Daniel E. Gordon

Changes in whole tissue biosynthesis of γ-amino butyric acid (GABA) in basal ganglia of the dystonia (dtAlb) mouse

Abstract The mouse mutant dystonia musculorum shows many of the symptoms of of human dystonics. In this study whole tissue samples of mutant striatum and substantia nigra showed almost 50% less γ-amino butyric acid (GABA) biosynthetic capacity than controls of the same inbred strain. Hypothalamic values were unchanged. The defect appears to be one of substrate localization, since both crude extract enzyme activity and the fractional conversion of glutamate to GABA were unaffected by the mutation. When tissue is disrupted, high-affinity synaptosomal uptake to glutamate does not appear to be affected; therefore an endogenous inhibitor of glutamate transport is postulated for the mutant.

Transmitted Antiretroviral Drug Resistance in New York State, 2006-2008: Results from a New Surveillance System

Background HIV transmitted drug resistance (TDR) is a public health concern because it has the potential to compromise antiretroviral therapy (ART) at the population level. In New York State, high prevalence of TDR in a local cohort and a multiclass resistant case cluster led to the development and implementation of a statewide resistance surveillance system. Methodology We conducted a cross-sectional analysis of the 13,109 cases of HIV infection that were newly diagnosed and reported in New York State between 2006 and 2008, including 4,155 with HIV genotypes drawn within 3 months of initial diagnosis and electronically reported to the new resistance surveillance system. We assessed compliance with DHHS recommendations for genotypic resistance testing and estimated TDR among new HIV diagnoses. Principal Findings Of 13,109 new HIV diagnoses, 9,785 (75%) had laboratory evidence of utilization of HIV-related medical care, and 4,155 (43%) had a genotype performed within 3 months of initial diagnosis. Of these, 11.2% (95% confidence interval [CI], 10.2%–12.1%) had any evidence of TDR. The proportion with mutations associated with any antiretroviral agent in the NNRTI, NRTI or PI class was 6.3% (5.5%–7.0%), 4.3% (3.6%–4.9%) and 2.9% (2.4%–3.4%), respectively. Multiclass resistance was observed in <1%. TDR did not increase significantly over time (p for trend = 0.204). Men who have sex with men were not more likely to have TDR than persons with heterosexual risk factor (OR 1.0 (0.77–1.30)). TDR to EFV+TDF+FTC and LPV/r+TDF+FTC regimens was 7.1% (6.3%–7.9%) and 1.4% (1.0%–1.8%), respectively. Conclusions/Significance TDR appears to be evenly distributed and stable among new HIV diagnoses in New York State; multiclass TDR is rare. Less than half of new diagnoses initiating care received a genotype per DHHS guidelines.

Postpartum Human Immunodeficiency Virus Care Among Women Diagnosed During Pregnancy.

OBJECTIVE: To identify factors associated with continuity of care and human immunodeficiency virus (HIV) virologic suppression among postpartum women diagnosed with HIV during pregnancy in New York State. METHODS: This retrospective cohort study was conducted among 228 HIV-infected women diagnosed during pregnancy between 2008 and 2010. Initial receipt of HIV-related medical care (first CD4 or viral load test after diagnosis) was evaluated at 30 days after diagnosis and before delivery. Retention in care (2 or more CD4 or viral load tests, 90 days or greater apart) and virologic suppression (viral load 200 copies/mL or less) were evaluated in the 12 months after hospital discharge. RESULTS: Most women had their initial HIV-related care encounter within 30 days of diagnosis (74%) and before delivery (87%). Of these women, 70% were retained in the first year postpartum. Women waiting more than 30 days for their initial HIV-related care encounter were more likely diagnosed in the first (29%) compared with the third (11%) trimester and were of younger (younger than 25 years, 32%) compared with older (35 years or older, 13%) age. Loss to follow-up within the first year was significantly greater among women diagnosed in the third compared with the first trimester (adjusted relative risk 2.21, 95% confidence interval [CI] 1.41–3.45) and among women who had a cesarean compared with vaginal delivery (adjusted relative risk 1.76, 95% CI 1.07–2.91). Of the 178 women with one or more HIV viral load test in the first year postpartum, 58% had an unsuppressed viral load. CONCLUSION: Despite the high proportion retained in care, many women had poor postpartum virologic control. Robust strategies are needed to increase virologic suppression among newly diagnosed postpartum HIV-infected women.

Mandating the offer of HIV testing in New York: simulating the epidemic impact and resource needs.

Background:A 2010 New York law requires that patients aged 13–64 years be offered HIV testing in routine medical care settings. Past studies report the clinical outcomes, cost-effectiveness, and budget impact of expanded HIV testing nationally and within clinics but have not examined how state policies affect resource needs and epidemic outcomes. Methods:A system dynamics model of HIV testing and care was developed, where disease progression and transmission differ by awareness of HIV status, engagement in care, and disease stage. Data sources include HIV surveillance, Medicaid claims, and literature. The model projected how alternate implementation scenarios would change new infections, diagnoses, linkage to care, and living HIV cases over 10 years. Results:Without the law, the model projects declining new infections, newly diagnosed cases, individuals newly linked to care, and fraction of undiagnosed cases (reductions of 62.8%, 59.7%, 54.1%, and 57.8%) and a slight increase in living diagnosed cases and individuals in care (2.2% and 6.1%). The law will further reduce new infections, diagnosed AIDS cases, and the fraction undiagnosed and initially increase and then decrease newly diagnosed cases. Outcomes were consistent across scenarios with different testing offer frequencies and implementation times but differed according to the level of implementation. Conclusions:A mandatory offer of HIV testing may increase diagnoses and avert infections but will not eliminate the epidemic. Despite declines in new infections, previously diagnosed cases will continue to need access to antiretroviral therapy, highlighting the importance of continued funding for HIV care.

Timing of entry to care by newly diagnosed HIV cases before and after the 2010 New York State HIV testing law.

Abstract:Prompt entry to care after HIV diagnosis benefits the infected individual and reduces the likelihood of further transmission of the virus. The New York State HIV Testing Law of 2010 requires diagnosing providers to refer persons newly diagnosed with HIV to follow-up medical care. This study used routinely collected HIV-related laboratory data from the New York State HIV surveillance system to assess whether the fraction of newly diagnosed cases entering care within 90 days of diagnosis increased after the implementation of the law. Laboratory data on 23,302 newly diagnosed cases showed that entry to care within 90 days rose steadily from 72.0% in 2007 to 85.4% in 2012. The rise was observed across all race/ethnic groups, ages, transmission risk groups, sexes, and regions of residence. Logistic regression analyses of entry to care pre-law and post-law, controlling for demographic characteristics, transmission risk, and geographic area, indicate that percentage of newly diagnosed cases entering care within 90 days grew more rapidly in the post-law period. This is consistent with a positive effect of the law on entry to care.

An End-User Participatory Approach to Collaboratively Refine HIV Care Data, The New York State Experience

Existing data dissemination structures primarily rely on top-down approaches. Unless designed with the end user in mind, this may impair data-driven clinical improvements to Human Immunodeficiency Virus (HIV) prevention and care. In this study, we implemented a data visualization activity to create region-specific data presentations collaboratively with HIV providers, consumers of HIV care, and New York State (NYS) Department of Health AIDS Institute staff for use in local HIV care decision-making. Data from the NYS HIV Surveillance Registry (2009–2013) and HIV care facilities (2010–2015) participating in a Health Resources and Services Administration (HRSA) Systems Linkages and Access to Care project were used. Each data package incorporated visuals for: linkage to HIV care, retention in care and HIV viral suppression. End-users were vocal about their data needs and their capacity to interpret public health data. This experience suggests that data dissemination strategies should incorporate input from the end user to improve comprehension and optimize HIV care.

Modeling the Declining Positivity Rates for Human Immunodeficiency Virus Testing in New York State.

OBJECTIVE New York health care providers have experienced declining percentages of positive human immunodeficiency virus (HIV) tests among patients. Furthermore, observed positivity rates are lower than expected on the basis of the national estimate that one-fifth of HIV-infected residents are unaware of their infection. We used mathematical modeling to evaluate whether this decline could be a result of declining numbers of HIV-infected persons who are unaware of their infection, a measure that is impossible to measure directly. DESIGN AND SETTING A stock-and-flow mathematical model of HIV incidence, testing, and diagnosis was developed. The model includes stocks for uninfected, infected and unaware (in 4 disease stages), and diagnosed individuals. Inputs came from published literature and time series (2006-2009) for estimated new infections, newly diagnosed HIV cases, living diagnosed cases, mortality, and diagnosis rates in New York. MAIN OUTCOME MEASURES Primary model outcomes were the percentage of HIV-infected persons unaware of their infection and the percentage of HIV tests with a positive result (HIV positivity rate). RESULTS In the base case, the estimated percentage of unaware HIV-infected persons declined from 14.2% in 2006 (range, 11.9%-16.5%) to 11.8% in 2010 (range, 9.9%-13.1%). The HIV positivity rate, assuming testing occurred independent of risk, was 0.12% in 2006 (range, 0.11%-0.15%) and 0.11% in 2010 (range, 0.10%-0.13%). The observed HIV positivity rate was more than 4 times the expected positivity rate based on the model. CONCLUSIONS HIV test positivity is a readily available indicator, but it cannot distinguish causes of underlying changes. Findings suggest that the percentage of unaware HIV-infected New Yorkers is lower than the national estimate and that the observed HIV test positivity rate is greater than expected if infected and uninfected individuals tested at the same rate, indicating that testing efforts are appropriately targeting undiagnosed cases.