bluuebunny/crossref_metadata_2025_split huggingface dataset:
G-102 Getting to the last mile in HIV epidemic control
Authors: Mulwanda Jabbin 
Published: April 2019

There is greater global focus on increasing efforts towards the HIV epidemic control. To achieve this, nations should limit the annual number of new HIV infections to less than the number of deaths among people living with HIV.
Dr. Mulwanda discusses the status of the Sub-Saharan Africa epidemic and uses the Zambian approach on being granular and employing targeted, data-driven and cost-efficient approach, in order to reach the last mile. He discusses how taking this scientific evidence to scale requires reorienting HIV program leadership and augmenting health workforce so as to accelerate progress towards HIV Epidemic Control.
I-105 Nonhuman primate models in the study of early events in AIDS virus infection
Authors: Lifson Jeff 
Published: April 2019

Nonhuman primate (NHP) models have proven invaluable for the detailed study of many aspects of AIDS virus pathogenesis difficult or impossible to study with comparable rigor in HIV infected humans. Key aspects of HIV infection in humans can be authentically recapitulated in NHP models. Experimental advantages of NHP models include the ability to exactly control the identity, dose, route, and timing of the viral inoculum employed, control over the timing of initiation and discontinuation of various experimental interventions and the ability to conduct in vivo proof of concept studies of promising but unproven and potentially dangerous treatments. As AIDS virus infection is a tissue based disease, perhaps the most important advantage of NHP models is the ability to obtain extensive longitudinal tissue samples, including from scheduled euthanasia and necropsy with extensive tissue collection and analysis.
Early events in the course of AIDS virus infection are critically important, but difficult to study in HIV infected humans, due to factors that often include delayed diagnosis, and uncertainty about the exact timing of exposure, along with lack of availability of informative tissue specimens. NHP models therefore have an important role to play in the study of early events in AIDS virus infection. Using examples from our recent studies, results will be presented in a series of vignettes demonstrating the utility of NHP models for the study of early events in infection, including: (1) the use of a sequence tagged viral inoculum for tracking independent chains of infection events in vivo involved in mucosal viral transmission and systemic dissemination of infection; (2) the impact of early implementation of combination antiretroviral drug treatment (cART) on limiting the extent of establishment of a durable, recrudescence competent viral reservoir; (3) the contribution of arrest of viral replication at distal sites, after initial dissemination from a mucosal portal of entry, to protection from infection mediated by broadly neutralizing monoclonal antibodies; and iv. the early establishment of expanded clones of CD4+ T cells harboring clonally integrated proviruses that may contribute to the recrudescence competent viral reservoir that persists during cART.
J-105 Novel antiviral targets for HBV elimination
Authors: Hawkins Claudia 
Published: April 2019

Chronic hepatitis B virus (CHB) infection continues to be a major global public health issue despite the availability of effective HBV vaccines. Approximately 257 million people worldwide are infected with CHB and complications from HBV are now a leading cause of morbidity and mortality. The number of deaths from CHB now exceed >1 million per year.
In 2016, the WHO Global health sector strategy on viral hepatitis, announced new goals to achieve a 90% reduction in new cases of HBV and hepatitis C (HCV) and a 65% reduction in mortality due to HBV and HCV by 2030. To achieve the ambitious HBV targets, significant progress is needed in several key intervention areas along the continuum of HBV care including (1) improved access to HBV vaccination and drugs for the prevention of mother to child transmission; (2) more rapid and affordable diagnostics for improved screening and detection of HBV; and (3) innovative therapeutics that can result in HBV cure.
Current recommended therapies for CHB include either pegylated interferon-alpha which stimulates innate immune responses against HBV or oral nucleoside reverse transcriptase inhibitor (NUC) therapies which block the maturation of HBV genome into its infectious form and thus release of infectious virus containing HBV DNA. While both therapies effectively suppress HBV DNA, they rarely result in complete loss of HBsAg, which is needed to achieve functional cure, a serological state associated with a higher remission rate after treatment cessation, and lower rates of cirrhosis and hepatocellular carcinoma. Sterilizing cure is unlikely to be achievable at the current time because of the persistence of the active transcriptional template of HBV covalently closed circular DNA (cccDNA).
Recently there have been promising advances in the treatment of HBV that could potentially achieve widespread functional cure and bring us closer to achieving the ambitious WHO goals of HBV elimination. These include the development of novel therapeutics that target various stages of the HBV lifecycle (eg, HBV entry, viral replication, HBV cccDNA production, and viral protein expression) and immunotherapeutic agents, as well as innovative treatment approaches with existing HBV therapies that seek to maximize the possibility of functional cure. This goal of this talk us to provide a comprehensive overview of these new developments in HBV therapeutics, covering the following key areas: (1) current goals of treatment, and definitions of HBV “cure”; (3) the HBV life cycle, antiviral targets and investigational agents currently being developed that target virus including inhibition of viral entry, HBV surface antigen production and elimination or silencing of cccDNA; and (4) the use of novel surrogate markers (ie, quantitative HBsAg) to assess treatment response in clinical trials.
PC-3 A reappraisal of CTLA-4 checkpoint blockade hypothesis in cancer immunotherapy
Authors: Du Xuexiang , Tang Fei , Liu Mingyue , Zheng Pan , Liu Yang 
Published: April 2019

The classic checkpoint blockade hypothesis states that cancer immunity is restrained by 2 distinct checkpoints: the first is the CTLA-4:B7 interaction that limits priming of naive T cells in lymphoid organs, while the second is the PD-1/B7-H1(PD-L1) interaction that results in exhaustion of effector T cells within the tumor microenvironment. Ipilimumab, a clinically-used so-called immune checkpoint inhibitor (ICI) has been FDA approved for the treatment of metastatic melanoma and might get clinical approval for additional oncological indications, most likely in combination with other drugs, for example anti-PD-1/PD-L1. It is assumed that anti-CTLA-4 antibodies cause tumor rejection by blocking negative signaling from the B7-CTLA-4 interactions.
Surprisingly, at concentrations considerably higher than plasma levels achieved by Ipilimumab blocks neither B7 transendocytosis by CTLA-4 nor CTLA-4 binding to immobilized or cell-associated B7. In Ctla4

h/m
mice expressing both human and mouse CTLA4 genes, anti-CTLA-4 antibodies that bind to human but not mouse CTLA-4 efficiently induce Treg-depletion and Fc receptor-dependent tumor rejection. The blocking antibody L3D10 is comparable to the non-blocking Ipilimumab in causing tumor rejection. Remarkably, L3D10 progenies (HL12/HL32) that lost blocking activity during humanization remain fully competent in Treg depletion and tumor rejection.
We also set out to test 3 commercially available anti-mouse Ctla-4 mAbs(4F10/9H10/9D9) that had been shown to induce tumor rejection for their ability to block the B7-Ctla-4 interaction under physiologically relevant conditions, these data also argue against a role for blocking the B7-Ctla-4 interaction in the induction of antitumor immunity by anti-mouse Ctla-4 mAbs. Since these mAbs showed comparable immunotherapeutic effect and comparable depletion of Treg cells in the tumor microenvironment. Thus, both anti-human CTLA-4 mAbs and anti-mouse CTLA-4 mAbs cause tumor rejection by mechanisms that are independent of checkpoint blockade but dependent on host Fc receptor. These data have important implications for the development of the next generation of immunotherapeutic anti-CTLA-4 mAbs and call for a reappraisal of the checkpoint blockade hypothesis.
PD-1 Genetic risk factors for high-risk human papillomavirus (HPV) infections and persistence among African women
Authors: Adebamowo Sally , Adeyemo Adebowale , Adebamowo Clement 
Published: April 2019

Background:
Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted a genome-wide association study (GWAS) to identify variants associated with hrHPV infection and persistence among women of African ancestry.

Methods:
Participants were 522 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF25/LiPA10. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done under additive genetic models adjusted for age, HIV status and the first 3 principal components of the genotypes.

Results:
The mean (±SD) age of the study participants was 38 (±8) years, 46% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. The GWAS yielded 71 and 107 variants associated with hrHPV infection and persistence, respectively, with suggestive genome-wide significance [P value <1.0 × 10−5]. The top variants (rs149473200, rs147344426, rs151071053 and rs572823632) associated with hrHPV infections are in or near KLF12 [all P = 1.5 × 10−6]. KLF12 is an important regulator of gene expression during carcinogenesis, and it is highly expressed by human immune cells. In several studies, it was associated with HPV and cervical cancer. The top variants associated with persistent hrHPV infections were 3 variants upstream of AL450244 (rs143668247, rs12740341, rs2502139), a cluster of 5 intronic variants in JPH2 (rs116834259, rs74358070, rs11452236, rs79032354, rs6130527) and 2 intronic variants in GPR39 (rs16832308, rs62167448) [all P < 7.0 × 10−7]. These variants are in enhancer histone marks in several tissues and alter the motifs Ets, GATA, NR4A, RXRA, which have been associated with several cancers of the female reproductive system and leiomyosarcomas.

Conclusions:
This exploratory GWAS yielded risk loci that provide clues to the pathogenesis of hrHPV infection and persistence in women of African ancestry. Given the limited sample, larger discovery and replication studies are under way to further characterize the reported associations.
PE-1 Vaginal microbiota composition and persistent high-risk HPV infection in HIV negative and HIV positive women
Authors: Dareng Eileen , Adebamowo Sally , Ma Bing , Ravel Jacques , Pharoah Paul , Adebamowo Clement 
Published: April 2019

Background:
Reports from previous studies suggest that the vaginal microbiota may play a role in cervical HPV pathogenesis. In this study, we examined associations between the vaginal microbiome and persistent high-risk human papillomarvirus (hrHPV) infection among HIV-negative and HIV-positive women.

Methods:
We used 16S rRNA gene amplicon sequencing to characterize the vaginal microbiota in 2 serial mid-vaginal samples taken approximately 6 months apart in 211 Nigerian women and the SPF10LIPA25 system for HPV detection. We used generalized estimating equation (GEE) logistic regression models with robust variance estimation and the cluster option for repeated measures, to evaluate the association between the vaginal microbiota composition and persistent hrHPV infection (defined as being positive for hrHPV at 2 visits 6 months apart); Linear discriminant analysis effect size (LEfSe) to identify phylotype biomarkers of persistent hrHPV; Markov chain transition probabilities to evaluate transition patterns and hierarchical clustering algorithms for community state (CST) assignments.

Results:
Some 142 women were HIV-positive and 69 were HIV-negative. Of the 211 participants, 71 were persistently positive for hrHPV. Mean age (SD) of participants was 38 (8) years. Most participants (84%, 175/211) were premenopausal. High diversity, low Lactobacillus spp. bacterial community state types, CST IV (A and B) were the most prevalent community state types (CST) in HIV-negative (57% at baseline and 40% at the follow-up visit) and HIV-positive (73% at baseline and 65% at the follow-up visit) women. There was effect modification by HIV status (P = 0.02). Among HIV-negative women, those who had a high relative abundance of Lactobacillus spp. were less likely to have persistent hrHPV (OR: 0.35, 95% CI: 0.14 to 0.89, P = 0.03) compared to women with low relative abundance of Lactobacillus spp. LEfSe analysis identified Sneathia spp as being differentially more abundant in HIV-negative women with persistent hrHPV. Markov chain transition probabilities showed that most CST transitions were to the highly diverse, low Lactobacillus spp., CST IV. In HIV-positive women, there was no significant association between the relative abundance of Lactobacillus spp and persistent hrHPV.

Conclusions:
Our results provide evidence to suggest that persistent hrHPV is associated with a lack of Lactobacillus spp in the vaginal microbiota of HIV-negative women.
PG-1 Compromised growth among HIV exposed compared to unexposed children in Nigeria
Authors: Jumare Jibreel , Datong Pam , Osawe Sophia , Okolo Felicia , Inyang Bukola , Abimiku Alash'le 
Published: April 2019

Introduction:
HIV exposed but uninfected (HEU) children may be at an increased risk of impaired growth and development when compared to their unexposed and uninfected (HUU) counterparts. We compared growth pattern between HEU and HUU children in Nigeria.

Methods:
HIV infected and uninfected pregnant women were enrolled at the Plateau State Specialist Hospital (PSSH) Jos Nigeria. Babies born to these mothers were recruited at birth and the mother-infant pairs followed up until 18 months. Weight, length, and head circumference of the babies were measured at each study visit. Age and gender standardized z scores were generated for each anthropometric measure using the World Health Organization Child Growth Standards. Children with length for age (LAZ), weight for age (WAZ) and weight for length (WLZ) z scores <−2 were classified as stunted, underweight, and wasted respectively.

Results:
A total of 415 children (307 HEU and 108 HUU) were included in this analysis. At birth, 117 (28.4%), 9 (2.2%) and 32 (7.8%) babies were stunted, underweight and wasted respectively. In a multivariable longitudinal analysis, the odds of stunting was higher among HEU as compared to HUU children (OR: 2.4 [95% CI: 1.4 to 4.1]; P = 0.001). Similarly, odds of being underweight was higher among the HEU children (OR: 1.6 [95% CI: 1.1 to 2.2]; P = 0.009). While the odds of wasting appeared higher for the HEU children (OR: 1.5 [95% CI: 0.9 to 2.4]; P = 0.128), the difference did not reach statistical significance.

Conclusions:
We found strong evidence of greater impairment of linear and ponderal growth among HEU as compared to HUU children during the first 18 months of life in Nigeria. Further studies are needed to explore the causal basis for these differences.
PG-5 Assessment of knowledge, attitude and practice towards post exposure prophylaxis for HIV among health care workers in Federal Capital Territory, Abuja, Nigeria
Authors: Iowdi Clementina , Olayemi Olayemi , Dung John , Edokwe Chidozie , Okuma James , Peters Samuel , Dakum Patrick , Ekong Ernest 
Published: April 2019

Background:
HIV/AIDS infection in the health care facility is a major health problem in resource limited settings. Health Care Workers (HCW) are caring for a large number of HIV infected patients. This makes them exposed to HIV infection, warranting the use of Post Exposure Prophylaxis (PEP) for HIV very critical. Here we assess Knowledge, Attitude and Practice of HCW towards PEP for HIV.

Methods:
This study was cross-sectional and was conducted among health care workers in 20 health care facilities providing primary health care, secondary, tertiary and private care in June 2018 under the US President Emergency Plan For AIDS Relief (PEPFAR). Data was collected using self-administered questionnaire. Results were summarized in percentages, median and Interquartile range (IQR).

Results:
A total of 195 HCWs completed the survey, 74 (37.9%), 34 (17.4%), 46 (23.6%) and 41 (21.1%) from Primary health care, private, secondary and tertiary health care facilities respectively. Majority of the HCWs were females, 128 (66.7%), 134 (70.2%) were aged 18–39 years and 66 (34.4%) were nurses. The median number of patients seen daily was 28 (IQR 20–50) and the median number of years in practice was 8 (IQR 4–12).
One hundred and seventy-seven (92.7%) HCWs had heard of PEP for HIV and 107 (58.5%) had excellent/good knowledge about PEP for HIV. Majority of HCW 168 (92.8%) had good attitude and would recommend PEP for HIV to others; 150 (81.5%) of HCW consider themselves to be at risk and 88 (46.1%), had occupational exposure. Among those exposed, 75 (85.2%) screened for HIV.
One hundred and sixty-three (86.7%) of the HCW are aware of hospital policy after occupational exposure and 107 (57.6%) would recommend commencing PEP for HIV within 1–72 hours after exposure; 131 (72.4%) are satisfied with current HIV infection protocol at their facility while 177 (92.7%) feel that more training is required for staff on HIV prevention.

Conclusions:
Majority of HCW had excellent/good knowledge, favorable attitude and practice towards PEP for HIV. There is need for policy makers in health sector to put policies, guidelines and pogram that will rapidly scale up PEP for HIV services in health care settings. This is much more important given the increased need for staff at these facilities to multitask and can self-expose. Keywords: Health care workers, Post exposure prophylaxis, HIV.
PI-1 Age-specific HPV prevalence among adolescent girls in Jos, North-Central Nigeria
Authors: Dashe Nanma , Nimzing Lohya , Egah Daniel , Adebamowo Sally , Adebamowo Clement 
Published: April 2019

Background:
Knowledge of the age-specific prevalence of HPV types among adolescent girls in SSA is essential to determine the best age for introduction of HPV vaccination, monitoring of vaccine efficacy and provision of insight into persistent infection.

Methods:
We randomly selected 205 girls, age 9–20 years living in Jos, Nigeria. Informed consent and assent were obtained prior to training on self-collection of vulvo-vaginal samples using sterile swab stick and first void urine. HPV detection was carried out using HPV SPF10-DEIA/LiPA25. Data analysis was done using STATA14.

Results:
The mean (SD) age of the girls was 14.9 (2.3) years. AnyHPV was detected in 29.3% of participants. The earliest age at which anyHPV and high-risk HPV (hrHPV) infections were detected in either urine or vulvo-vaginal samples were 10 and 11 years of age respectively. The prevalence of anyHPV, hrHPV, lrHPV and multiple hrHPV peaked at 16 years of age. The prevalence of hrHPV infection was 3.4% among the 9–12 years age group, 7.8% among 13–16 years and 5.4% among 17–20 year old. The commonest hrHPV types detected were 52 (10.2%), 18 (6.3%) and 51 (4.4%).

Conclusions:
While a larger study is warranted, our findings suggest that in this population, HPV vaccination starting at 9 years of age would cover the at-risk population.
PI-3 Single molecule fluorescence approaches to probe the binding of soluble-CD4 to native-like HIV-1 SOSIP trimers
Authors: Agrawal Parul , DeVico Anthony , Lewis George , Pazgier Marzena , Ray Krishanu 
Published: April 2019

Several lines of evidence suggest that HIV-1 envelope (Env) on virions transition through a series of conformations in solution as well as when they engage CD4 molecules during viral attachment. Moreover, the flexibility and antigenicity of trimers changes as they progressively become saturated with CD4 molecules. HIV-1 Env can potentially engage up to 3 independent CD4 molecules for efficient Env triggering in the virial fusion. However, it is still unknown if one, 2 or 3 CD4 receptor molecules are required for this process. To date, the ensemble techniques and indirect biological assays have been unable to address this question quantitatively. Here, we employed a unique approach utilizing the single molecule detection (SMD) analyses to determine quantitatively the number of sCD4 molecules bound to HIV-1 Env and capture the intermediate interaction states that may be missed by the ensemble methods. A key step in direct counting of single molecules is to ensure single fluorophore labeling of the target molecule. For this purpose, we constructed a C-terminus SNAP-tagged human sCD4 fusion protein and fluorescently labeled it with a single Alexa 488 fluorophore (sCD4-SNAP-A488). This approach was devoid of any genetic or external perturbation to the SOSIP.664 trimers.
Our results by SMD confirm that up to 3 sCD4-SNAP-A488 molecules bind a single SOSIP trimer and provide insight into trimer occupancy shifts over time. The experimental data reveals that Env is intrinsically dynamic, transitioning between 3 distinct stoichiometries (1-, 2- and 3-sCD4 bound states). Real-time single molecule association kinetic experiments divulge different states of trimer triggering and stoichiometry of the complexes. We have developed an algorithm for automated analyses of our data to infer the stoichiometry in real-time. Importantly, our single-molecule based association kinetic analysis indicates that assemblies of trimer with 1 or 3 sCD4 molecules are more stable whereas binding of 2 sCD4s seems transitional. Our findings are consistent with structural information available for conformations of HIV-1 Env in its ligand-free, prefusion state and in the CD4-bound states and provide new critical insights into the sCD4 interaction with the Env for better understanding of the complex biology of HIV-1 entry into cells.
Opioid-prescribing Patterns for Pediatric Patients in the United States
Authors: Groenewald Cornelius B. 
Published: April 2019

Background and Objectives:
The opioid crisis in America affects both adults and children. However, knowledge about the epidemiology of the opioid crisis, opioid prescribing patterns, and the link between opioid prescribing and problematic opioid behaviors remain limited. Thus, children are often excluded from health care policies and guidelines aimed at curbing the opioid crises. The primary aim of this topical review is to provide a brief overview of the opioid crises affecting children, followed by a synopsis of recent research on opioid prescribing patterns and data on the links between legitimate opioid use and risk for problematic opioid use behaviors.

Methods:
This is a narrative review.

Results:
Opioid misuse is a public health crisis facing children and adolescents in the United States and serves as a key antecedent for other problematic opioid behaviors, including opioid use disorder, heroin use, and opioid overdose. Furthermore, the United States experienced a significant increase in opioid prescribing to children and adolescents as compared with prescribing rates before the year 2000. Yet, data on the associations between opioid prescribing patterns and risk for problematic opioid use remains limited.

Discussion:
There exist an urgent need to identify adolescents at increased risk for problematic opioid use behaviors following a receipt of medically prescribed opioids. The article closes with some general guidelines that providers may follow to reduce the risk of opioids in pediatric patients.