardia, maternal leukocytosis, and purulent vaginal discharge. Maternal tachycardia and uterine tenderness were removed from the new criteria. Neonatal laboratory samples on admission, 12 h and 24 h were used to define the three time points of neonatal suspected sepsis. RESULTS: There were 530 mothers-infant dyads with chorioamnionitis. Seventy-three were preterm, and 457 were term. Eighty-eight percent of the preterm mothers had CCA, and HCA was present in 62.5% of 72 preterm placentas. Preterm infants with placental HCA significantly had lower birth weight, gestational age, placental weight, and more infants with lower 5-minute Apgar scores, compared to those with no HCA. In preterm infants, maternal urinary tract infection was significantly associated with decreased odds for HCA (OR 0.22, CI 0.10 - 0.71). More preterm babies with suspected sepsis criteria at the 3 time points had HCA (all p ≤ .01). In the term cohort, 95.4% and 65.6% had CCA and HCA, respectively. In term infants (n = 457), maternal leukocytosis (p = .002) and prolonged rupture of membranes (PROM; p = 002) were associated with HCA. Suspected sepsis was associated with PROM (p = .04), HCA (p = .0001), and maternal leukocytosis (p ≤ .05) in at least 1 of the 3 time points. CONCLUSION: Though maternal leukocytosis was significantly associated with the presence of HCA in the term cohort, there were no CCA criteria that accurately predicted presence of HCA in either the preterm or the term infants.

Disparities of COVID-19 and HIV Occurrence Based on Neighborhood Infection Incidence in Philadelphia, Pennsylvania.

Objectives. To evaluate the occurrence of HIV and COVID-19 infections in Philadelphia, Pennsylvania, through July 2020 and identify ecological correlates driving racial disparities in infection incidence. Methods. For each zip code tabulation area, we created citywide comparison Z-score measures of COVID-19 cases, new cases of HIV, and the difference between the scores. Choropleth maps were used to identify areas that were similar or dissimilar in terms of disease patterning, and weighted linear regression models helped identify independent ecological predictors of these patterns. Results. Relative to COVID-19, HIV represented a greater burden in Center City Philadelphia, whereas COVID-19 was more apparent in Northeast Philadelphia. Areas with a greater proportion of Black or African American residents were overrepresented in terms of both diseases. Conclusions. Although race is a shared nominal upstream factor that conveys increased risk for both infections, an understanding of separate structural, demographic, and economic risk factors that drive the overrepresentation of COVID-19 cases in racial/ethnic communities across Philadelphia is critical. Public Health Implications. Difference-based measures are useful in identifying areas that are underrepresented or overrepresented with respect to disease occurrence and may be able to elucidate effective or ineffective mitigation strategies. (Am J Public Health. 2022;112(3):408-416. https://doi.org/10.2105/AJPH.2021.306538).

Countering the rise of syphilis: A role for doxycycline post-exposure prophylaxis?

Doxycycline post-exposure prophylaxis (PEP) holds the potential to mitigate increasing rates of syphilis among sexual minority men (SMM) in the US yet has received limited attention. Since evaluation of this intervention in actual populations is not currently feasible, we used agent-based models (ABM) to assess the population-level impact of this strategy. We adapted ABM of HIV and HPV transmission, representing a population of 10,230 SMM in Philadelphia, Pennsylvania, US. Parameter inputs were derived from the literature, and ABM outputs during the pre-intervention period were calibrated to local surveillance data. Intervention scenarios varied doxycycline uptake by 20, 40, 60, 80 and 100%, while assuming continued condom use and syphilis screening and treatment. Under each intervention scenario, we incorporated treatment adherence at the following levels: 0, 20, 40, 60, 80 and 100%. Long-term population impact of prophylactic doxycycline was measured using the cumulative incidence over the 10-year period and the percentage of infections prevented attributable to doxycycline at year 10. An uptake scenario of 20% with an adherence level of 80% would reduce the cumulative incidence of infections by 10% over the next decade, translating to 57 fewer cases per 1000 SMM. At year 10, under the same uptake and adherence level, 22% of infections would be prevented due to doxycycline PEP in the instances where condoms were not used or failed. Findings suggest that doxycycline PEP will have a modest impact on syphilis incidence when assuming a reasonable level of uptake and adherence. Doxycycline PEP may be most appropriate as a secondary prevention measure to condoms and enhanced syphilis screening for reducing infections among SMM.

Hospital-acquired Clostridioides difficile infection among patients at an urban safety-net hospital in Philadelphia: Demographics, neighborhood deprivation, and the transferability of national statistics.

OBJECTIVE: To investigate associations between healthcare-associated Clostridioides difficile infection and patient demographics at an urban safety-net hospital and compare findings with national surveillance statistics. METHODS: Study participants were selected using a case-control design using medical records collected between August 2014 and May 2018 at Hahnemann University Hospital in Philadelphia. Controls were frequency matched to cases by age and length of stay. Final sample included 170 cases and 324 controls. Neighborhood-level factors were measured using American Community Survey data. Multilevel models were used to examine infection by census tract, deprivation index, race/ethnicity, insurance type, referral location, antibiotic use, and proton-pump inhibitor use. RESULTS: Patients on Medicare compared to private insurance had 2.04 times (95% CI, 1.31-3.20) the odds of infection after adjusting for all covariables. Prior antibiotic use (2.70; 95% CI, 1.64-4.46) was also associated with infection, but race or ethnicity and referral location were not. A smaller proportion of hospital cases occurred among white patients (25% vs 44%) and patients over the age of 65 (39% vs 56%) than expected based on national surveillance statistics. CONCLUSIONS: Medicare and antibiotics were associated with Clostridioides difficile infection, but evidence did not indicate association with race or ethnicity. This finding diverges from national data in that infection is higher among white people compared to nonwhite people. Furthermore, a greater proportion of hospital cases were aged <65 years than expected based on national data. National surveillance statistics on CDI may not be transportable to safety-net hospitals, which often disproportionately serve low-income, nonwhite patients.

Modeling HPV vaccination scale-up among urban young men who have sex with men in the context of HIV.

INTRODUCTION: Young men who have sex with men (YMSM) are at high risk to contract human papillomavirus (HPV). While an effective vaccination exists, its use among YMSM is markedly lower compared to non-MSM and women. This study compares scaling up HPV vaccination in conjunction with other prevention strategies. METHODS: An agent-based model of urban YMSM (≤26 years of age) reflective of the demography of Philadelphia, PA, simulated for up to ten years of follow-up to examine anal and oral transmission of the HPV genotypes covered in the nonavalent (9v) vaccine: 6, 11, 16, 18, 31, 33, 45, 52, 58. Starting HPV prevalences ranged from a high of 18% (type 6) to a low of 6% (type 31); overall 65% of individuals carried any HPV genotype. Simulated levels of vaccination were ranged from 0% to 13% (present-day level), 25%, 50%, 80% (Healthy People 2020 target), and 100% in conjunction with condom use and HIV seroadaptive practices. The primary outcome was the relative reduction in HPV infection. RESULTS: Compared to present-day vaccination levels (13%), scaling-up vaccination led to expected declines in 10-year post-simulation HPV prevalence. Anal HPV (any 9v types) declined by 9%, 27%, 46%, and 58% at vaccination levels of 25%, 50%, 80%, and 100%, respectively. Similarly, oral HPV (any 9v types) declined by 11%, 33%, 57%, and 71% across the same levels of vaccine uptake. Comparing the prevention strategies, condoms blocked the greatest number of anal transmissions when vaccination was at or below present-day levels. For oral transmission, vaccination was superior to condom use at all levels of coverage. CONCLUSIONS: Public health HPV preventions strategies should continue to emphasize the complementary roles of condoms and vaccination, especially for preventing oral infection. Improving vaccination coverage will ultimately have the greatest impact on reducing HPV infection among YMSM.

Four Decades of Epidemiologic Science on HIV Infection and Disease, and Its Impact on Public Health Practice and Policy for Sexual and Gender Minority Persons.

Even at the cusp of the second decade of the new millennia, HIV continues to be a significant public health challenge for sexual and gender minorities (SGM). Men who have sex with men and transgender women, in particular, continue to report higher rates of HIV incidence compared to their heterosexual counterparts, while facing significant barriers to comprehensive sexual healthcare. In Delaware, HIV infection impacts a substantial number of individuals with approximately 14.5 incident cases per 100,000. This ranks Delaware as the 14th highest for HIV incidence among U.S. states. However, the largest healthcare provider in Delaware, Christiana Care Health System, has created many health initiatives to support the health needs of SGM and those living with HIV. The current sustained rate of HIV infection indicates the need for enhanced epidemiologic work to identify HIV cases in subgroups of diverse sexuality and gender identity, collaboration within and across research institution and community organizations, as well as engagement in creative solutions that target the multiple levels of factors contributing to HIV incidence. In addition, it is imperative that local agencies and health organizations continue to support these communities of SGM individuals during the current sociopolitical climate of the national U.S. government.

Bias Adjustment Techniques Are Underutilized in HIV Sexual Risk Estimation: A Systematic Review.

Background: Valid measurement of determinants of HIV infection among men who have sex with men (MSM) is critical for intervention planning and resource allocation. However, sexual minority research concerning HIV risk often relies on proxy exposures of sexual behaviors such as sexual orientation and partner gender. Inferring high risk sexual behaviors (i.e., condomless anal intercourse) from these proxies inaccurately captures HIV risk, but few studies have attempted to correct for this bias. Methods: We performed a systematic review of methodological practices for estimating risk of HIV infection among MSM. Results: We identified 32 studies in which high risk sexual behavior was assessed: 82% (n = 26) measured and used sexual risk behaviors (e.g., condomless anal intercourse or sexual positioning) to assess risk of HIV infection; 9% (n = 3) used proxy measures; and 9% (n = 3) used both behavior and proxy variables. Various treatments of misclassification reported by investigators included the following: 82% (n = 26) discussed misclassification of sexual behavior as a potential limitation; however, among these studies, no attempts were made to correct misclassification; 12% (n = 4) did not report exposure misclassification, and 6% (n = 2) explicitly considered this information bias and conducted a Bayesian approach to correct for misclassification. Conclusions: Our systematic review indicates that a majority of studies engaging in collecting primary data have taken additional steps to acquire detailed information regarding sexual risk behaviors. However, reliance on population-based surveys may still lead to potentially biased estimates. Thus, bias analytic techniques are potential tools to control for any suspected biases.

An Exploration of Factors Impacting Preexposure Prophylaxis Eligibility and Access Among Syringe Exchange Users.

BACKGROUND: In 2015, approximately 50,000 new HIV infections occurred in the United States, 2,400 of which were attributable to injection drug use. Preexposure prophylaxis (PrEP) has the potential to curb HIV acquisition; however, uptake remains low among persons who inject drugs (PWID). The purpose of the study is to describe PrEP eligibility, willingness to use PrEP, and ability to access PrEP among PWID recruited from a pilot program that paired screening and treatment of sexually transmitted infections with mobile syringe exchange program (SEP) services. METHODS: Between 2015 and 2016, 138 PWID 18 years or older were recruited from a mobile SEP in Camden, New Jersey. Participants completed a survey assessing sociodemographics and HIV risk and underwent chlamydia and gonorrhea screening. Centers for Disease Control clinical guidelines were used to calculate PrEP eligibility. Differences by sex were examined using inferential statistics. RESULTS: Most women (95.4%) and men (84.5%) were considered PrEP eligible (P < 0.04). More women than men were willing to take PrEP (88.9% vs. 71.0%; P < 0.02). Participants reported substantial barriers to PrEP including feeling embarrassed (45.0%) or anxious (51.6%) about taking PrEP, nondisclosure to partners (51.4%), limited engagement with health care providers where PrEP might be provided (43.8%), and lacking health insurance (32.9%). CONCLUSIONS: Despite reporting behavior that warrants the use of PrEP to prevent HIV and finding the concept acceptable, PWID face multiple barriers to PrEP access. Without tailored interventions to promote PrEP, uptake will likely remain suboptimal. Packaging PrEP with SEP services could provide a viable option for reaching eligible and interested PWID.

Mental health disorders mediate association of sexual minority identity with cardiovascular disease.

BACKGROUND: Little is known about cardiovascular health disparities for lesbian, gay, or bisexual (LGB) persons and whether these disparities are mediated by mental health disorders due to sexual minority stress. We hypothesize LGB identity is associated with an increased risk of cardiovascular disease (CVD) and that major depressive disorder (MDD) and generalized anxiety disorders (GAD) may mediate this association. METHODS: The National Epidemiologic Survey on Alcohol and Related Conditions is a longitudinal, nationally-representative study of non-institutionalized U.S. adults. We cross-sectionally analyzed the second wave data (2004-2005) comparing 577 self-identified LGB persons to 33,598 heterosexuals. Multiple logistic regression modeling and mediation analysis (the product of coefficients approach) were performed. RESULTS: LGB persons had significantly higher CVD prevalence [adjusted odds ratio (AOR): 1.5, 95% CI: 1.2-1.9], and were more likely to be diagnosed with MDD (AOR: 1.9, 1.8-2.1), GAD (AOR: 2.2, 1.9-2.4), or co-occurring MDD and GAD (AOR: 2.2, 2.0-2.5). MDD, GAD, and co-occurrence of MDD and GAD significantly mediated 14.3%, 22.2%, and 33.3% of the association of LGB status with increased CVD prevalence, respectively. CONCLUSIONS: Our findings identified a 50% increased CVD prevalence among LGB persons and this increased risk was mediated in part by MDD and GAD, both being more prevalent in sexual minority adults.

The Effect of PrEP on HIV Incidence Among Men Who Have Sex With Men in the Context of Condom Use, Treatment as Prevention, and Seroadaptive Practices.

BACKGROUND: HIV preexposure prophylaxis (PrEP) is an effective tool in preventing HIV infection among high-risk men who have sex with men (MSM). It is unknown how effective PrEP is in the context of other implemented HIV prevention strategies, including condom use, seroadaption, and treatment as prevention (TasP). We evaluate the impact of increasing uptake of PrEP in conjunction with established prevention strategies on HIV incidence in a high-risk population of MSM through simulation. METHODS: Agent-based simulation models representing the sexual behavior of high-risk, urban MSM in the United States over the period of 1 year were used to evaluate the effect of PrEP on HIV infection rates. Simulations included data for 10,000 MSM and compared increasing rates of PrEP uptake under 8 prevention paradigms: no additional strategies, TasP, condom use, seroadaptive behavior, and combinations thereof. RESULTS: We observed a mean of 103.2 infections per 10,000 MSM in the absence of any prevention method. PrEP uptake at 25% without any additional prevention strategies prevented 30.7% of infections. In the absence of PrEP, TasP, condom use, and seroadaptive behavior independently prevented 27.1%, 48.8%, and 37.7% of infections, respectively, and together prevented 72.2%. The addition of PrEP to the 3 aforementioned prevention methods, at 25% uptake, prevented an additional 5.0% of infections. CONCLUSIONS: To achieve a 25% reduction in HIV infections by 2020, HIV prevention efforts should focus on significantly scaling up access to PrEP in addition to HIV testing, access to antiretroviral therapy, and promoting condom use.

Does Employment-Related Resilience Affect the Relationship between Childhood Adversity, Community Violence, and Depression?

Depression is a barrier to employment among low-income caregivers receiving Temporary Assistance for Needy Families (TANF), and adverse childhood experiences (ACEs) and exposure to community violence (ECV) are often associated with depression. Using baseline data of 103 TANF caregivers of young children of the Building Wealth and Health Network Randomized Controlled Trial Pilot, this study investigated associations of two forms of employment-related resilience-self-efficacy and employment hope-with exposure to adversity/violence and depression, measured by the Center for Epidemiologic Studies Depression (CES-D) short form. Using contingency table analysis and regression analysis, we identified associations between ACEs and depression [OR = 1.70 (1.25-2.32), p = 0.0008] and having high levels of ECV with a 6.9-fold increased risk for depression when compared with those without ECV [OR = 6.86 (1.43-33.01), p = 0.02]. While self-efficacy and employment hope were significantly associated with depression, neither resilience factor impacted the association of ACE level and depression, whereas self-efficacy and employment hope modestly reduced the associations between ECV and depression, 13 and 16%, respectively. Results suggest that self-efficacy and employment hope may not have an impact on the strong associations between adversity, violence, and depression.

Bayesian Approaches to Racial Disparities in HIV Risk Estimation Among Men Who Have Sex with Men.

BACKGROUND: Men who have sex with men (MSM) continue to be overrepresented for new HIV infections compared with non-MSM. This disparity becomes even more alarming when considering racial groups. We describe the race-specific effects in HIV prevalence among MSM relative to non-MSM and explore the causes of disagreement among estimates. METHODS: We used data from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative longitudinal survey conducted in the US Bayesian learning corrected for potential misclassification of MSM status and adjusted for residual confounding, hypothesized to explain the MSM racial disparity in HIV. We articulated the structure and strength of the latent confounders that would make race-specific risk gradients equivalent. RESULTS: Compared with non-MSM, the adjusted prevalence odds ratio (POR) and 95% credible interval for black MSM having self-reported HIV infection was 5.8 (2.0, 16), while the POR for white MSM was 12 (4.2, 31). For all MSM, the POR for HIV infection was 9.3 (3.6, 23) with black men having 2.6 times the odds of prevalent infection compared with white men. CONCLUSIONS: The observed race-specific associations in MSM are likely not due to misclassification alone, but represent a constellation of factors that differ between racial groups. We recommend specific risk factors in surveys needed to further identify the behavioral characteristics that lead to the observed differences when the estimates are stratified by race.

The Building Wealth and Health Network: methods and baseline characteristics from a randomized controlled trial for families with young children participating in temporary assistance for needy families (TANF).

BACKGROUND: Families with children under age six participating in the Temporary Assistance for Needy Families Program (TANF) must participate in work-related activities for 20 h per week. However, due to financial hardship, poor health, and exposure to violence and adversity, families may experience great difficulty in reaching self-sufficiency. The purpose of this report is to describe study design and baseline findings of a trauma-informed financial empowerment and peer support intervention meant to mitigate these hardships. METHODS: We conducted a randomized controlled trial of a 28-week intervention called Building Wealth and Health Network to improve financial security and maternal and child health among caregivers participating in TANF. Participants, recruited from County Assistance offices in Philadelphia, PA, were randomized into two intervention groups (partial and full) and one control group. Participants completed questionnaires at baseline to assess career readiness, economic hardship, health and wellbeing, exposure to adversity and violence, and interaction with criminal justice systems. RESULTS: Baseline characteristics demonstrate that among 103 participants, there were no significant differences by group. Mean age of participants was 25 years, and youngest child was 30 months. The majority of participants were women (94.2 %), never married (83.5 %), unemployed (94.2 %), and without a bank account (66.0 %). Many reported economic hardship (32.0 % very low household food secure, 65.0 % housing insecure, and 31.1 % severe energy insecure), and depression (57.3 %). Exposure to adversity was prevalent, where 38.8 % reported four or more Adverse Childhood Experiences including abuse, neglect and household dysfunction. In terms of community violence, 64.7 % saw a seriously wounded person after an incident of violence, and 27.2 % had seen someone killed. Finally, 14.6 % spent time in an adult correctional institution, and 48.5 % of the fathers of the youngest child spent time in prison. CONCLUSIONS: Baseline findings demonstrate that caregivers participating in TANF have suffered significant childhood adversity, adult violence exposure, and poverty-related stressors that can limit workforce success. High prevalence of housing and food insecurity, exposure to adversity, violence and criminal justice systems demands comprehensive programming to support families. Trauma-informed approaches to career readiness such as the Building Wealth and Health Network offer opportunities for potential success in the workforce. TRIAL REGISTRATION: This study is retrospectively registered with ClinicalTrials.gov. The Identifier is: NCT02577705 The Registration date is October 13, 2015.

Bayesian Correction of Misclassification of Pertussis in Vaccine Effectiveness Studies: How Much Does Underreporting Matter?

Diagnosis of pertussis remains a challenge, and consequently research on the risk of disease might be biased because of misclassification. We quantified this misclassification and corrected for it in a case-control study of children in Philadelphia, Pennsylvania, who were 3 months to 6 years of age and diagnosed with pertussis between 2011 and 2013. Vaccine effectiveness (VE; calculated as (1 - odds ratio) × 100) was used to describe the average reduction in reported pertussis incidence resulting from persons being up to date on pertussis-antigen containing vaccines. Bayesian techniques were used to correct for purported nondifferential misclassification by reclassifying the cases per the 2014 Council of State and Territorial Epidemiologists pertussis case definition. Naïve VE was 50% (95% confidence interval: 16%, 69%). After correcting for misclassification, VE ranged from 57% (95% credible interval: 30, 73) to 82% (95% credible interval: 43, 95), depending on the amount of underreporting of pertussis that was assumed to have occurred in the study period. Meaningful misclassification was observed in terms of false negatives detected after the incorporation of infant apnea to the 2014 case definition. Although specificity was nearly perfect, sensitivity of the case definition varied from 90% to 20%, depending on the assumption about missed cases. Knowing the degree of the underreporting is essential to the accurate evaluation of VE.

To Be or Not to Be: Bayesian Correction for Misclassification of Self-reported Sexual Behaviors Among Men Who Have Sex with Men.

BACKGROUND: Inferring sexual behavior of a stigmatized minority through self-reported sexual identity is subject to misclassification and can lead to biased results. We quantify the degree of this misclassification and perform a Bayesian correction of the risk of HIV infection in relation to self-reported sexual behavior. METHODS: Sensitivity and specificity of self-reported men who have sex with men in ascertaining sexual behavior was derived from validation data, as was the informative prior on the association of same-sex behavior with self-reported HIV infection. Using these priors, we performed two separate Bayesian analyses of National Epidemiologic Survey on Alcohol and Related Conditions data for the odds of self-reported HIV positivity, adjusting for differential misclassification of self-reported same-sex behavior indicated by either partner gender or sexual identity. RESULTS: We found differential exposure misclassification with specificity exceeding sensitivity, and higher misclassification rates based on sexual identity compared with partner gender. Sexual identity and partner gender displayed different associations with HIV infection in the raw data but these became virtually identical when adjusted for estimates of misclassification of sexual behavior by these two indicators. The estimate of prevalence of same-sex behavior associated with an elevated risk of HIV infection decreased after adjustment for misclassification. CONCLUSIONS: Studies of risk due to same-sex behavior are likely biased when they rely on self-identification for ascertainment of risk factors, especially when self-reported identity is used. The implications of our findings on risk modeling cannot be assumed to be trivial due to substantial shifts in distributions of risk and prevalence of exposure.

Choice of measures of vaccination and estimates of risk of pediatric pertussis.

BACKGROUND: Vaccination uptake at the individual level can be assessed in a variety of ways, including traditional measures of being up-to-date (UTD), measures of UTD that consider dose timing, like age-appropriate vaccination, and risk reduction from individual doses. This analysis compared methods of operationalizing vaccination uptake and corresponding risk of pertussis infection. METHODS: City-wide case-control study of children in Philadelphia aged 3 months through 6 years, between 2001 and 2013. Multiple logistic regression was used to isolate the independent effects of each measure of vaccination uptake and the corresponding relative odds of pertussis. RESULTS: Being UTD on vaccinations was associated with a 52% reduction in risk of pertussis (OR 0.48, 95% CI: 0.34, 0.69). Evaluation of delayed receipt of vaccine versus on-time UTD yielded similar results. There was a decrease in risk of pertussis for each additional dose received with the greatest reduction in pertussis infection observed from the first (OR 0.48, 95% CI: 0.28, 0.83) and second dose (OR 0.17, 95% CI: 0.08, 0.34). Additional doses conferred minimal additional protection in this age group. CONCLUSION: Examining vaccination status by individual doses may offer improved predictive capacity for identifying children at risk for pertussis infection compared to the traditional UTD measure.

Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine.

Chronic HCV is a surreptitious disease currently affecting approximately 3% of the world's population that can lead to liver failure and cancer decades following initial infection. However, there are currently no vaccines available for the prevention of chronic HCV. From patients who acutely resolve HCV infection, it is apparent that a strong and broad cytotoxic T lymphocyte (CTL) response is important in HCV clearance. DNA vaccines are naked plasmid DNA molecules that encode pathogen antigens to induce a pathogen-specific immune response. They are inexpensive to produce and have an excellent safety profile in animals and humans. Additionally, DNA vaccines are able to induce strong CTL responses, making them well-suited for an HCV vaccine. We aimed to maximize vaccine recipients' opportunity to induce a broad T cell response with a novel antigenic sequence, multi-antigen vaccine strategy. We have generated DNA plasmids encoding consensus sequences of HCV genotypes 1a and 1b non-structural proteins NS3/4a, NS4b, NS5a, and NS5b. Rhesus macaques were used to study the immunogenicity of these constructs. Four animals were immunized 3 times, 6 weeks apart, at a dose of 1.0mg per antigen construct, as an intramuscular injection followed by in vivo electroporation, which greatly increases DNA uptake by local cells. Immune responses were measured 2 weeks post-immunization regimen (PIR) in immunized rhesus macaques and showed a broad response to multiple HCV nonstructural antigens, with up to 4680 spot-forming units per million peripheral blood mononuclear cells (PBMCs) as measured by Interferon-γ ELISpot. In addition, multiparametric flow cytometry detected HCV-specific CD4+ and CD8+ T cell responses by intracellular cytokine staining and detected HCV-specific CD107a+/GrzB+ CD8+ T cells indicating an antigen specific cytolytic response 2 weeks PIR compared with baseline measurements. At the final study time point, 6 weeks PIR, HCV-specific CD45RA- memory-like T cells remained detectable in peripheral blood. Data presented in this manuscript support the notion that vaccine immunogenicity studies using a macaque model can be used to depict key anti-HCV nonstructural antigenic cellular immune responses and support the development of DNA-based prophylactic HCV vaccines.