Healthcare Personnel (HCP) Attitudes About Coronavirus Disease 2019 (COVID-19) Vaccination After Emergency Use Authorization.

BACKGROUND: We previously reported on coronavirus disease 2019 (COVID-19) vaccination intent among healthcare personnel (HCP) before emergency use authorization. We found widespread hesitancy and a substantial proportion of HCP did not intend to vaccinate. METHODS: We conducted a cross-sectional survey of HCP, including clinical and nonclinical staff, researchers, and trainees between 21 February and 19 March 2021. The survey evaluated vaccine attitudes, beliefs, intent, and acceptance. RESULTS: Overall, 3981 (87.7%) of respondents had already received a COVID-19 vaccine or planned to get vaccinated. There were significant differences in vaccine acceptance by gender, age, race, and hospital role. Males (93.7%) were more likely than females (89.8%) to report vaccine acceptance (P < .001). Mean age was higher among those reporting vaccine acceptance (P < .001). Physicians and scientists showed the highest acceptance rate (97.3%), whereas staff in ancillary services showed the lowest acceptance rate (79.9%). Unvaccinated respondents were more likely to be females, to have refused vaccines in the past due to reasons other than illness or allergy, to care for COVID-19 patients, or to rely on themselves when making vaccination decision. Vaccine acceptance was more than twice previous intent among Black respondents, an increase from 30.8% to 73.8%, and across all hospital roles with all > 80% vaccine acceptance. CONCLUSIONS: The majority of HCP were vaccinated, much higher than reporting intent before vaccine was available. However, many HCP-particularly ancillary services-are still hesitant. Feasible and effective interventions to address the hesitant, including individually-tailored education strategies are needed, or vaccine can be mandated.

Development of a Telephone-Delivered Acceptance and Commitment Therapy Intervention for People Living with HIV who are Hazardous Drinkers.

Alcohol use among people living with HIV (PWH) has been increasingly recognized as an important component of HIV care. Transdiagnostic treatments, such as Acceptance and Commitment Therapy (ACT), that target core processes common to multiple mental health and substance-related problems, may be ideal in HIV treatment settings where psychological and behavioral health comorbidities are high. In advance of a randomized clinical trial (RCT), the overall objective of this study was to systematically adapt an ACT-based intervention originally developed for smoking cessation, into an ACT intervention for PWH who drink at hazardous levels. Consistent with the ADAPT-ITT model, the adaptation progressed systematically in several phases, which included structured team meetings, three focus group discussions with PWH (N = 13), and in-depth interviews with HIV providers (N = 10), and development of standardized operating procedures for interventionist training, supervision, and eventual RCT implementation. The procedures described here offer a template for transparent reporting on early phase behavioral RCTs.

Ibalizumab, a Novel Monoclonal Antibody for the Management of Multidrug-Resistant HIV-1 Infection.

Limited antiretrovirals are currently available for the management of multidrug-resistant (MDR) HIV-1 infection. Ibalizumab, a recombinant humanized monoclonal antibody, represents the first novel agent for HIV-1 management in over a decade and is the first monoclonal antibody for the treatment of MDR HIV-1 infection in combination with other forms of antiretroviral therapy in heavily treatment-experienced adults who are failing their current antiretroviral regimen. Ibalizumab demonstrates a novel mechanism of action as a CD4-directed postattachment inhibitor and has a favorable pharmacokinetic profile that allows for a dosing interval of every 14 days after an initial loading dose. Clinical studies have demonstrated reasonably substantial antiretroviral activity with ibalizumab among a complex patient population with advanced HIV-1 infection who are receiving an optimized background regimen, where limited therapeutic options exist. Ibalizumab was well tolerated in clinical trials, and the most common adverse effects included diarrhea, nausea, dizziness, fatigue, pyrexia, and rash. Resistance to ibalizumab has also been observed via reduced expression or loss of the potential N-linked glycosylation sites in the V5 loop of the envelope glycoprotein 120. The mechanism of action, pharmacokinetic parameters, efficacy, and safety of ibalizumab present an advance in the management of MDR HIV-1 infection. Future studies and postmarketing experience will further determine longer-term clinical efficacy, safety, and resistance data for ibalizumab.

Test site predicts HIV care linkage and antiretroviral therapy initiation: a prospective 3.5 year cohort study of HIV-positive testers in northern Tanzania.

BACKGROUND: Linkage to HIV care is crucial to the success of antiretroviral therapy (ART) programs worldwide, loss to follow up at all stages of the care continuum is frequent, and long-term prospective studies of care linkage are currently lacking. METHODS: Consecutive clients who tested HIV-positive were enrolled from four HIV testing centers (1 health facility and 3 community-based centers) in the Kilimanjaro region of Tanzania as part of the larger Coping with HIV/AIDS in Tanzania (CHAT) prospective observational study. Biannual interviews were conducted over 3.5 years, assessing care linkage, retention, and mental health. Bivariable and multivariate logistic regression analyses were conducted to determine associations with early death (prior to the second follow up interview) and delayed (>6 months post-test) or failed care linkage. RESULTS: A total of 263 participants were enrolled between November, 2008 and August, 2009 and 240 participants not already linked to care were retained in the final dataset. By 6 months after enrollment, 169 (70.4 %) of 240 participants had presented to an HIV care and treatment facility; 41 (17.1 %) delayed more than 6 months, 15 (6.3 %) died, and 15 (6.3 %) were lost to follow up. Twenty-six patients died before their second follow up visit and were analyzed in the early death group (10.8 %). Just 15 (9.6 %) of those linked to care had started ART within 6 months, but 123 (89.1 %) of patients documented to be ART eligible by local guidelines had started ART by the end of 3.5 years. On multivariate analysis, male gender (OR 1.72; 95 % CI 1.08, 2.75), testing due to illness (OR 1.63; 95 % CI 1.01, 2.63), and higher mean depression scale scores (4 % increased risk per increase in depression score; 95 % CI 1 %, 8 %) were associated with early death. Testing at a community versus a hospital-based site (OR 2.89; 95 % CI 1.79, 4.66) was strongly associated with delaying or never entering care. CONCLUSIONS: Nearly 30 % of the cohort did not have timely care linkage, ART initiation was frequently delayed, and testing at a hospital outpatient department versus community-based testing centers was strongly associated with successful care linkage.

HIV serostatus disclosure in the treatment cascade: evidence from Northern Tanzania.

HIV serostatus disclosure plays an important role in HIV transmission risk reduction and is positively associated with HIV medication adherence and treatment outcomes. However, to date, no study has quantified the role of disclosure across the HIV treatment cascade, particularly in Sub-Saharan Africa. We used data from a cohort of HIV-infected adults in Northern Tanzania to describe associations between disclosure and engagement and retention in the HIV treatment cascade. Between 2008 and 2009, the Coping with HIV/AIDS in Tanzania (CHAT) study enrolled 260 clients newly diagnosed with HIV and 492 HIV-infected patients in established HIV care in two large HIV care and treatment centers in Northern Tanzania. Participants aged 18 and older completed annual clinical assessments and twice-annual in-person interviews for 3.5 years. Using logistic regression models, we assessed sociodemographic correlates of HIV serostatus disclosure to at least one household member, and associations between this disclosure measure and linkage to care, evaluation for antiretroviral therapy (ART) eligibility, ART coverage, and rates of undetectable HIV RNA levels during the follow-up period. Married individuals and those diagnosed earlier were more likely to have disclosed their HIV infection to at least one household member. During follow-up, HIV serostatus disclosure was associated with higher rates of linkage to care, evaluation for ART eligibility, and ART coverage. No significant association was observed with rates of undetectable viral loads. Marginal effects estimates suggest that a 10 percentage-point lower probability of linkage to care for those who did not disclose their HIV serostatus (86% vs. 96%; p = 0.035) was compounded by an 18 percentage-point lower probability of ever receiving a CD4 count (62% vs. 80%; p = .039), and a 20 percentage-point lower probability of ever receiving ART (55% vs. 75%; p = .029). If causal, these findings suggest an important role for disclosure assistance efforts across the HIV treatment cascade.

Treatment retention and care transitions during and after the scale-up of HIV care and treatment in Northern Tanzania.

Decentralization of HIV care is promoted to improve access to antiretroviral therapy in sub-Saharan Africa. This study describes care transitions among HIV-infected persons in Northern Tanzania during a period of rapid decentralization of HIV care and treatment centers (CTCs) from hospitals to local health centers. Between November 2008 and June 2009, 492 HIV-infected patients in established care at two referral hospitals in Moshi, Tanzania, and 262 persons newly diagnosed with HIV were selected for participation in a prospective cohort study entitled Coping with HIV/AIDS in Tanzania. Clinical records and participant self-reports, collected between June and November 2012, were used to describe retention in care and transitions between CTCs during the study period. After a mean follow-up period of 3.5 years, 10% of participants had died, 9% were lost to follow-up, and 11% had moved. Of the remaining participants enrolled from CTCs, more than 90% reported at least one CTC visit during the previous six months, with 98% still in care at the CTC at which they were enrolled. Nearly three out of four newly diagnosed clients listed a referral hospital as their primary CTC. Fewer than 10% of participants ever sought care at another CTC in the study area; nearly 90% of those in care bypassed their closest CTC. Administrative data from all facilities in the study area indicate that new clients, even after the scale-up from 8 CTCs in 2006 to 21 CTCs in 2008, disproportionately selected established CTCs, and client volume at newly approved facilities was highly variable. Despite the decentralization of HIV care and treatment in this setting, many patients continue to bypass their closest CTC to seek care at established facilities. Patient preferences for decentralized HIV care, which may inform optimal resource utilization, are largely unknown and warrant further investigation.

Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up.

BACKGROUND: In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up. METHODS: This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained. RESULTS: 161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01). CONCLUSIONS: After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania.

BACKGROUND: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. METHODS: Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). RESULTS: Seventy participants were randomized to standard (n = 37, 53%) or intensive (n = 33, 47%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04). CONCLUSIONS: Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.

HIV testing preferences in Tanzania: a qualitative exploration of the importance of confidentiality, accessibility, and quality of service.

BACKGROUND: HIV counseling and testing (HCT), an effective preventive strategy and an entry point for care, remains under-utilized in Tanzania. Limited uptake of HCT, despite the widespread availability of varied testing options, suggests that existing options may not align well with population preferences for testing. METHODS: Between October and December 2011, we conducted an exploratory study in the Kilimanjaro Region to develop a conceptual framework for understanding which characteristics of HIV testing are associated with preferences for testing. Forty individuals (55% women, 53% never having tested) participated in in-depth interviews and focus groups to identify factors that influence whether and where people test for HIV. RESULTS: A variety of discrete characteristics of testing venues, test providers, and testing procedures (e.g. distance to testing, counselor experience, type of HIV test, and availability of antiretroviral therapy) mapped conceptually to three domains: confidentiality of testing and test results, quality of HCT, and accessibility and availability of ancillary services. We noted heterogeneous preferences and demonstrate that while some test characteristics overlap and reinforce across multiple domains, others demand clients to make trade-offs between domains. CONCLUSION: Testing decisions appear to be influenced by an array of often inter-linked factors across multiple domains, including quality, confidentiality, and accessibility; perceptions of these factors varied greatly across participants and across available testing options. HCT interventions that jointly target barriers spanning the three domains have the potential to increase uptake of HIV testing and deserve further exploration.

Culturally competent transplant program improves Hispanics' knowledge and attitudes about live kidney donation and transplant.

CONTEXT: Hispanics receive disproportionately fewer live donor kidney transplants than non-Hispanic whites. Increasing Hispanics' knowledge and changing attitudes about live kidney donation may reduce these disparities. OBJECTIVE: To evaluate the effectiveness of culturally and linguistically competent educational sessions delivered through Northwestern University's Hispanic Transplant Program. DESIGN: Baseline and postsession questionnaires were used to evaluate changes in patients' and family members' knowledge and attitudes toward live kidney donation and program satisfaction. Knowledge items related to live kidney donation were scaled, and changes in scores were evaluated via a paired t test. Multiple regression analysis of follow-up knowledge scores controlled for baseline scores was used to estimate the effects of patients' and families' sociodemographic characteristics. Changes in attitude items, including comfort with exploring live kidney donation, were analyzed with χ2 tests. RESULTS: One-hundred thirteen patients and family members completed surveys before and after an education session. Respondents' knowledge about live kidney donation and transplant increased significantly (P<.001) between baseline and after the session. Patients' attitudes toward live kidney donation became more favorable (P< .02), as did family members' attitudes toward being a donor (P < .001) after participating in the program. All respondents reported high levels of satisfaction with the program and preferences for culturally congruent care. CONCLUSIONS: The educational sessions provided by the Hispanic Transplant Program effectively addressed commonly shared Hispanic concerns about live kidney donation. Culturally congruent education increased Hispanic patients' and family members' knowledge and improved attitudes about live donor kidney transplants.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy: An executive summary.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed in the main document.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed.

Comparing actual and perceived causes of fever among community members in a low malaria transmission setting in northern Tanzania.

OBJECTIVE: To compare actual and perceived causes of fever in northern Tanzania. METHODS: In a standardised survey, heads of households in 30 wards in Moshi, Tanzania, were asked to identify the most common cause of fever for children and for adults. Responses were compared to data from a local hospital-based fever aetiology study that used standard diagnostic techniques. RESULTS: Of 810 interviewees, the median (range) age was 48 (16, 102) years and 509 (62.8%) were women. Malaria was the most frequently identified cause of fever, cited by 353 (43.6%) and 459 (56.7%) as the most common cause of fever for children and adults, respectively. In contrast, malaria accounted for 8 (2.0%) of adult and 6 (1.3%) of paediatric febrile admissions in the fever aetiology study. Weather was the second most frequently cited cause of fever. Participants who identified a non-biomedical explanation such as weather as the most common cause of fever were more likely to prefer a traditional healer for treatment of febrile adults (OR 2.7, P < 0.001). Bacterial zoonoses were the most common cause of fever among inpatients, but no interviewees identified infections from animal contact as the most common cause of fever for adults; two (0.2%) identified these infections as the most common cause of fever for children. CONCLUSIONS: Malaria is perceived to be a much more common cause of fever than hospital studies indicate, whereas other important diseases are under-appreciated in northern Tanzania. Belief in non-biomedical explanations of fever is common locally and has important public health consequences.

Quality of neonatal healthcare in Kilimanjaro region, northeast Tanzania: learning from mothers' experiences.

BACKGROUND: With a decline of infant mortality rates, neonatal mortality rates are striking high in development countries particularly sub Saharan Africa. The toolkit for high quality neonatal services describes the principle of patient satisfaction, which we translate as mother's involvement in neonatal care and so better outcomes. The aim of the study was to assess mothers' experiences, perception and satisfaction of neonatal care in the hospitals of Kilimanjaro region of Tanzania. METHODS: A cross sectional study using qualitative and quantitative approaches in 112 semi structured interviews from 14 health facilities. Open ended questions for detection of illness, care given to the baby and time spent by the health worker for care and treatment were studied. Probing of the responses was used to extract and describe findings by a mix of in-depth interview skills. Closed ended questions for the quantitative variables were used to quantify findings for statistical use. Narratives from open ended questions were coded by colours in excel sheet and themes were manually counted. RESULTS: 80 mothers were interviewed from 13 peripheral facilities and 32 mothers were interviewed at a zonal referral hospital of Kilimanjaro region. 59 mothers (73.8%) in the peripheral hospitals of the region noted neonatal problems and they assisted for attaining diagnosis after a showing a concern for a request for further investigations. 11 mothers (13.8%) were able to identify the baby's diagnosis directly without any assistance, followed by 7 mothers (8.7%) who were told by a relative, and 3 mothers (3.7%) who were told of the problem by the doctor that their babies needed medical attention. 24 times mothers in the peripheral hospitals reported bad language like "I don't have time to listen to you every day and every time." 77 mothers in the periphery (90.6%) were not satisfied with the amount of time spent by the doctors in seeing their babies. CONCLUSION: Mothers of the neonates play great roles in identifying the illness of the newborn. Mother's awareness of what might be needed during neonatal support strategies to improve neonatal care in both health facilities and the communities.

Real-world evaluation of linezolid-associated serotonin toxicity with and without concurrent serotonergic agents.

BACKGROUND: The risk of linezolid-associated serotonin toxicity remains unclear. This study sought to evaluate the incidence of serotonin toxicity among hospitalized patients who received linezolid with or without concurrent serotonergic agents (SAs). Secondary outcomes were to assess the dose, agent selection and number of SAs. METHODS: A single-centre, retrospective cohort study of hospitalized patients aged ≥18 years who received at least one dose of linezolid with or without SAs between 1 January 2014 and 30 June 2021 was performed. Patients were excluded if they were aged <18 years, had linezolid ordered but not administered, were pregnant or were incarcerated. Up to five concurrent SAs were assessed, and dose category was classed as low, moderate or high (dose <33%, 33-66% or >66% of maximum daily dose, respectively). Serotonin toxicity was identified by searching patients' electronic medical records. If identified, the Sternbach criteria and Hunter criteria were applied. RESULTS: Of 2022 patients screened, 1743 were included in this study. Mean age, weight and linezolid duration were 58.5 years, 90.7 kg and 3.8 days, respectively. Approximately 67% (1168/1743) of patients received linezolid with at least one SA, and several patients received multiple SAs. Most patients (53.8%; 616/1144) received moderate- and/or high-dose SAs. Only two patients (0.11%) were identified as possible cases of serotonin toxicity based on the electronic medical record search. However, the incidence of serotonin toxicity was 0.06% (1/1743) based on the Sternbach criteria and 0% (0/1743) based on the Hunter criteria. CONCLUSIONS: Serotonin toxicity among hospitalized patients who received linezolid with or without SAs was exceedingly rare, even among those who received multiple and high-dose SAs.

Kidney transplant candidates' understanding of increased risk donor kidneys: a qualitative study.

BACKGROUND: The Organ Procurement and Transplantation Network (OPTN) requires specific informed consent when "increased risk" (IR) donor organs are utilized. Little is known about kidney transplant candidates' understanding of IR donor kidneys. METHODS: We assessed kidney transplant candidates' perceptions, reasons for accepting or declining a future IR donor kidney offer, and information needs through semi-structured interviews. RESULTS: One hundred and sixty-two (80%) patients participated. Patients perceived IR donors as having poor health (44%), advanced age (38%), and poor kidney quality (24%). Patients (31%) would accept IR donor kidneys to get off dialysis (n=18/50), to improve health by receiving a transplant quickly (n=13/50), and felt that the risk of infection was low (n=10/50). Patients (47%) would decline IR donor kidneys for fear of infection transmission (n=34/76), perceived poor-quality kidneys (n=32/76), and their health was good enough to wait for an average-risk kidney (n=23/76). Undecided patients (22%) needed information about the donation situation. Patients desired information about IR donors, their kidneys, and their impact on patients' health. CONCLUSIONS: Patients confuse risk posed by OPTN-defined IR donors and other non-standard risk donors. Greater efforts are needed to educate kidney transplant candidates about IR donor kidneys and refine terminology used to describe risks to patients.

A rapid assessment of the quality of neonatal healthcare in Kilimanjaro region, northeast Tanzania.

BACKGROUND: While child mortality is declining in Africa there has been no evidence of a comparable reduction in neonatal mortality. The quality of inpatient neonatal care is likely a contributing factor but data from resource limited settings are few. The objective of this study was to assess the quality of neonatal care in the district hospitals of the Kilimanjaro region of Tanzania. METHODS: Clinical records were reviewed for ill or premature neonates admitted to 13 inpatient health facilities in the Kilimanjaro region; staffing and equipment levels were also assessed. RESULTS: Among the 82 neonates reviewed, key health information was missing from a substantial proportion of records: on maternal antenatal cards, blood group was recorded for 52 (63.4%) mothers, Rhesus (Rh) factor for 39 (47.6%), VDRL for 59 (71.9%) and HIV status for 77 (93.1%). From neonatal clinical records, heart rate was recorded for3 (3.7%) neonates, respiratory rate in 14, (17.1%) and temperature in 33 (40.2%). None of 13 facilities had a functioning premature unit despite calculated gestational age <36 weeks in 45.6% of evaluated neonates. Intravenous fluids and oxygen were available in 9 out of 13 of facilities, while antibiotics and essential basic equipment were available in more than two thirds. Medication dosing errors were common; under-dosage for ampicillin, gentamicin and cloxacillin was found in 44.0%, 37.9% and 50% of cases, respectively, while over-dosage was found in 20.0%, 24.2% and 19.9%, respectively. Physician or assistant physician staffing levels by the WHO indicator levels (WISN) were generally low. CONCLUSION: Key aspects of neonatal care were found to be poorly documented or incorrectly implemented in this appraisal of neonatal care in Kilimanjaro. Efforts towards quality assurance and enhanced motivation of staff may improve outcomes for this vulnerable group.

Syphilis-Associated Proteinuria and Hepatitis in the Setting of Human Immunodeficiency Virus (HIV) Co-Infection.

Syphilis has long been known as "the great imitator", mimicking a wide variety of diseases, and often its diagnosis is delayed or missed. It remains an important public health issue that continues to occur at high rates among patients with HIV. We report a case of a 52-year-old man who presented with a constellation of unusual symptoms highlighting that syphilis should be included in the differential diagnosis in patients with HIV presenting with abnormal liver enzymes, rash, proteinuria, conjunctivitis, and/or sexual risk factors.

Longitudinal Effects of Combination Antiretroviral Therapy on Cognition and Neuroimaging Biomarkers in Treatment-Naive People With HIV.

BACKGROUND AND OBJECTIVES: While combination antiretroviral therapy (cART) has dramatically increased the life expectancy of people with HIV (PWH), nearly 50% develop HIV-associated neurocognitive disorders. This may be due to previously uncontrolled HIV viral replication, immune activation maintained by residual viral replication or activation from other sources, or cART-associated neurotoxicity. The aim of this study was to determine the effect of cART on cognition and neuroimaging biomarkers in PWH before and after initiation of cART compared with that in HIV-negative controls (HCs) and HIV elite controllers (ECs) who remain untreated. METHODS: We recruited 3 groups of participants from the University of Rochester, McGovern Medical School, and SUNY Upstate Medical University: (1) ART treatment-naive PWH; (2) age-matched HCs; and (3) ECs. Participants underwent brain MRI and clinical and neuropsychological assessments at baseline, 1 year, and 2 years. PWH were also assessed 12 weeks after initiating cART. Volumetric analysis and fractal dimensionality (FD) were calculated for cortical and subcortical regions. Mixed effect regressions examined the effect of group and imaging variables on cognition. RESULTS: We enrolled 47 PWH, 58 HCs, and 10 ECs. At baseline, PWH had worse cognition and lower cortical volumes than HCs. Cognition improved after initiation of cART and remained stable over time. Greater cortical thickness was associated with better cognition at baseline; greater FD of parietal, temporal, and occipital lobes was associated with better cognition at baseline and longitudinally. At baseline, ECs had worse cognition, lower cortical thickness, and lower FD in all 4 lobes and caudate than PWH and HCs. Greater cortical thickness, hippocampal volumes, and FD of frontal, temporal, and occipital lobes were associated with better cognition longitudinally. DISCUSSION: Initiation of cART in PWH is associated with improvement in brain structure and cognition. However, significant differences persist over time when compared with HCs. Similar trends in ECs suggest that results are due to HIV infection rather than treatment. Stronger associations between cognition and FD suggest this imaging metric may be a more sensitive marker of neuronal injury than cortical thickness and volumetric measures.

Antibody dependent cell cytotoxicity is maintained by the unmutated common ancestor of 6F5, a Gp41 conformational epitope targeting antibody that utilizes heavy chain VH1-2.

In studies on monoclonal IgG antibodies (mAbs) from long-term non-progressors (LTNPs), our laboratory has previously described highly mutated Abs against a complex conformational epitope with contributions from both gp41 the N terminal and C terminal heptad repeat helices. Despite using the VH1-2 gene segment, known to contribute to some of the broadest neutralizing Abs against HIV, members of these Abs, termed group 76C Abs, did not exhibit broad neutralization. Because of the high number of mutations and use of VH1-2, our goal was to characterize the non-neutralizing functions of Abs of group 76C, to assess if targeting of the epitope correlates with LTNP, and to assess the maturation of these Abs by comparison to their predicted common ancestor. Serum competition assays showed group 76C Abs were enriched in LTNPs, in comparison to VRC-01. Specific group 76C clones 6F5 and 6F11, expressed as recombinant Abs, both have robust ADCC activity, despite their sequence disparity. Sequence analysis predicted the common ancestor of this clonal group would utilize the germline non-mutated variable gene. We produced a recombinant ancestor Ab (76Canc) with a heavy chain utilizing the germline variable gene sequence paired to the 6F5 light chain. Competition with group 76C recombinant Ab 6F5 confirms 76Canc binds HIV envelope constructs near the original group C epitope. 76Canc demonstrates comparable ADCC to 6F5 and 6F11 when using gp41 constructs of both clade B and clade C. The functional capability of Abs utilizing germline VH1-2 has implications for disease control and vaccine development.