Annual and durable HIV retention in care and viral suppression among patients of Peter Ho Clinic, 2013-2017.

OBJECTIVES: To determine rates of annual and durable retention in medical care and viral suppression among patients enrolled in the Peter Ho Clinic, from 2013-2017. METHODS: This is a retrospective review of medical record data in an urban clinic, located in Newark, New Jersey, a high prevalence area of persons living with HIV. Viral load data were electronically downloaded, in rolling 1-year intervals, in two-month increments, from January 1, 2013 to December 31, 2019. Three teams were established, and every two months, they were provided with an updated list of patients with virologic failure. Retention and viral suppression rates were first calculated for each calendar-year. After patients were determined to be retained/suppressed annually, the proportion of patients with durable retention and viral suppression were calculated in two, three, four, five and six-year periods. Descriptive statistics were used to summarize sample characteristics by retention in care, virologic failure and viral suppression with Pearson Chi-square; p-value <0.05 was statistically significant. Multiple logistic regression models identified patient characteristics associated with retention in medical care, virologic failure and suppression. RESULTS: As of December 31, 2017, 1000 (57%) patients were retained in medical care of whom 870 (87%) were suppressed. Between 2013 and 2016, decreases in annual (85% to 77%) and durable retention in care were noted: two-year (72% to 70%) and three-year (63% to 59%) periods. However, increases were noted for 2017, in annual (89%) and durable retention in the two-year period (79%). In the adjusted model, when compared to current patients, retention in care was less likely among patients reengaging in medical care (adjusted Odds Ratio (aOR): 0.77, 95% CI: 0.61-0.98) but more likely among those newly diagnosed from 2014-2017 (aOR: 1.57, 95% CI: 1.08-2.29), compared to those in care since 2013. A higher proportion of patients re-engaging in medical care had virologic failure than current patients (56% vs. 47%, p < 0.0001). As age decreased, virologic failure was more likely (p<0.0001). Between 2013 and 2017, increases in annual (74% to 87%) and durable viral suppression were noted: two-year (59% to 73%) and three-year (49% to 58%) periods. Viral suppression was more likely among patients retained in medical care up to 2017 versus those who were not (aOR: 5.52, 95% CI: 4.08-7.46). Those less likely to be suppressed were 20-29 vs. 60 years or older (aOR: 0.52, 95% CI: 0.28-0.97), had public vs. private insurance (aOR: 0.29, 95% CI: 0.15-0.55) and public vs. private housing (aOR: 0.59, 95% CI: 0.40-0.87). CONCLUSIONS: Restructuring clinical services at this urban clinic was associated with improved viral suppression. However, concurrent interventions to ensure retention in medical care were not implemented. Both retention in care and viral suppression interventions should be implemented in tandem to achieve an end to the epidemic. Retention in care and viral suppression should be measured longitudinally, instead of cross-sectional yearly evaluations, to capture dynamic changes in these indicators.

Rapid Testing Algorithm Performance in a Low-Prevalence Environment.

BACKGROUND: The performance of a statewide HIV rapid test algorithm (RTA) in a low-prevalence setting (0.71%) was examined for 3 years. METHODS: An initial rapid screening by HIV-1/2 Ag/Ab Combo test (RT#1) with Ab verification using a second, different rapid test (RT#2) was conducted. Clinic referral was immediate for antigen-only-positive screens. Antibody-positive screens were confirmed by RT#2. Specimens were collected following discordant RTA results (initially Ab-POS by RT#1, but negative on RT#2) and tested in accordance with the current Centers for Disease Control and Prevention/Association of Public Health Laboratories-based HIV diagnostic algorithm supplemented by a quantitative viral load whenever possible. RESULTS: Of 310,785 tests performed, 2400 preliminary positive screens were identified; 2191 (91.8%) confirmed by RT#2. Of 13 Determine Combo AG-POS results identified, only 1 confirmed positive. Of the remaining 196 discordant results, 182 (92.9%) were uninfected, including 13 with AG-POS/AB-POS results. Of 14 true positives (7.1%) identified after discordant RTA results, the average quantitative HIV-1 viral load was 277,385 copies/mL, but 5 (35.7%) of 14 had viral loads <1000 copies/mL. Among the 2191 "presumptive positive" by RTA, 3 false-positive (FP) RTAs were reported (both rapid tests having positive results, while the HIV-1/2 Ag/Ab assay and quantitative HIV-1 viral load showed negative results). CONCLUSIONS: The RTA was effective in predicting true-positive HIV test results and facilitating linkage to care. Discordant results were infrequent. Fingerstick DC Ag detection identified a single early infection. Many discordant cases that were subsequently positive were associated with viral loads <1000 copies/mL.

Same-Day Medical Visit Increases Viral Suppression, Peter Ho Memorial Clinic, 2014-2015 and 2016-2017.

Viral suppression (VS) in patients newly diagnosed with HIV is critical to reducing morbidity, mortality, and new transmissions. Rapid initiation of antiretroviral therapy (ART) is a promising model to improve VS, but patients must be seen expeditiously by a prescribing provider. Our retrospective study compared patients achieving VS after introduction of medical visits on the same day as HIV diagnoses from 2014 to 2017. The time to VS was evaluated using survival analysis. Wilcoxon two-sample tests evaluated median times to VS (after diagnosis and ART receipt). When 2016-2017 was compared with 2014-2015, a higher proportion of patients achieved VS (96% and 90%, respectively; p = .0292); the median time to VS decreased to 88 from 101 days after diagnosis and to 44 from 70 days after receipt of ART. As clinicians consider rapid ART initiation, a medical visit on the same day as HIV diagnosis is an intermediate intervention that may improve VS.

Effect of a Rapid Test Algorithm on Linkage to Medical Care and Viral Suppression Among New Jersey Residents, 2007 to 2015.

BACKGROUND: Efforts to identify and link human immunodeficiency virus-infected persons to medical care are the first steps to achieving viral suppression. In the United States, the goals are to link 85% of newly diagnosed persons to medical care in 30 days or less and for 80% to become virally suppressed by 2020. Among newly diagnosed residents from 2007 to 2015, in New Jersey, we evaluated the impact of a rapid testing algorithm (RTA) on linkage to medical care and viral suppression. METHODS: This is a retrospective review of data from New Jersey's Enhanced HIV/AIDS Reporting System for residents, newly diagnosed at 13 years or older, from 2007 to 2015. We used survival analysis methods to estimate the proportion of residents and time to linkage to medical care and viral suppression. RESULTS: Of 8508 newly diagnosed residents, 60.3% and 72.3% were linked to medical care in 30 days or less and 90 days or less, respectively; 45.7% achieved viral suppression in 365 days or less. Linkage to medical care in 90 days or less and viral suppression in 365 days or less were more likely among those tested by RTA than laboratory testing. The adjusted hazard ratios for linkage to medical care, in clinical sites were 1.41, (95% confidence interval [CI], 1.22-1.63 and 1.08, 95% CI, 0.97-1.2 in community sites. The adjusted hazard ratios for viral suppression in clinical sites were 1.25 (95% CI, 1.05-1.47 and 1.16, 95% CI, 1.01-1.32, in community sites. CONCLUSIONS: Implementation of a RTA may eliminate barriers to linkage to medical care and viral suppression leading to decreased morbidity, mortality, and transmission.

An anonymous unlinked sero-prevalence survey of HIVHCV in an urban Emergency Department.

BACKGROUND: In 2002, the sero-prevalence of human immunodeficiency virus-1 (HIV) in the Emergency Department (ED), University Hospital, Newark, New Jersey was 10.4%. Both HIV and hepatitis C virus (HCV) are transmitted by injection drug use (IDU) or sexual contact. However, the degree of concurrent positive HCV antibody status in HIV-infected ED patients is unknown. OBJECTIVES: In this study we determined the sero-prevalence of HIV and HIVHCV in HIV-positive patients in the ED. STUDY DESIGN: A cross-sectional study using an anonymous sero-prevalence survey was conducted from 7/1/2008 to 8/23/2008. Medical records were reviewed and de-identified; remnant blood specimens were also de-identified and tested for HIV antibody, and if positive, HCV antibody. RESULTS: Of 3488 specimens, 225 (6.5%, 95% CI: 5.7-7.3%) were positive for HIV antibody. Seventy-four patients 74/225 (32.9%, 95% CI: 33.8-46.5%) were unaware of their sero-positivity. Forty percent of HIV positive patients (90/225, 95% CI: 33.8-46.5%) were HCV antibody positive. The highest seroprevalence of HIVHCV antibody was among older patients (≥ 45 years), and patients with positive urine toxicology and elevated liver function tests. DISCUSSION: Given the high prevalence of HIV and HIVHCV antibody in the ED, routine testing is important for patients ≥ 45 years with positive urine toxicology and elevated liver function tests.

Finding those at risk: acute HIV infection in Newark, NJ.

BACKGROUND: A screening strategy combining rapid HIV-1/2 (HIV) antibody testing with pooled HIV-1 RNA testing increases identification of HIV infections, but may have other limitations that restrict its usefulness to all but the highest incidence populations. OBJECTIVE: By combining rapid antibody detection and pooled nucleic acid amplification testing (NAAT) testing, we sought to improve detection of early HIV-1 infections in an urban Newark, NJ hospital setting. STUDY DESIGN: Pooled NAAT HIV-1 RNA testing was offered to emergency department patients and outpatients being screened for HIV antibodies by fingerstick-rapid HIV testing. For those negative by rapid HIV and agreeing to NAAT testing, pooled plasma samples were prepared and sent to the University of Washington where real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification was performed. RESULTS: Of 13,226 individuals screened, 6381 had rapid antibody testing alone, and 6845 agreed to add NAAT HIV screening. Rapid testing identified 115 antibody positive individuals. Pooled NAAT increased HIV-1 case detection by 7.0% identifying 8 additional cases. Overall, acute HIV infection yield was 0.12%. While males represent only 48.1% of those tested by NAAT, all samples that screened positive for HIV-1 RNA were obtained from men. CONCLUSION: HIV-1 RNA testing of pooled, HIV antibody-negative specimens permits identification of recent infections. In Newark, pooled NAAT increased HIV-1 case detection and provided an opportunity to focus on treatment and prevention messages for those most at risk of transmitting infection. Although constrained by client willingness to participate in testing associated with a need to return to receive further results, use of pooled NAAT improved early infection sensitivity.

Origins of arousal: roles for medullary reticular neurons.

The existence of a primitive CNS function involved in the activation of all vertebrate behaviors, generalized arousal (GA), has been proposed. Here, we provide an overview of the neuroanatomical, neurophysiological and molecular properties of reticular neurons within the nucleus gigantocellularis (NGC) of the mammalian medulla, and propose that the properties of these neurons equip them to contribute powerfully to GA. We also explore the hypothesis that these neurons may have evolved from the Mauthner cell in the medulla of teleost fish, although NGC neurons have a wider range of action far beyond the specific escape network served by Mauthner cells. Understanding the neuronal circuits that control and regulate GA is central to understanding how motivated behaviors such as hunger, thirst and sexual behaviors arise.

Cost effectiveness analysis of the New Jersey rapid testing algorithm for HIV testing in publicly funded testing sites.

BACKGROUND: Before 2009, New Jersey (NJ) publicly funded counseling and testing sites (CTS) tested for HIV using a single rapid test followed, when positive, by a Western Blot (WB) for confirmation. With this strategy, 74.8% of confirmed positive clients returned to receive test results. To improve the client notification rate at these centers, the New Jersey (NJ) Division of HIV, STD and TB Services (DHSTS) implemented a rapid testing algorithm (RTA) which utilizes a second, different, rapid test to verify a preliminary positive. OBJECTIVE: To compare the cost-effectiveness of the two testing algorithms. STUDY DESIGN: This was a retrospective cost-effectiveness analysis. DATA SOURCES: New Jersey HIV Rapid Testing Support Program (NJHIV) records, DHSTS grant documents, counseling time estimates from an online survey of site supervisors. Costs included test kits and personnel costs from month of RTA implementation through 11/30 in 2008 and 2009. The incremental cost of the RTA was calculated per additional percent of positive clients who were notified and per day earlier notification. RESULTS: In 2008, 215 of 247 clients with a positive rapid HIV test were confirmed positive by WB. 90.9% of clients were notified a mean of 11.4 days after their initial test. 12 refused confirmatory WB. In 2009, 152 of 170 clients with one positive rapid test had a confirmatory second positive rapid test and were notified on the same day. The incremental cost of the RTA was $20.31 per additional positive person notified and $24.31 per day earlier notification or $3.23 per additional positive person and $3.87 per day earlier notification if the WB were eliminated. CONCLUSIONS: The RTA is a cost-effective strategy achieving 100% notification of newly HIV positive clients a mean of 11.4 days earlier compared to standard testing.

Use of a rapid HIV testing algorithm to improve linkage to care.

BACKGROUND: Awaiting definitive diagnosis before scheduling healthcare visits complicates HIV screening and referral. Clients screened by rapid tests as initially reactive often fail to return to receive definitive test results, are not linked to care and enter care late or not at all. OBJECTIVES: To evaluate statewide, (1) the accuracy of a single-visit, two test HIV rapid testing algorithm (RTA) and (2) its effect on referral to care for positive clients. STUDY DESIGN: A two-test RTA was implemented at 24 sites in New Jersey beginning in December 2008. All clients with a reactive rapid HIV test were offered a second rapid HIV test, and RTA results were compared with Western blot (WB). Referral to care occurred based upon two sequential positive rapid tests. RESULTS: The RTA program has screened 51,413 individuals obtaining 426 reactive rapid test results; 394 (92.5%) were reactive by a second rapid test, 32 (7.5%) had a negative second rapid test. Twenty-eight individuals refused WB testing. Of 369 RTA-positive individuals who have WB results, 368 (99.5%) were confirmed positive. Of RTA-positive clients, 290 (73.6%), including 25 (6.6%) who refused Western blot, were immediately referred for care including one individual with a false-positive RTA. CONCLUSIONS: The RTA reduced false positive results by 6.2% and agreed with WB results 99.5% of the time. Improved referral to care compared to traditional rapid HIV screening occurs when immediate referral is based on RTA verification of a preliminary positive rapid test. WB confirmation is not essential for effective screening and contributes to difficulties linking individuals to care.

Distribution of estrogen receptor ß containing cells in the brains of bacterial artificial chromosome transgenic mice.

In the brain, estrogen receptor beta (ERbeta) plays important roles in autonomic functions, stress reactivity and learning and memory processes. However, understanding the function of ERbeta has been restricted by the limited availability of specific antisera, by difficulties discriminating the discrete localization of ERbeta-immunoreactivity (ir) at the light microscopic level in many brain regions and the identification of ERbeta-containing neurons in neurophysiological and molecular studies. Here, we demonstrate that a Esr2 bacterial artificial chromosome (BAC) transgenic mouse line that expresses ERbeta identified by enhanced green fluorescent protein (EGFP) overcomes these shortcomings. Throughout the brain, ERbeta-EGFP was detected in the nuclei and cytoplasm of cells, the majority of which resembled neurons. EGFP often extended into dendritic processes and could be identified either natively or following intensification of EGFP using immunolabeling. The distribution of ERbeta-EGFP cells in brain closely corresponded to that reported for ERbeta protein and mRNA. In particular, ERbeta-EGFP cells were found in autonomic brain regions (i.e., hypothalamic paraventricular nucleus, rostral ventrolateral medulla and nucleus of the solitary tract), in regions associated with anxiety and stress behaviors (i.e., bed nucleus of the stria terminalis, amygdala, periaqueductal gray, raphe and parabrachial nuclei) and in regions involved in learning and memory processes (i.e., basal forebrain, cerebral cortex and hippocampus). Additionally, dual label light and electron microscopic studies in select brain areas demonstrate that cell containing ERbeta-EGFP colocalize with both nuclear and extranuclear ERbeta-immunoreactivity. These findings support the utility of Esr2 BAC transgenic reporter mice for future studies understanding the role of ERbeta in CNS function.

Multimodal sensory responses of nucleus reticularis gigantocellularis and the responses' relation to cortical and motor activation.

The connectivity of large neurons of the nucleus reticularis gigantocellularis (NRGc) in the medullary reticular formation potentially allows both for the integration of stimuli, in several modalities, that would demand immediate action, and for coordinated activation of cortical and motoric activity. We have simultaneously recorded cortical local field potentials, neck muscle electromyograph (EMG), and the neural activity of medullary NRGc neurons in unrestrained, unanesthetized rats to determine whether the activity of the NRGc is consistent with the modulation of general arousal. We observed excitatory responses of individual NRGc neurons to all modalities tested: tactile, visual, auditory, vestibular, and olfactory. Excitation was directly linked to increases in neck muscle EMG amplitude and corresponded with increases in the power of fast oscillations (30 to 80 Hz) of cortical activity and decreases in the power of slow oscillations (2 to 8 Hz). Because these reticular formation neurons can respond to broad ranges of stimuli with increased firing rates associated with the initiation of behavioral responses, we infer that they are part of an elementary "first responder" CNS arousal mechanism.

Rapid human immunodeficiency virus test quality assurance practices and outcomes among testing sites affiliated with 17 public health departments.

Rapid human immunodeficiency virus testing is often conducted in nonclinical settings by staff with limited training, so quality assurance (QA) monitoring is critical to ensure accuracy of test results. Rapid tests (n = 86,749) were generally conducted according to manufacturers' instructions, but ongoing testing competency assessments and on-site QA monitoring were not uniformly conducted.

Relations between mechanisms of CNS arousal and mechanisms of stress.

In the centennial year of the birth of Hans Selye, this review compares his classical concepts of stress with a modern approach to mechanisms of CNS arousal. Relations between the two concepts are described. Neuroanatomical, neurophysiological, and functional genomic mechanisms underlying CNS arousal are briefly reviewed. Controls over stress responses and arousal are compared to particular concepts of control system engineering. Understanding these two systems is of crucial importance because their dysregulation is associated with large numbers of disease states.

Effects of Ultraviolet Radiation on the Gram-positive marine bacterium Microbacterium maritypicum.

Although extensive information is available on the effect ultraviolet (UV) radiation has on Gram-negative marine bacteria, there is a scarcity of data concerning UV radiation and Gram-positive marine bacteria. The focus of this paper is on Microbacterium maritypicum, with the Gram-negative Vibrio natriegens being used as a standard of comparison. M. maritypicum exhibited growth over a NaCl range of 0-1000 mM: , with optimum growth occurring between 0 and 400 mM: NaCl. In contrast, V. natriegens grew over a NaCl span of 250-1000 mM: , with best growth being observed between 250 and 600 mM: NaCl. UV radiation experiments were done using the medium with 250 mM: NaCl. For solar (UV-A and B) radiation and log-phase cells, M. maritypicum was determined to be three times more resistant than V. natriegens. For germicidal (UV-C) radiation, the pattern of resistance of the log-phase cells to the lethal effects of the radiation was even more pronounced, with the Gram-positive bacterium being more than 12 to 13 times more resistant. Similar data to the solar and germicidal log-phase UV kill curves were obtained for stationary-phase cells of both organisms. Photoreactivation was observed for both types of cells exposed to UV-C but none for cells treated with UV-A and B. When log phase cells of M.maritypicum were grown at 0.0 and 0.6 M: NaCl and exposed to UV-C radiation, no difference in survivorship patterns was noted from that of 0.25 M: NaCl grown cells. Although this study has only focused on two marine bacteria, our results indicate that the Gram-positive M. maritypicum could have a built-in advantage for survival in some marine ecosystems.

Investigation of false positive results with an oral fluid rapid HIV-1/2 antibody test.

BACKGROUND: In March 2004, the OraQuick rapid HIV antibody test became the first rapid HIV test approved by the US Food and Drug Administration for use on oral fluid specimens. Test results are available in 20 minutes, and the oral fluid test is non-invasive. From August 2004-June 2005, we investigated a sudden increase in false-positive results occurring in a performance study of OraQuick oral-fluid rapid HIV tests in Minnesota. METHODOLOGY/PRINCIPAL FINDINGS: In a field investigation, we reviewed performance study data on oral-fluid and whole-blood OraQuick rapid HIV test device lots and expiration dates and assessed test performance and interpretation with oral-fluid and whole-blood specimens by operators who reported false-positive results. We used multivariate logistic regression to evaluate client demographic and risk characteristics associated with false-positive results. Next, we conducted an incidence study of false-positive OraQuick rapid HIV tests in nine US cities and tested both oral-fluid and finger-stick whole-blood specimens from clients; reactive tests were confirmed with Western blot. Sixteen (4.1%) false-positive oral-fluid results occurred in the performance study from April 15, 2004 through August 31, 2004 with unexpired devices from six test lots among 388 HIV-uninfected clients (specificity, 95.9%; 95% CI: 93.4-97.6). Three test operators who had reported false-positive results performed and interpreted the test according to package-insert instructions. In multivariate analysis, only older age was significantly associated with false-positive results (adjusted odds ratio = 4.5, 95% CI: 1.2-25.7). In the incidence study, all valid oral-fluid and whole-blood results from 2,268 clients were concordant and no false-positive results occurred (100% specificity). CONCLUSIONS/SIGNIFICANCE: The field investigation did not identify a cause for the increase in false-positive oral-fluid results, and the incidence study detected no false-positive results. The findings suggest this was an isolated cluster; the test's overall performance was as specified by the manufacturer.

The effects of salt concentration and growth phase on MRSA solar and germicidal ultraviolet radiation resistance.

The extensive use of antimicrobial drugs has led to the widespread emergence of resistant bacterial strains. One such organism, methicillin-resistant Staphylococcus aureus, is now found extensively in both healthcare facilities and diverse community settings such as households, correctional facilities, and athletic teams. The importance of ultraviolet radiation as an adjunctive therapy to reduce bioburden and improve wound status in patients has been documented. An in vitro study to assess the effects of different types of ultraviolet radiation on antibiotic-resistant strains was conducted to provide information that will aid in the development of rational UV irradiation medical protocols. Methicillin-resistant Staphylococcus aureus was found to be sensitive to both germicidal (ultraviolet C) and solar (ultraviolet A and B) ultraviolet radiation (ultraviolet C substantially more lethal). For both types of ultraviolet radiation, as the medium concentration of sodium chloride increased, the methicillin-resistant Staphylococcus aureus cells exhibited increased sensitivity. It also was shown for both types of ultraviolet radiation that kill curves were comparable for log and stationary phase methicillin-resistant Staphylococcus aureus cells. Photoreactivation was observed for Pseudomonas aeruginosa PAO-1 but not for methicillin-resistant Staphylococcus aureus when ultraviolet C was applied to log phase cells. The Gram-negative Pseudomonas aeruginosa PAO-1 was considerably more sensitive than the Gram-positive methicillin-resistant Staphylococcus aureus to ultraviolet C radiation. The experiments reveal that medium composition exerts a substantial effect on methicillin-resistant Staphylococcus aureus ultraviolet resistance and that this species lacks photoreactivation capacity. This suggests that in a clinical setting, eradication of the bacterium may be achieved at far lower doses of ultraviolet radiation than would be indicated by treatment protocols that do not account for ionic conditions.

Masking and scrambling in the auditory thalamus of awake rats by Gaussian and modulated noises.

This paper provides a look at how modulated broad-band noises modulate the thalamic response evoked by brief probe sounds in the awake animal. We demonstrate that noise not only attenuates the response to probe sounds (masking) but also changes the temporal response pattern (scrambling). Two brief probe sounds, a Gaussian noise burst and a brief sinusoidal tone, were presented in silence and in three ongoing noises. The three noises were targeted at activating the auditory system in qualitatively distinct ways. Dynamic ripple noise, containing many random tone-like elements, is targeted at those parts of the auditory system that respond well to tones. International Collegium of Rehabilitative Audiology noise, comprised of the sum of several simultaneous streams of Schroeder-phase speech, is targeted at those parts of the auditory system that respond well to modulated sounds but lack a well defined response to tones. Gaussian noise is targeted at those parts of the auditory system that respond to acoustic energy regardless of modulation. All noises both attenuated and decreased the precise temporal repeatability of the onset response to probe sounds. In addition, the modulated noises induced context-specific changes in the temporal pattern of the response to probe sounds. Scrambling of the temporal response pattern may be a direct neural correlate of the unfortunate experience of being able to hear, but not understand, speech sounds in noisy environments.