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Optimizing Screening for HIV.

ABSTRACT: Background:The HIV epidemic is unevenly distributed throughout the United States, even within neighborhoods. This study evaluated how effectively current testing approaches reached persons at risk for HIV infection across San Diego (SD) County, California. Methods:HIV case and testing data, sexually transmitted infection (STI) data, and sociodemographic data for SD County were collected from the SD Health and Human Services Agency and the "Early Test" community-based HIV screening program between 1998 and 2016. Relationships between HIV diagnoses, HIV prevalence, and STI diagnoses with screening at the ZIP code level were evaluated. Results:Overall, 379 074 HIV tests were performed. The numbers of HIV tests performed on persons residing in a ZIP code or region overall strongly correlated with prevalent HIV cases (R 2 = .714), new HIV diagnoses (R 2 = .798), and STI diagnoses (R 2 = .768 [chlamydia], .836 [gonorrhea], .655 [syphilis]) in those regions. ZIP codes with the highest HIV prevalence had the highest number of tests per resident and fewest number of tests per diagnosis. Even though most screening tests occurred at fixed venues located in high-prevalence areas, screening of residents from lower-prevalence areas was mostly proportional to the prevalence of HIV and rates of new HIV and STI diagnoses in those locales. Conclusions:This study supported the ability of a small number of standalone testing centers to reach at-risk populations dispersed across SD County. These methods can also be used to highlight geographic areas or demographic segments that may benefit from more intensive screening.

SUBMITTER: Chaillon A

PROVIDER: S-EPMC7009491 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Optimizing Screening for HIV.

Chaillon Antoine A Hoenigl Martin M Freitas Lorri L Feldman Haruna H Tilghman Winston W Wang Lawrence L Smith Davey D Little Susan S Mehta Sanjay R SR

Open forum infectious diseases 20200119 2

<h4>Background</h4>The HIV epidemic is unevenly distributed throughout the United States, even within neighborhoods. This study evaluated how effectively current testing approaches reached persons at risk for HIV infection across San Diego (SD) County, California.<h4>Methods</h4>HIV case and testing data, sexually transmitted infection (STI) data, and sociodemographic data for SD County were collected from the SD Health and Human Services Agency and the "Early Test" community-based HIV screening ...[more]

PMID: 32055638

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Project description:BACKGROUND: Human immunodeficiency virus (HIV) is the etiological agent in AIDS and related diseases. The aspartyl protease encoded by the 5' portion of the pol gene is responsible for proteolytic processing of the gag-pol polyprotein precursor to yield the mature capsid protein and the reverse transcriptase and integrase enzymes. The HIV protease (HIV-1Pr) is considered an attractive target for designing inhibitors which could be used to tackle AIDS and therefore it is still the object of a number of investigations. RESULTS: A recombinant human immunodeficiency virus type 1 protease (HIV-1Pr) was overexpressed in Escherichia coli cells as a fusion protein with bacterial periplasmic protein dithiol oxidase (DsbA) or glutathione S-transferase (GST), also containing a six-histidine tag sequence. Protein expression was optimized by designing a suitable HIV-1Pr cDNA (for E. coli expression and to avoid autoproteolysis) and by screening six different E. coli strains and five growth media. The best expression yields were achieved in E. coli BL21-Codon Plus(DE3)-RIL host and in TB or M9 medium to which 1% (w/v) glucose was added to minimize basal expression. Among the different parameters assayed, the presence of a buffer system (based on phosphate salts) and a growth temperature of 37°C after adding IPTG played the main role in enhancing protease expression (up to 10 mg of chimeric DsbA:HIV-1Pr/L fermentation broth). GST:HIVPr was in part (50%) produced as soluble protein while the overexpressed DsbA:HIV-1Pr chimeric protein largely accumulated in inclusion bodies as unprocessed fusion protein. A simple refolding procedure was developed on HiTrap Chelating column that yielded a refolded DsbA:HIV-1Pr with a > 80% recovery. Finally, enterokinase digestion of resolubilized DsbA:HIV-1Pr gave more than 2 mg of HIV-1Pr per liter of fermentation broth with a purity ? 80%, while PreScission protease cleavage of soluble GST:HIVPr yielded ~ 0.15 mg of pure HIV-1Pr per liter. CONCLUSIONS: By using this optimized expression and purification procedure fairly large amounts of good-quality HIV-1Pr recombinant enzyme can be produced at the lab-scale and thus used for further biochemical studies.

Project description:BackgroundMindstep is an app that aims to improve dementia screening by assessing cognition and risk factors. It considers important clinical risk factors, including prodromal symptoms, mental health disorders, and differential diagnoses of dementia. The 9-item Patient Health Questionnaire for depression (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) are widely validated and commonly used scales used in screening for depression and anxiety disorders, respectively. Shortened versions of both (PHQ-2/GAD-2) have been produced.ObjectiveWe sought to develop a method that maintained the brevity of these shorter questionnaires while maintaining the better precision of the original questionnaires.MethodsSingle questions were designed to encompass symptoms covered in the original questionnaires. Answers to these questions were combined with PHQ-2/GAD-2, and anonymized risk factors were collected by Mindset4Dementia from 2235 users. Machine learning models were trained to use these single questions in combination with data already collected by the app: age, response to a joke, and reporting of functional impairment to predict binary and continuous outcomes as measured using PHQ-9/GAD-7. Our model was developed with a training data set by using 10-fold cross-validation and a holdout testing data set and compared to results from using the shorter questionnaires (PHQ-2/GAD-2) alone to benchmark performance.ResultsWe were able to achieve superior performance in predicting PHQ-9/GAD-7 screening cutoffs compared to PHQ-2 (difference in area under the curve 0.04, 95% CI 0.00-0.08, P=.02) but not GAD-2 (difference in area under the curve 0.00, 95% CI -0.02 to 0.03, P=.42). Regression models were able to accurately predict total questionnaire scores in PHQ-9 (R2=0.655, mean absolute error=2.267) and GAD-7 (R2=0.837, mean absolute error=1.780).ConclusionsWe app-adapted PHQ-4 by adding brief summary questions about factors normally covered in the longer questionnaires. We additionally trained machine learning models that used the wide range of additional information already collected in Mindstep to make a short app-based screening tool for affective disorders, which appears to have superior or equivalent performance to well-established methods.

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Optimizing Screening for HIV.

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Optimizing Screening for HIV.

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