HIV Diagnoses Through Partner Services in the United States in 2019 and Opportunities for Improvement.

HIV partner services (HIV PS) is an effective strategy for diagnosing HIV infection. Sex/needle-sharing partners of individuals diagnosed with HIV are notified about potential exposure and offered HIV testing and other services. We assessed the HIV PS contribution to HIV diagnoses in the United States and assessed priority areas for improvements. National HIV Monitoring and Evaluation Partner Services and case surveillance data reported to the Centers for Disease Control and Prevention for 2019 were used for this analysis. The percentage of all new diagnoses that HIV PS programs reported is described nationally and by state. Linkage to HIV medical care among newly diagnosed partners is described. Potential increases in diagnosing HIV infection are assessed by HIV PS step to identify priority areas for improvement. HIV PS contributed 1214 of 35,164 (3.5%) of all diagnoses nationally in 2019, and contributions ranged from 0% to 31.8% by state. Of partners tested with nonmissing data, 22.7% were newly diagnosed. An estimated 1692 new partner diagnoses were lost during HIV PS steps. Steps resulting in the highest losses included index patients not being interviewed, partners not being tested for HIV, and index patients not being located. Seventy-two percent of partners newly diagnosed with HIV were linked to HIV medical care. HIV PS is an effective strategy for diagnosing HIV, and a high percent of sex/needle-sharing partners was newly diagnosed with HIV. Expanded HIV PS in some states and targeted improvements in HIV PS steps can enhance the contribution of HIV PS toward achieving national goals.

Adults Aged ≥50 Years Reached by the Centers for Disease Control and Prevention's HIV Testing Programs in the United States and US Dependent Areas, 2019.

OBJECTIVES: Older adults represent nearly half of people living with HIV in the United States. The objective of this analysis was to describe HIV testing, demographic characteristics, and risks of adults aged ≥50 years (older adults) reached in 2019 by HIV testing programs funded by the Centers for Disease Control and Prevention (CDC). METHODS: We collected data from 101 CDC-funded community-based organizations and 61 health departments. All funding recipients submitted deidentified program service data for 2019 through a secure online CDC-supported system. We used multivariable robust Poisson regression to assess the association between demographic and risk characteristics and the proportion of tests that resulted in a new diagnosis. We also assessed the proportion of people who received a positive test result, were linked to HIV medical care, and were interviewed for partner services. RESULTS: During 2019, among 2 452 507 CDC-funded HIV tests provided in the United States, 412 164 (16.8%) were provided to older adults. Among the 1059 (0.26% positivity) older adults with newly diagnosed HIV infection for whom we had data, 582 (68.4%) were linked to HIV medical care within 30 days of diagnosis and 494 (72.1%) were interviewed for partner services. Among the 2858 older adults with previously diagnosed HIV infection, 1321 (46.2%) reported not being in HIV medical care at the time of the test; of those with linkage data, 425 (49.9%) were linked to HIV medical care within 30 days of testing HIV positive. CONCLUSIONS: More rapid disease progression and higher morbidity and mortality rates among older adults suggest that services are needed to ensure early diagnosis, rapid linkage, and interview for partner services.

The Epidemiology of Human Immunodeficiency Virus Infection and Care among Adult and Adolescent Females in the United States, 2008-2012.

OBJECTIVE: We sought to determine epidemiological patterns in diagnoses of human immunodeficiency virus (HIV) infection and prevalence among females by age, race/ethnicity and transmission category, and essential steps in the continuum of HIV care. METHODS: Using data from the National HIV Surveillance System, we estimated the number of females aged 13 years or older diagnosed with HIV infection in 2008 through 2012 and living with HIV at the end of 2011 in the United States. We determined percentages of females linked to care, retained in care, and virally suppressed in 18 jurisdictions with complete reporting of CD4 and viral load test results. RESULTS: From 2008 to 2012, the estimated rate of HIV diagnoses among females decreased from 9.3 to 6.9 per 100,000 (-7.1% per year; 95% confidence interval [CI], -7.9, -6.3). In 2012, the diagnosis rate was highest among Blacks/African Americans (35.7), followed by Hispanics or Latinos (6.4), and Native Hawaiian Other Pacific Islander (5.1), and lowest among Whites (1.8). Most females diagnosed in 2012 were linked to care within 3 months of diagnosis (82.5%). About one-half (52.4%) of females living with HIV in 2011 received ongoing care in 2011 and 44.3% had a suppressed viral load. Viral suppression was lower among American Indian/Alaska Native (29.7%) and Black/African American (41.6%) compared with White females (46.5%). The percentage in care and with viral suppression was lower among younger compared with older females. CONCLUSION: HIV diagnoses continue to decrease among females; however, disparities exist in HIV burden and viral suppression. Improvements in care and treatment outcomes are needed for all women with particular emphasis on younger women.

Comparison of Rates of Death Having any Death-Certificate Mention of Heart, Kidney, or Liver Disease Among Persons Diagnosed with HIV Infection with those in the General US Population, 2009-2011.

OBJECTIVE: Compare age-adjusted rates of death due to liver, kidney, and heart diseases during 2009-2011 among US residents diagnosed with HIV infection with those in the general population. METHODS: Numerators were numbers of records of multiple-cause mortality data from the national vital statistics system with an ICD-10 code for the disease of interest (any mention, not necessarily the underlying cause), divided into those 1) with and 2) without an additional code for HIV infection. Denominators were 1) estimates of persons living with diagnosed HIV infection from national HIV surveillance system data and 2) general population estimates from the US Census Bureau. We compared age-adjusted rates overall (unstratified by sex, race/ethnicity, or region of residence) and stratified by demographic group. RESULTS: Overall, compared with the general population, persons diagnosed with HIV infection had higher age-adjusted rates of death reported with hepatitis B (rate ratio [RR]=42.6; 95% CI: 34.7-50.7), hepatitis C (RR=19.4; 95% CI: 18.1-20.8), liver disease excluding hepatitis B or C (RR=2.1; 95% CI: 1.8-2.3), kidney disease (RR=2.4; 95% CI: 2.2-2.6), and cardiomyopathy (RR=1.9; 95% CI: 1.6-2.3), but lower rates of death reported with ischemic heart disease (RR=0.6; 95% CI: 0.6-0.7) and heart failure (RR=0.8; 95% CI: 0.6-0.9). However, the differences in rates of death reported with the heart diseases were insignificant in some demographic groups. CONCLUSION: Persons with HIV infection have a higher risk of death with liver and kidney diseases reported as causes than the general population.

Development of the Lymphoma Enterprise Architecture Database: a caBIG Silver level compliant system.

Lymphomas are the fifth most common cancer in United States with numerous histological subtypes. Integrating existing clinical information on lymphoma patients provides a platform for understanding biological variability in presentation and treatment response and aids development of novel therapies. We developed a cancer Biomedical Informatics Grid (caBIG) Silver level compliant lymphoma database, called the Lymphoma Enterprise Architecture Data-system (LEAD), which integrates the pathology, pharmacy, laboratory, cancer registry, clinical trials, and clinical data from institutional databases. We utilized the Cancer Common Ontological Representation Environment Software Development Kit (caCORE SDK) provided by National Cancer Institute's Center for Bioinformatics to establish the LEAD platform for data management. The caCORE SDK generated system utilizes an n-tier architecture with open Application Programming Interfaces, controlled vocabularies, and registered metadata to achieve semantic integration across multiple cancer databases. We demonstrated that the data elements and structures within LEAD could be used to manage clinical research data from phase 1 clinical trials, cohort studies, and registry data from the Surveillance Epidemiology and End Results database. This work provides a clear example of how semantic technologies from caBIG can be applied to support a wide range of clinical and research tasks, and integrate data from disparate systems into a single architecture. This illustrates the central importance of caBIG to the management of clinical and biological data.

Mutational analyses of packaging signals in influenza virus PA, PB1, and PB2 genomic RNA segments.

The influenza A virus genome consists of eight negative-sense RNA segments that must each be packaged to produce an infectious virion. We have previously mapped the minimal cis-acting regions necessary for efficient packaging of the PA, PB1, and PB2 segments, which encode the three protein subunits of the viral RNA polymerase. The packaging signals in each of these RNAs lie within two separate regions at the 3' and 5' termini, each encompassing the untranslated region and extending up to 80 bases into the adjacent coding sequence. In this study, we introduced scanning mutations across the coding regions in each of these RNA segments in order to finely define the packaging signals. We found that mutations producing the most severe defects were confined to a few discrete 5' sites in the PA or PB1 coding regions but extended across the entire (80-base) 5' coding region of PB2. In sequence comparisons among more than 580 influenza A strains from diverse hosts, these highly deleterious mutations were each found to affect one or more conserved bases, though they did not all lie within the most broadly conserved portions of the regions that we interrogated. We have introduced silent and conserved mutations to the critical packaging sites, which did not affect protein function but impaired viral replication at levels roughly similar to those of their defects in RNA packaging. Interestingly, certain mutations showed strong tendencies to revert to wild-type sequences, which implies that these putative packaging signals are critical for the influenza life cycle.

A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction.

Crk-associated substrate (CAS), a 130-kDa adaptor protein, was discovered as a tyrosine kinase substrate of Src that was important to cellular motility and actin filament formation. As the tyrosine kinase Src is utilized by the 5-hydroxytryptamine (5-HT)(2A) receptor in arterial contraction, we tested the hypothesis that CAS was integral to 5-HT(2A) receptor-mediated vasoconstriction. Rat thoracic aorta was used as a model of the arterial 5-HT(2A) receptor. Western and immunohistochemistry analyses validated the presence of CAS in the aorta, and tissue bath experiments demonstrated reduction of contraction to 5-HT (13.5 +/- 5% control maximum) and the 5-HT(2) receptor agonist alpha-methyl-5-HT (6 +/- 2% maximum) by latrunculin B (10(-6) mol/l), an actin disruptor. In aorta contracted with 5-HT (10(-5) mol/l), tyrosine phosphorylation (Tyr410) of CAS was significantly increased (approximately 225%), and both contraction and CAS phosphorylation were reduced by the 5-HT(2A/2C) receptor antagonist ketanserin (3 x 10(-8) mol/l). Src is one candidate for 5-HT-stimulated CAS tyrosyl-phosphorylation as 5-HT promoted interaction of Src and CAS in coimmunoprecipitation experiments, and the Src tyrosine kinase inhibitor PP1 (10(-5) mol/l) abolished 5-HT-induced tyrosyl-phosphorylation of CAS and reduced 5-HT- and alpha-methyl-5-HT-induced contraction. Antisense oligodeoxynucleotides delivered to the aorta reduced CAS expression (33% control) and arterial contraction to alpha-methyl-5-HT (45% of control), independent of changes in myosin light chain phosphorylation. These data are the first to implicate CAS in the signal transduction of 5-HT.