bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recess environment and curriculum intervention on children’s physical activity: IPLAY
Authors: Nigg Claudio R , Kutchman Eve , Amato Katie , Schaefer Christine A , Zhang Guangxiang , Anwar Md Mahabub Ul , Anthamatten Peter , Browning Raymond C , Brink Lois , Hill James 
Published: April 2018

Abstract
Understanding the impacts of the built environment on physical activity (PA) is essential to promoting children’s PA. The purpose of this study was to investigate the effects of schoolyard renovations and a PA recess curriculum alone and in combination on children’s PA. This was a 2 (learning landscape [LL] vs. non-LL) × 2 (curriculum intervention vs. no curriculum intervention) factorial design with random assignment to the curriculum intervention, and six elementary schools per condition. PA outcomes were assessed preprogram, mid-program, immediate postprogram, and one year postprogram. No meaningful intervention effects were found. Lack of an effect may be due to the brief dose of recess, the curriculum not being integrated within the schoolyard, the LL implementation occurring prior to the study, or the already high levels of PA. Potential avenues to promote PA include making recess longer, integrating recess into the school curricula, and developing recess PA curricula integrating schoolyards.
A-107 Early ART and HIV Remission: Experience from the RV254 and related HIV remission studies
Authors: Ananworanich Jintanat 
Published: April 2018

Early antiretroviral therapy (ART) is an important step in the path towards an HIV cure. Acute HIV infection studies have demonstrated the ability to identify and treat very early infection in adults, resulting in significantly smaller HIV reservoirs, preserved immune functions with little viral escape to immune pressure. These results have been illustrated in the ongoing RV254 acute HIV infection study in Thailand that has enrolled close to 500 individuals. It has served as a platform to learn the effects of early ART and recruit participants for HIV remission trials.
Despite the favorable qualities, the majority of early treated individuals do not achieve HIV remission. Indeed this has been the experience to date in the RV254 HIV remission trials, which include 3 completed studies and one ongoing, with others in development. The interventions have included latency-reversing agent, broadly neutralizing antibody and therapeutic HIV vaccine. However, there are important lessons to be learned that would inform the design of future HIV remission trials.
There continues to be exciting new development of immune-based interventions. It is highly likely that combination therapies that can generate persistent and effective immune responses to control HIV will be required for a durable ART-free sustained remission of HIV.
B-102 Results from a First-In-Human study with BNZ-1, a novel, selective inhibitor of IL-2, IL-9, and IL-15 at the common gamma-chain receptor, in clinical development for the treatment of HAM/TSP and T-cell malignancies
Authors: Frohna Paul , Tagaya Yutaka , Ratnayake Anoshie , Doerr Nick , Basheer Asjad , Al-Mawsawi Laith , Kim Woo Jae , Zapata Juan 
Published: April 2018

Aberrant signaling of IL-2, IL-9, and IL-15, members of the γγγc cytokine family, is involved in multiple human diseases (eg, T-cell malignancies, GvHD, HAM/TSP) that are not effectively or safely treated by the currently available anti-cytokine approaches.
BNZ-1 is a selective inhibitor of IL-2, IL-9 and IL-15 signaling through γγc, without altering IL-4, -7, or -21. In this open-label, single-dose study (NCT03046459), 18 healthy adults (n = 3/dose) received a single IV dose of 0.2, 0.4, 0.8, 1.6, 3.2 or 6.4 mg/kg and were monitored for 30 days. BNZ-1 was well-tolerated with a good safety profile (no serious/severe AEs, no DLTs, and no clinically-significant changes on labs, vital signs or ECGs).
BNZ-1 exposure was dose proportional with an elimination t1/2 of ∼5 days, supporting weekly or every other week dosing. PD activity was characterized by flow cytometry of Tregs (IL-2), NK cells (IL-15) and CD8+ central memory T-cells (Tcm; IL-2 & IL-15) in PBMCs from days 4, 15 and 31. Tregs were decreased by 50%–60% after doses of 0.4–1.6 mg/kg on day 4 and by 80%–93% at 3.2 and 6.4 mg/kg on day 15. On day 4 NK cells decreased by 20%, 40% and 60% at 0.2, 0.4 and 0.8 mg/kg, respectively, and plateaued at 70%–80% decreases at doses a1.6 mg/kg. Tcm were decreased at day 4 for the top 3 doses that continued to decline to day 15 when all doses, except 0.2 mg/kg, showed a mean decrease ranging from 10% to 81% that trended with dose. Tregs, NK cells, and Tcm returned to/toward baseline by day 31. CD4+ and CD8+ T-cells, B-cells, and monocytes were unchanged at all time points.
These clinical data suggest that BNZ-1 is a highly-active, selective immunomodulator that safely decreases Tregs, NKs and Tcm, while sparing the major leukocyte populations.
P-E5 Whole genome deep sequencing of HIV reveals extensive multi-class drug resistance in Nigerian patients failing first-line antiretroviral therapy
Authors: Ndembi Nicaise , Elbouzidi Kate , Kwaghe Vivian , Ogbanufe Obinna , Murtala-Ibrahim Fati , Charurat Man , Dakum Patrick , Sabin Caroline 
Published: April 2018

Background:
Whole genome deep sequencing (WGS) could improve understanding of treatment failure and the emergence of resistance by revealing the distribution of mutations throughout the viral population over time.

Methods:
Adult patients receiving 1L ART (2 NRTI and 1 NNRTI) at the University of Abuja Teaching Hospital, Nigeria, were included if they had experienced virological failure (HIV-1 RNA >1000 copies/mL, at least 6 months after ART initiation, confirmed by clinician-driven testing), and had a stored plasma sample available for WGS.

Results:
Sixty participants were sampled during 1L failure (73% female; median age 30 (interquartile ratio [IQR] 28–35); median CD4+ cell count 110 cells/mm3 (IQR 63–191); median 28 months after ART initiation (IQR 18–41)). At 1L failure, 57% of participants had thymidine analogue mutations (TAMs), with 30% harbouring 3 or more TAMs, 95% had other (non-TAM) NRTI mutations and 100% had NNRTI mutations. The most common mutations were M184V, Y181C, G190A, K65R and K103N. Overall, 17% (61/367) of the mutations identified were low-level minority variants (present at 2%–20% of the intra-host viral population), which would not have been detected by standard resistance testing methods, 24% (88/367) were present at 20%–90% frequency, and 59% (218/367) were dominant majority variants representing >90% of the participant's viral population.

Conclusions:
Diverse Nigerian HIV clades exhibit multi-class drug resistance at 1LART failure. The predominance of high-frequency mutations suggests that emergent resistance had become fixed in the viral population by the time of sampling.
P-E6 Hepatitis B and Hepatitis C: Viral infections among pregnant women in some Nigerian major cities: A review
Authors: Itelima Janet 
Published: April 2018

Background:
Worldwide, viral hepatitis is the commonest cause of hepatitis dysfunction in pregnancy. During pregnancy, viral hepatitis is associated with high risk of maternal complications and has become a leading cause of foetal death.

Aim:
This review was done to assess the status of hepatitis B and hepatitis C viral infection among pregnant women in some Nigerian major cities.

Methodology:
The information used for this review was from published works in Nigeria and elsewhere. The information was extracted over the period of 7 months from November 2015 to June 2017.

Results:
In Nigeria, the prevalence of hepatitis B and Hepatitis C viral infection is on the increase and the nation has been classified among the group of countries endemic for the infection with about 18 million of the populace infected. The prevalence of hepatitis B viral infection among pregnant women in many parts of the country has been reported; with Port Harcourt having the prevalence of (4.9%), Yenagoa (5.3%), Benin (12.5%) Jos (10.3%, 15.9% and 23.9%), Ibadan (21.3%). Anti-HCV antibody prevalence among pregnant women has also been reported in various parts of Nigeria; with Benin having the prevalence of (3.6%), Yenagoa (0.5%), Osogbo (9.2%), Enugu (14.9%), Jos (5.2%), Kaduna (11.9%), Kano (7.3%) and Zaria (18.2%). In Nigeria, the transmission of hepatitis B and Hepatitis C viral infections occur mainly during childhood as a result of maternal-neonatal transmission and by other risk factors like blood transfusion, sexual promiscuity, history of sharing of toothbrush, sharp objects such as razor blades, nail cutters and scissors and instruments for pedicure and manicure. Other modes of the viral infection common in the country include high risk groups such as health care workers, poor socioeconomic status. Thus, all the risk factors implicated elsewhere in the spread of the viral infections in the general population also play role in Nigeria.

Conclusion:
The prevalence of hepatitis B virus (HBV) and Hepatitis C virus (HCV) among pregnant women in Nigeria is of intermediate endemicity. Therefore, there is the need to institute public health measures such as routine screening of all pregnant women's blood and blood products for hepatitis, personal and environmental sanitation, and the discouragement of unsupervised injections to reduce disease burden and transmission in the population.
P-I1 Monotherapy with integrase inhibitors does not maintain viral suppression in humanized mice with chronic HIV infection
Authors: Heredia Alonso , Hassounah Said , Medina-Moreno Sandra , Zapata Juan , Le Nhut , Han Yingshan , Foulke James , Davis Charles 
Published: April 2018

Introduction and Methods:
Simplification of current triple ART to dual ART or monotherapy may suffice to maintain HIV suppression while sparing drug toxicities. We evaluated and compared the efficacy of 20-week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIVBaL. Plasma HIV RNA was measured by qRT-PCR (limit of detection of 150 copies/40 μL plasma) and drug levels by LC/MS/MS. Escape viruses were genotyped and analyzed for replication capacity and drug susceptibility in tissue culture.

Results:
Drug untreated control mice maintained constant viremia throughout the study. Virus isolates from these mice were susceptible to both raltegravir (EC50 <8 nM) and dolutegravir (EC50 <1 nM). Mice treated with raltegravir or dolutegravir had plasma drug levels comparable to those in humans. Monotherapy with raltegravir initially suppressed HIV viremia, but failed to maintain suppression in 4/4 mice. Viruses from raltegravir failing mice had the G140S and Q148H/K substitutions, and were resistant to both raltegravir (EC50 values of >100 nM) and dolutegravir (EC50 values ranging 8.8–13.3 nM) in drug susceptibility assays using human PBMCs. Monotherapy with dolutegravir suppressed viremia in 5/5 of mice, but viremia rebounded in one animal after 12 weeks of treatment. The virus from this mouse had mutations E138K, G140S, Q148H, N155H and S230R, was highly resistant to both raltegravir (EC50 >1000 nM) and dolutegravir (EC50 of 550 nM), and replicated to high levels in PBMCs.

Discussion:
Raltegravir or dolutegravir monotherapy does not ultimately maintain HIV suppression in humanized mice, suggesting that dual therapy will most likely be required for simplification of ART treatment. Eleven (OR = 10.93) & 7 (OR = 6.53) times more likely respectively, to have HIV negative infants compared to prophylaxis regimen.

Conclusion:
HAART prior to and during pregnancy is associated with an increased likelihood of achieving a favorable EID result.
P-D6 Elevated plasma HIV RNA level is associated with impaired neurocognitive function among HIV-1 infected patients in Nigeria
Authors: Jumare Jibreel , El-Kamary Samer , Magder Laurence , Hungerford Laura , Umlauf Anya , Cherner Mariana , Abimiku Alash'le , Charurat Man 
Published: April 2018

Introduction:
Plasma HIV RNA level has been shown to correlate with HIV disease progression, morbidity and mortality. We examined the association between levels of plasma HIV RNA and cognitive function among patients in Nigeria.

Methods:
A total of 179 HIV-1 infected participants with available plasma HIV RNA results and followed longitudinally for up to 2 years were included in this study. Blood samples from participants were used for the measurement of plasma HIV RNA and CD4+ T cell count. Utilizing demographic and practice effect adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS a 0.5 indicating cognitive impairment.

Results:
In a longitudinal multivariable linear regression analysis, adjusting for CD4 cell count, Beck's depression score, age, gender, years of education, and antiretroviral treatment status, global T scores decreased by 0.35 per log10 increase in Plasma HIV RNA (p = 0328). Adjusting for the same variables in a multivariable logistic regression, the odds of neurocognitive impairment were 30% higher per log10 increase in plasma HIV RNA (OR: 1.28 [95% CI: 1.08 to 1.51]; p = 0.0048). There were statistically significant associations for the speed of information processing, executive and verbal fluency domains in both linear and logistic regression analyses.

Conclusion:
We found a significant association between plasma HIV RNA levels and cognitive function in both baseline (cross-sectional) and longitudinal analyses. However, the latter was significantly attenuated, and appeared to be driven largely by strong associations among antiretroviral naive individuals.
P-E2 The Impact of structured mentor mother support on retention during the first 12 months postpartum among HIV positive women in rural Nigeria
Authors: Fan-Osuala Chinenye , Ramadhani Habib , Erekaha Salome , Anaba Udochisom , Nwanne Gift , Bathnna Miriam , Charurat Manhattan , Sam-Agudu Nadia 
Published: April 2018

Introduction:
With the advent of lifelong therapy, interventions that sustain long-term engagement with PMTCT services are needed. We evaluated the impact of a structured peer support program on postpartum PMTCT retention among rural Nigerian women.

Methods:
This prospective cohort study enrolled HIV+ pregnant women from 20 primary healthcare centers (PHCs). Ten PHCs with structured mentor mother (MM) support (training, supervision, client tracking, standard documentation and performance evaluation) were pair-matched with 10 routine unstructured peer support (PS) PHCs. Participants received viral load at 6 months and were followed up to 12 months postpartum. Viral suppression was defined as <20 copies/mL. Retention assessment was based on monthly and bi-monthly clinic visits in the first and second 6 month postpartum periods respectively. Participants with ≥5 of 9 expected visits were considered retained. A logistic regression model with generalized estimating equation was used to evaluate the effect of PS and other factors on retention.

Results:
Of 497 women enrolled, 260 and 237 were exposed to MM and routine PS respectively. Women with MM support (aOR = 6.6, 95% CI 3.4 to 13.1) and viral suppression at 6 months (aOR = 3.1, 95% CI 1.8 to 5.6) had higher odds of retention during the 12 month postpartum period. Age, distance from PHC, religion, gravidity, disclosure & time of diagnosis had no effect on retention.

Discussion:
Structure in peer support programs improved retention. Also, viral suppression had an independent effect on retention, indicating a strong link between adherence and sustained engagement; both being essential for PMTCT.

Conclusion:
Built-in structure can significantly enhance the impact of PS interventions on PMTCT outcomes.
C-101 Production and properties of SOSIP trimers
Authors: Moore John 
Published: April 2018

I will review the progress of our team's projects to produce GMP-quality SOSIP trimers in amounts and quantities appropriate for human clinical trials. The BG505 SOSIP.664 GMP-project has now been completed successfully, yielding ~5 g of trimers. A follow-up on effort to make the germline–bNAb targeting BG505 SOSIP. v4.1-GT1.1 trimer is well underway, using the same core methodologies. The latter trimer was designed at the Amsterdam Medical Center and is very similar to one recently described by Medina-Ramirez et al in J Exp Med.
This project stems from our NIH-funded HIVRAD grant program and the translation phase has been supported and managed by the BMGF and IAVI, reflecting the three funding agencies working together towards a common goal.
D-106 Chromatin Functional States Correlate with the Reversal of Latently HIV-1 Infected Primary CD4+ T cells
Authors: Battivelli Emilie , Dahabieh Matthew S. , Abdel-Mohsen Mohamed , Svensson J. Peter , Da Silva Israel Tojal , Cohn Lilian B. , Gramatica Andrea , Deeks Steven , Greene Warner , Pillai Satish K. , Verdin Eric 
Published: April 2018

Current antiretroviral therapies (ART) do not allow for the eradication of the human immunodeficiency virus (HIV) due to the presence of latent proviruses in rare, long-lived resting CD4+ T cells. The main research efforts to eliminate the viral reservoir are focused on the use of latency reversing agents (LRAs) to force the reactivation of the latent provirus, while maintaining ART to prevent de novo infections. Subsequently, reactivation of HIV expression would kill reservoir cells via viral cytopathic effects and/or immune clearance (“shock and kill” strategy). So far, no LRAs tested in clinical trials have succeeded in reducing the reservoir. Furthermore, there is limited understanding as to why some latent proviruses are being induced, while others are not.
We used an improved dual-fluorescent HIV reporter (GKO), which distinguishes productively infected cells from the latent population, to investigate the efficacy of the “shock and kill” strategy. In addition, GKO provides a unique opportunity to (1) explore the impact of HIV integration site specificity on the fate of the infection, and to (2) characterize the inducible subpopulation of latently infected cells, since it allows the isolation of inducible latent and non-inducible latent populations from the productively infected majority.
We first showed that our patients' data was consistent with previously published studies. However, we found that at most 5% of GKO latent proviruses were reactivated. Moreover, the analysis of HIV-1 integration sites from productively, non-inducible and inducible latently infected populations reveals heterogeneity within the latent infections. In contrast to non-inducible latent infections, the integration sites of inducible latent proviruses have similar features to those of productive proviruses, thus demonstrating a prominent role for the site of integration and its chromatin context for the fate of the initial infection as well as for latency reversal.
Our study shows an important roadblock for the “shock and kill” approach to reservoir eradication. Differences between inducible and permanently latent reservoir cells suggest that complete reservoir reactivation and eradication with LRAs may prove impossible, and that a multipronged “functional cure” approach may be necessary.
D-111 Influence of age on immune response to influenza vaccination in virologically suppressed HIV infected persons
Authors: Pallikkuth Suresh , deArmas Lesley , Rinaldi Stefano , Georgr Varghese , Pahwa Rajendra , Pahwa Savita 
Published: April 2018

Background:
Approximately 5%–20% of the US population contracts influenza infection annually with >200,000 hospitalizations and >35,000 deaths that occur mainly in older adults. We investigated determinants of immune response to influenza vaccine in relation to aging and concurrent HIV infection.

Methods:
154 HIV infected (HIV+) virologically controlled persons on ART and 161 HIV uninfected (HIV−) grouped by age as young (<40 years), middle aged (40–59 years) and old (≥60 years) were given trivalent influenza vaccination. Serological responses to influenza vaccine antigens were correlated with cellular immune activation (IA), plasma markers of inflammation, and immune phenotype and function of peripheral leukocytes, including peripheral T follicular helper cells (pTffh).

Results:
Absolute responders with >4 fold increase in titer to all the vaccine antigens were fewer in HIV+ (14%) than in HIV− (32%), lower in old compared to young, and inversely correlated with age for Ab to H1N1 and B antigen. Several immunologic markers were negative predictors of the vaccine response in HIV infection; these included higher levels of activated pTfh, monocytes expressing inflammatory marker CD11b, activated naive B cells, checkpoint inhibitor Tim3 on CD4 T cells and high plasma sCD25. Positive correlations were found with frequencies of bulk and antigen specific pTfh cells exhibiting high IL-21 and low IL-2 expression and lacking in inflammatory cytokines (TNFa, IL17) production. Although more deficiencies were evident in HIV+ old compared to other groups, the differences between HIV+ and HIV− for Ab responses and immunologic markers were maximal in young age.
E-102 Policy, practice and science in Nigeria: Implementing evidence based research for HIV programming in Nigeria
Authors: Adewole Isaac F. 
Published: April 2018

Nigeria with a population of over 180 million currently has a national estimate of 3% prevalence of HIV infection. Briefly, 3 million people are living with HIV; 160,000 pregnant women living with HIV and pediatric HIV infection account for about 30% of global burden. Following the assumption of office by President Muhammadu Buhari in 2015, the country initiated plan and began an aggressive drive in revitalizing the healthcare system towards attainment of Universal Health Coverage in the country.
This presentation will chronicle policies, practices and evidences generated in-country on biology of HIV infection, transmission and management as well other non-orthodox claims of cure. The socio-cultural interpretations, perceptions and behaviours as it affects HIV infection within Nigerian space will be highlighted. The concluding section of the presentation will focus on key priority areas of HIV programming and research that requires international collaborations.
G-103 Regulation of HTLV-1 proviral latency
Authors: Bangham Charles 
Published: April 2018

The human leukaemia virus HTLV-1 causes chronic inflammatory disease or an aggressive T-cell malignancy in about 10% of infected people. The risk of these diseases is strongly correlated with the proviral load, which frequently exceeds 10% of peripheral blood mononuclear cells. The high proviral load is limited by a strong, chronically activated host immune response. HTLV-1 does not release cell-free virions, but propagates both within and between hosts by cell-to-cell contact, via the virological synapse.
Until recently, HTLV-1 was thought to be latent in vivo, and persisted chiefly by continuous oligoclonal proliferation of about 100 clones of HTLV-1-infected CD4+ T cells. However, we have shown that a typical individual carries between 104 and 105 clones, and the proviral load–the chief correlate of disease–is determined by the number of clones, not by oligoclonal proliferation. We recently discovered that HTLV-1 alters host chromatin structure in the infected cell, by binding the chromatin architectural protein CTCF, which regulates higher-order chromatin structure and gene expression in vertebrates. Thus, HTLV-1 does a remarkable experiment of nature, by changing the conformation of chromatin in tens of thousands of different ways in each infected host. Two broad questions are raised: first, how does CTCF benefit the virus? Second, how does the change in chromatin structure affect the host? I will show that the abnormal chromatin looping caused by CTCF can deregulate host gene expression and so may act as an oncogenic driver. I will also present evidence that HTLV-1 plus-strand is expressed in intense, intermittent bursts, and that expression minus strand is not, as is currently believed, constitutive.