Anxiety-like Behavior in C57BL/6J and DBA/2J Mice: Pharmacological Characterization of the Elevated Zero Maze and the Influence of Age-related Differences on Behavior

Anxiety disorders affect a significant proportion of the population and can be debilitating in some circumstances. The exact etiology of these disorders remains to be determined and animal models are an important part of that effort. The elevated zero maze, a behavioral measure of anxiety, was introduced as an alternative to the popular elevated plus maze. While the elevated zero maze has been pharmacologically validated in rats, the available data in mice is more limited. Similarly, the data available on anxiety-like behavior in adolescent mice lacks breadth despite considerable evidence suggesting that developmental processes during this period play a role in the etiology of anxiety disorders. In order to extend the available pharmacological data on the elevated zero maze and clarify age-related differences in anxiety-like behavior, three experiments using C57BL/6J and DBA/2J mice were performed. Experiments 1 and 2 examined the effects of chlordiazepoxide and a serotonin norepinephrine reuptake inhibitor on anxiety-like behavior in these strains. Experiment 3 examined age-related differences between these strains in anxiety-like behavior during periadolescence, adolescence, and late adolescence. Anxiety-like behavior was found to vary with strain, task, drug, and age. These data extend our knowledge of basline behavior in these strains and extend the foundation upon which to understand the etiology and treatment of anxiety disorders

Feasibility and Acceptability of the Modified Antiretroviral Treatment Access Study (MARTAS) Intervention Based on a Pilot Study in Ukraine.

We conducted a pilot of the Modified Antiretroviral Treatment Access Study (MARTAS), a linkage to HIV treatment intervention, prior to implementing a multisite randomized controlled trial (RCT) in Ukraine. The objectives of the pilot were to assess the feasibility and acceptability of the MARTAS intervention among a small sample of adults recently diagnosed with HIV at specialty clinics in the Mykolaiv region of Ukraine in 2015. The adapted intervention consisted of up to 6 individual-level sessions with a linkage coordinator (nurse) over a 90-day period. Overall, 22 persons participated in the pilot. On average, participants received 4.2 sessions and 14 participants linked to HIV care within 3 months of study enrollment. All 18 participants who completed the acceptability survey expressed high satisfaction with their interaction with their linkage coordinator. The results of the pilot demonstrated feasibility and acceptability of the MARTAS intervention in advance of a larger scale RCT in Ukraine

Patient and provider perspectives inform an intervention to improve linkage to care for HIV patients in Ukraine.

BACKGROUND:Engagement with HIV medical care is critical to successful HIV treatment and prevention efforts. However, in Ukraine, delays in the timely initiation of HIV treatment hamper viral suppression. By January 01, 2016, only 126,604 (57.5%) of the estimated 220,000 people living with HIV (PLWH) had registered for HIV care, and most (55.1%) of those who registered for HIV care in 2015 did that at a late stage of infection. In the US, Anti-Retroviral Treatment and Access to Services (ARTAS) intervention successfully linked newly diagnosed PLWH to HIV services using strengths-based case management with a linkage coordinator. To tailor the ARTAS intervention for Ukraine, we conducted a qualitative study with patients and providers to understand barriers and facilitators that influence linkage to HIV care. METHODS:During September-October 2014, we conducted 20 in-depth interviews with HIV-positive patients and two focus groups with physicians in infectious disease, sexually transmitted infection (STI), and addiction clinics in Dnipropetrovsk Region of Ukraine. Interviews and focus groups were audio-recorded and transcribed verbatim. We translated illustrative quotes into English. We used thematic analysis for the data analysis. RESULTS:Participants (20 patients and 14 physicians) identified multiple, mostly individual-level factors influencing HIV care initiation. Key barriers included lack of HIV knowledge, non-acceptance of HIV diagnosis, fear of HIV disclosure, lack of psychological support from health providers, and HIV stigma in community. Responsibility for one's health, health deterioration, and supportive provider communication were reported as facilitators to linkage to care. Expected benefits from the case management intervention included psychological support, HIV education, and help with navigating the segmented health system. CONCLUSIONS:The findings from the study will be used to optimize the ARTAS for the Ukrainian context. Our findings can also support future linkage-to-care strategies in other countries of Eastern Europe and Central Asia

Potential Cost Savings of Not Doing CD4 Counts in HIV Positive People In Rhode Island With An Undetectable Viral Load

CD4 cells fight infections in the body. When someone contacts Human Immunodeficiency Virus (HIV), their CD4 cells are taken over by HIV which turns them into manufacturers of many copies of the virus. The Viral Load (VL) measures the amount of virus in the blood. When HIV takes over the CD4 cells, the VL increases while the number of necessary CD4 cells decreases. When patients maintain stable treatment, their CD4 counts rise, and VLs may become undetectable, indicating the virus is too little to be detected in their blood. Knowing this, is frequent CD4 counts necessary for those with undetectable viral loads? We hypothesized that a lot of money can be saved by not performing CD4 counts in HIV patients that have undetectable VLs. In Rhode Island, of the 2,000-3,000 people with HIV/AIDS, 1,500-2,000 are being treated. About 69% (average: 1,208) have undetectable VLs. Health organizations recommend CD4 counts be administered every 3-6 months. With the cost of CD4 tests averaging $53, the frequency of testing can be costly. If undetectable patients get tested quarterly, the average cost would be$256,096. If tested every 6 months, the average cost would be $128,048. Based on these calculations, if these tests were eliminated, Rhode Island could save substantial amounts of money over time. Eliminating tests for undetectable patients (abiding by the recommended 6 month checkup) would save an average of$128,048 annually, an average of $640,240 over 5 years, and an average of$1,280,480 over 10 years

HIV Suppression among Patients on Treatment in Vietnam: A Review of HIV Viral Load Testing in a Public Urban Clinic in Ho Chi Minh City

Background. There are few reports of HIV viral load (VL) testing among patients on ART in Vietnam. Methods. From a public clinic in Ho Chi Minh City (HCMC), we reviewed cases of VL measurements from adults on ART. Results. We identified 228 cases. Median age was 30 years (27–34), 85% were male, and 77% had a history of IDU. The mean ART duration was 26 months (95% CI 25–27); d4T/3TC/NVP was the most common regimen. Viral suppression was seen in 160/228 (70%). Viremia (>1000 copies/mL) was associated with prior ART exposure (OR 5.68, P < .0001) and immunologic failure (OR 4.69, P = .0001). Targeted testing accounted for 13% of cases, only half of which yielded viremia. Conclusion. We demonstrate a high HIV suppression rate among patients on ART in HCMC, Vietnam. In this setting, routine testing detects viremia missed by targeted testing

Delayed entry to care by men with HIV infection in Kumasi, Ghana

Introduction: In resource-limited settings, men may face considerable barriers to accessing HIV care as early interventions tend to focus on antenatal care settings.Methods: We performed a retrospective chart review of all adult patients referred to Komfo Anokye Teaching Hospital HIV clinic in Kumasi, Ghana in 2011 to identify the differences in clinical and  demographic variables by gender at presentation to care using two-sample t tests with adjusted variance and Wilcox rank sum tests for continuous variables and Pearson chi-squared tests for categorical  variables. We also compared differences in clinical and  demographic variables among men stratified by CD4 count at initiation of care in order to identify  variables associated with later entry to care. Results: Demographically, men were more likely to be older  (men age 42 vs. 37, p&lt;0.01), have a  greater number of dependent children (1.8 v. 1.5, p=0.04), to be living with or married to their partner (65.4% vs. 49.0%, p&lt;0.01), and to have a higher level of education (tertiary education, 45.8% vs. 25.4%, p&lt;0.01) than women. Clinically, men were more likely to have a lower CD4 count at entry to care (260 v. 311 cells/μL, p&lt;0.01), to report clinical symptoms to the nurse during intake (p&lt;0.01), and to have any history of alcohol use (p&lt;0.01). Conclusion: Men in Ghana are accessing treatment at a later stage of their disease than women. Efforts to test and link men to care early should be intensified.Key words: Gender disparities, men, HIV, Ghana, access to care, entry to care

HIV-2 diagnosis and quantification in high-risk patients

Current diagnostic assays for HIV-1 do not always test for the presence of HIV-2 in the United States. We present the case of a patient from Cape Verde, who was admitted to our hospital with rapidly deteriorating neurological function and multiple white matter lesions on MRI likely secondary to progressive multifocal leukoencephalopathy (PML). Initially, the patient had a positive EIA for HIV, but a negative HIV-1 Western Blot and no viral load detected on a branched-DNA assay. A repeat viral load by reverse transcriptase methodology (RT-DNA) detected 121,000 copies and an HIV-2 Western Blot was positive. The case highlights an extremely rare presentation of HIV-2 with severe neurological disease. We discuss the different tests available for the diagnosis and monitoring of HIV-2 in the United States

Patients\u27 perspectives of tuberculosis treatment challenges and barriers to treatment adherence in Ukraine: a qualitative study

OBJECTIVES: To understand the challenges faced by patients with tuberculosis (TB) and factors that influence TB treatment adherence in Ukraine. DESIGN: Qualitative study. SETTING: TB treatment facilities in Kyiv Oblast, Ukraine. PARTICIPANTS: Sixty adults who had undergone treatment for drug-sensitive TB between June 2012 and August 2015. METHODS: We conducted semistructured, in-depth, individual interviews among a purposively selected clinical sample of patients previously treated for drug-sensitive TB. Interview content encompassed WHO\u27s framework for barriers to adherence to long-term therapies and included questions about patient preferences and motivators concerning treatment adherence. We examined treatment experience across strata defined by previously identified risk correlates of non-adherence. RESULTS: Among 60 participants, 19 (32.8%) were HIV positive, 12 (20.3%) had substance use disorder and 9 (15.0%) had not completed TB treatment. Respondents discussed the psychological distress associated with hospital-based TB care, as well as perceived unsupportive, antagonistic interactions with TB providers as major challenges to treatment adherence. An additional barrier to successful treatment completion included the financial toll of lost income during TB treatment, which was exacerbated by the additional costs of ancillary medications and transportation to ambulatory TB clinics. The high pill burden of TB treatment also undermined adherence. These challenges were endorsed among participants with and without major risk factors for non-adherence. CONCLUSIONS: Our findings highlight important barriers to TB treatment adherence in this study population and suggest specific interventions that may be beneficial in mitigating high rates of poor treatment outcomes for TB in Ukraine

Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

SummaryBackgroundHematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease.MethodsThis study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition.ResultsThe frequencies of neutropenia (absolute neutrophil count ≤1.3×109/l), anemia (hemoglobin ≤10g/dl), and thrombocytopenia (platelets ≤125×109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p<0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection.ConclusionsDifferences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings

Clinical Impact and Cost-Effectiveness of Expanded Voluntary HIV Testing in India

Background: Despite expanding access to antiretroviral therapy (ART), most of the estimated 2.3 to 2.5 million HIV-infected individuals in India remain undiagnosed. The questions of whom to test for HIV and at what frequency remain unclear. Methods: We used a simulation model of HIV testing and treatment to examine alternative HIV screening strategies: 1) current practice, 2) one-time, 3) every five years, and 4) annually; and we applied these strategies to three population scenarios: 1) the general Indian population (“national population”), i.e. base case (HIV prevalence 0.29%; incidence 0.032/100 person-years [PY]); 2) high-prevalence districts (HIV prevalence 0.8%; incidence 0.088/100 PY), and 3) high-risk groups (HIV prevalence 5.0%; incidence 0.552/100 PY). Cohort characteristics reflected Indians reporting for HIV testing, with a median age of 35 years, 66% men, and a mean CD4 count of 305 cells/µl. The cost of a rapid HIV test was $3.33. Outcomes included life expectancy, HIV-related direct medical costs, incremental cost-effectiveness ratios (ICERs), and secondary transmission benefits. The threshold for “cost-effective” was defined as 3x the annual per capita GDP of India ($3,900/year of life saved [YLS]), or for “very cost-effective” was <1x the annual per capita GDP ($1,300/YLS). Results: Compared to current practice, one-time screening was very cost-effective in the national population (ICER:$1,100/YLS), high-prevalence districts (ICER: $800/YLS), and high-risk groups (ICER:$800/YLS). Screening every five years in the national population (ICER: $1,900/YLS) and annual screening in high-prevalence districts (ICER:$1,900/YLS) and high-risk groups (ICER: $1,800/YLS) were also cost-effective. Results were most sensitive to costs of care and linkage-to-care. Conclusions: In India, voluntary HIV screening of the national population every five years offers substantial clinical benefit and is cost-effective. Annual screening is cost-effective among high-risk groups and in high-prevalence districts nationally. Routine HIV screening in India should be implemented