bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Incident Circumcision Lead to Risk Compensation? Evidence From a Population Cohort in KwaZulu-Natal, South Africa
Authors: Ortblad Katrina F. , Harling Guy , Chimbindi Natsayi , Tanser Frank , Salomon Joshua A. , Bärnighausen Till 
Published: December 2018

Background:
Voluntary medical male circumcision reduces men's risk of HIV acquisition and may thus increase HIV risk-related sexual behaviors through risk compensation. We analyze longitudinal data from one of Africa's largest population cohorts using fixed-effects panel estimation to measure the effect of incident circumcision on sexual behaviors.

Setting:
KwaZulu-Natal, South Africa.

Methods:
An open population cohort of men was followed from 2009 to 2015. Men self-reported their circumcision status and sexual behavior annually. We used linear regression models with individual-level fixed effects to measure the effect of incident circumcision on recent sex (past 12 months) and sexual behaviors that increase HIV risk (not using a condom at last sex, never using condoms with the most recent sexual partner, concurrent sexual partners at present, and multiple sexual partners in the past 12 months). We controlled for potential time-varying confounders: calendar year, age, education, and sexual debut.

Results:
The 5127 men in the cohort had a median age of 18 years (interquartile range 16–24) at cohort entry. Over the study period, almost 1 in 5 of these men (19.4%) became newly circumcised. Incident circumcision affected neither recent sex [percentage point (PP) change 0.0, 95% confidence interval: −1.2 to 1.3] nor sexual behaviors that increase HIV risk (PP −1.6, 95% confidence interval: −4.5 to 1.4).

Conclusions:
The data from this study strongly reject the hypothesis that circumcision affects sexual risk-taking. Risk compensation should not serve as an argument against increased and accelerated scale-up of circumcision in this and similar communities in South Africa.
Vulnerable Periods: Characterizing Patterns of Sexual Risk and Substance Use During Lapses in Adherence to HIV Pre-exposure Prophylaxis Among Men Who Have Sex With Men
Authors: Wray Tyler B. , Chan Philip A. , Kahler Christopher W. , Simpanen Erik M. , Liu Tao , Mayer Kenneth H. 
Published: December 2018

Background:
Pre-exposure prophylaxis (PrEP) is highly efficacious, but some groups of men who have sex with men may have difficulty adhering to daily dosing. Prevention-effective adherence suggests that PrEP's efficacy depends on adherence at the time of HIV exposure; yet, few studies have examined how exposures (ie, high-risk sex) overlap with periods of consecutive missed PrEP doses. Substance use may also play a role in these vulnerable periods.

Methods:
We used digital pill bottles to monitor the daily adherence of 40 PrEP-experienced patients recruited from an outpatient clinic in the Northeastern US over a six-month period. Participants also completed detailed online diaries every 2 weeks during this time that surveyed their sexual behavior and substance use each day.

Results:
Daily adherence was high overall (M = 83.9%, SD = 18.0%), but 53% (N = 21) had a lapse of > 3 consecutive daily PrEP doses over 6 months. Participants' rate of engaging in high-risk condomless anal sex (CAS) did not differ across lapse days versus continuously adherent days. Alcohol use was not associated with engaging in CAS during a PrEP lapse. However, participants reported engaging in CAS significantly more often during a PrEP adherence lapse on days when they also used stimulant drugs.

Conclusions:
Men who have sex with men may have periodic difficulty adhering to PrEP at the specific times when they are at risk. Stimulant drug use could play an important role in increasing HIV risk specifically during adherence lapses.
Serological Assessment of 18 Pathogens and Risk of AIDS-Associated Non-Hodgkin Lymphoma
Authors: Halec Gordana , Waterboer Tim , Brenner Nicole , Butt Julia , Hardy W. David , D'Souza Gypsyamber , Wolinsky Steven , Macatangay Bernard J. , Pawlita Michael , Detels Roger , Martínez-Maza Otoniel , Hussain Shehnaz K. 
Published: December 2018

Background:
HIV infection is associated with increased susceptibility to common pathogens, which may trigger chronic antigenic stimulation and hyperactivation of B cells, events known to precede the development of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL).

Methods:
To explore whether cumulative exposure to infectious agents contributes to AIDS-NHL risk, we tested sera from 199 AIDS-NHL patients (pre-NHL, average lead time 3.9 years) and 199 matched HIV-infected controls from the Multicenter AIDS Cohort Study, for anti-IgG responses to 18 pathogens using multiplex serology. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression models.

Results:
We found no association between cumulative exposure to infectious agents and AIDS-NHL risk (OR 1.01, 95% CI: 0.91 to 1.12). However, seropositivity for trichodysplasia spinulosa polyomavirus (TSPyV), defined as presence of antibodies to TSPyV capsid protein VP1, was significantly associated with a 1.6-fold increase in AIDS-NHL risk (OR 1.62, 95% CI: 1.02 to 2.57). High Epstein–Barr virus (EBV) anti-VCA p18 antibody levels closer to the time of AIDS-NHL diagnosis (<4 years) were associated with a 2.6-fold increase in AIDS-NHL risk (OR 2.59, 95% CI: 1.17 to 5.74). In addition, high EBV anti-EBNA-1 and anti-ZEBRA antibody levels were associated with 2.1-fold (OR 0.47, 95% CI: 0.26 to 0.85) and 1.6-fold (OR 0.57, 95% CI: 0.35 to 0.93) decreased risk of AIDS-NHL, respectively.

Conclusions:
Our results do not support the hypothesis that cumulative exposure to infectious agents contributes to AIDS-NHL development. However, the observed associations with respect to TSPyV seropositivity and EBV antigen antibody levels offer additional insights into the pathogenesis of AIDS-NHL.
Human Immunodeficiency Virus Increases the Risk of Incident Heart Failure
Authors: Yen Yung-Feng , Ko Ming-Chung , Yen Muh-Yong , Hu Bor-Shen , Wang Teng-Ho , Chuang Pei-Hung , Lai Hsin-Hao , Chen Chu-Chieh , Deng Chung-Yeh 
Published: December 2018

Background:
Although the HIV can cause myocardial inflammation, the association of HIV infection with subsequent development of heart failure (HF) has not been extensively studied. This nationwide cohort study aimed to determine the risk of incident HF in people living with HIV/AIDS (PLWHA).

Methods:
We identified PLWHA using the Taiwan Centers for Disease Control and Prevention HIV Surveillance System. An age- and sex-matched control group without HIV infection was selected from the Taiwan National Health Insurance Research Database for comparison. All patients were followed up until December 2014 and were observed for a new diagnosis of HF. A time-dependent Cox proportional hazards model was used to determine the association of HIV and highly active antiretroviral therapy with incident HF, with death as a competing risk event.

Results:
Of the 120,765 patients (24,153 PLWHA and 96,612 matched controls), 641 (0.53%) had incident HF during a mean follow-up period of 5.84 years, including 192 (0.79%) PLWHA and 449 (0.46%) controls. Time to diagnosis of incident HF was significantly shorter in PLWHA than in those without HIV infection (P < 0.001, the log-rank test). After adjusting for age, sex, and comorbidities, HIV infection was found to be an independent risk factor for incident HF (adjusted hazard ratio, 1.52; 95% confidence interval: 1.27 to 1.82). As the duration of highly active antiretroviral therapy increased, the risk of HF decreased (P = 0.014).

Conclusions:
HIV infection was an independent risk factor for incident HF. Clinicians need to be aware of the higher risk of HF in PLWHA.
Early and Late Virologic Failure After Virologic Suppression in HIV-Infected Asian Children and Adolescents
Authors: Mu Weiwei , Bartlett Adam W. , Bunupuradah Torsak , Chokephaibulkit Kulkanya , Kumarasamy Nagalingeswaran , Ly Penh Sun , Hansudewechakul Rawiwan , Nguyen Lam Van , Lumbiganon Pagakrong , Sudjaritruk Tavitiya , Mohamed Thahira A. Jamal , Yusoff Nik Khairulddin Nik , Truong Khanh Huu , Do Viet Chau , Fong Moy Siew , Nallusamy Revathy , Kurniati Nia , Wati Dewi Kumara , Sohn Annette H. , Kariminia Azar , Zhang Fujie ,   for the TREAT Asia Pediatric HIV Observational Database of IeDEA Asia-Pacific
Published: December 2018

Background:
Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving.

Setting:
An Asian cohort in 16 pediatric HIV services across 6 countries.

Methods:
From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA ≥1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA ≥1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure.

Results:
Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor–based regimens, and early virologic failure. No risk factors were identified for early virologic failure.

Conclusions:
Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required.
A Clinical Prediction Rule for Protease Inhibitor Resistance in Patients Failing Second-Line Antiretroviral Therapy
Authors: Cohen Karen , Stewart Annemie , Kengne Andre P. , Leisegang Rory , Coetsee Marla , Maharaj Shavani , Dunn Liezl , Hislop Michael , van Zyl Gert , Meintjes Graeme , Maartens Gary 
Published: December 2018

Background:
Most adults with virological failure on second-line antiretroviral therapy (ART) in resource-limited settings have no major protease inhibitor (PI) resistance mutations. Therefore, empiric switches to third-line ART would waste resources. Genotypic antiretroviral resistance testing (GART) is expensive and has limited availability. A clinical prediction rule (CPR) for PI resistance could rationalize access to GART.

Setting:
A private sector ART cohort, South Africa.

Methods:
We identified adults with virologic failure on ritonavir-boosted lopinavir/atazanavir-based ART and GART. We constructed a multivariate logistic regression model including age, sex, PI duration, short-term adherence (using pharmacy claims), concomitant CYP3A4-inducing drugs, and viral load at time of GART. We selected variables for the CPR using a stepwise approach and internally validated the model by bootstrapping.

Results:
148/339 (44%) patients had PI resistance (defined as ≥ 1 major resistance mutation to current PI). The median age was 42 years (interquartile range 36–48), 212 (63%) were females, 308 (91%) were on lopinavir/ritonavir, and median PI duration was 2.6 years (interquartile range 1.6–4.7). Variables associated with PI resistance and included in the CPR were age {adjusted odds ratio (aOR) 1.96 (95% confidence interval [CI]: 1.42 to 2.70) for 10-year increase}, PI duration (aOR 1.14 [95% CI: 1.03 to 1.26] per year), and adherence (aOR 1.22 [95% CI: 1.12 to 1.33] per 10% increase). The CPR model had a c-statistic of 0.738 (95% CI: 0.686 to 0.791).

Conclusions:
Older patients with high adherence and prolonged PI exposure are most likely to benefit from GART to guide selection of a third-line ART regimen. Our CPR to select patients for GART requires external validation before implementation.
Brief Report: Surveillance of Congenital Anomalies After Exposure to Raltegravir or Elvitegravir During Pregnancy in the United Kingdom and Ireland, 2008–2018
Authors: Rasi Virginia , Cortina-Borja Mario , Peters Helen , Sconza Rebecca , Thorne Claire 
Published: December 2018

Background:
The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV have to be carefully balanced with the risks of embryo–fetal toxicities due to fetal exposure to maternal ART. The recent report of a potential safety signal with dolutegravir use in pregnancy and potential increased rate of neural tube defects has raised the question of a potential class effect for integrase strand inhibitors. To contribute real-world evidence, we evaluated data on pregnant women receiving raltegravir (RAL) or elvitegravir (EVG) in the United Kingdom and Ireland.

Methods:
The National Study of HIV in Pregnancy and Childhood is a comprehensive population-based surveillance study collecting data on all HIV-positive pregnant women and their children. We collected data on all pregnancies exposed to an ART regimen containing RAL or EVG resulting in live birth, stillbirth, and induced abortion with an expected date of delivery between September 2008 and April 2018. Pregnancies were stratified into 3 groups of earliest exposure.

Results:
A total of 908 pregnancies were exposed to a RAL- or EVG-based regimen (875 to RAL and 33 to EVG). There were 886 live-born infants exposed to RAL, 8 pregnancies ended in stillbirth, and 9 in induced abortions. Among the 886 live-born infants, there were 23 (2.59%, 95% confidence interval: 1.65 to 3.86) reported congenital anomalies, 2 nervous system defects but no reported neural tube defects. Of the 33 pregnancies exposed to EVG, 31 resulted in live-born infants with no congenital anomaly and the remaining 2 pregnancies ended in induced abortion.

Conclusions:
The prevalence of congenital anomalies is consistent with national population estimates for 2008–2016 in the United Kingdom. More data are needed on safety of RAL and EVG in pregnancy.
Peripheral Blood Mitochondrial DNA Copy Number Obtained From Genome-Wide Genotype Data Is Associated With Neurocognitive Impairment in Persons With Chronic HIV Infection
Authors: Hulgan Todd , Kallianpur Asha R. , Guo Yan , Barnholtz-Sloan Jill S. , Gittleman Haley , Brown Todd T. , Ellis Ronald , Letendre Scott , Heaton Robert K. , Samuels David C. ,   for the CHARTER Study
Published: December 2018

Background:
Mitochondrial DNA (mtDNA) copy number varies by cell type and energy demands. Blood mtDNA copy number has been associated with neurocognitive function in persons without HIV. Low mtDNA copy number may indicate disordered mtDNA replication; high copy number may reflect a response to mitochondrial dysfunction. We hypothesized that blood mtDNA copy number estimated from genome-wide genotyping data is related to neurocognitive impairment (NCI) in persons with HIV.

Methods:
In the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study, peripheral blood mtDNA copy number was obtained from genome-wide genotyping data as a ratio of mtDNA single-nucleotide polymorphism probe intensities relative to nuclear DNA single-nucleotide polymorphisms. In a multivariable regression model, associations between mtDNA copy number and demographics, blood cell counts, and HIV disease and treatment characteristics were tested. Associations of mtDNA copy number with the global deficit score (GDS), GDS-defined NCI (GDS ≥ 0.5), and HIV-associated neurocognitive disorder (HAND) diagnosis were tested by logistic regression, adjusting for potential confounders.

Results:
Among 1010 CHARTER participants, lower mtDNA copy number was associated with longer antiretroviral therapy duration (P < 0.001), but not with d-drug exposure (P = 0.85). mtDNA copy number was also associated with GDS (P = 0.007), GDS-defined NCI (P < 0.001), and HAND (P = 0.002). In all analyses, higher mtDNA copy number was associated with poorer cognitive performance.

Conclusions:
Higher mtDNA copy number estimated from peripheral blood genotyping was associated with worse neurocognitive performance in adults with HIV. These results suggest a connection between peripheral blood mtDNA and NCI, and may represent increased mtDNA replication in response to mitochondrial dysfunction.
Copy-Years Viremia and Risk of Virological Failure in Long-Term–Treated HIV Patients
Authors: Falasca Francesca , De Vito Corrado , Mazzuti Laura , di Carlo Daniele , Celani Luigi , Fimiani Caterina , d'Ettorre Gabriella , Mezzaroma Ivano , Antonelli Guido , Turriziani Ombretta 
Published: December 2018

Background:
Viremia copy-years (VCY) is associated with mortality and disease outcome prediction. This study evaluated the association of VCY with virological failure (VF), defined as a plasma viral load (pVL) >400 copies/mL, and with single levels of viremia.

Methods:
Eight hundred and fifty antiretroviral therapy (ART)-treated patients with pVL < 37 copies/mL [target not detected or target detected (TD)] or >37, but less than 200 copies/mL (low-level viremia), and at least 6-pVL measures during 54 months of follow-up were selected. VCY was calculated individually over the follow-up as the area under pVL curve. Pearson's χ2 test was used to analyze differences in VCY quartiles distribution between groups.

Results:
Higher VCY values were detected in patients with low-level viremia {294 copy-years [interquartile range (IQR): 99–1870]} than in TD [52 copy-years (IQR: 53–153)] and target not detected groups [19 copy-years (IQR: 8–54)]. VCY was also significantly different between patients with undetectable viremia and patients with basal pVL TD (P < 0.001). Pearson's χ2 test revealed a significant association between VCY and basal levels of viremia (P < 0.0001). In addition, the risk of VF rose with increasing VCY (Hazard ratio 1.01, 95% confidence interval: 1.01 to 1.02).

Conclusions:
This study revealed the association of VCY with VF and with single levels of viremia suggesting that, despite the success of ART, minimal residual viremia may cause the cumulative viral burden to rise. Full viral load suppression during ART is crucial to limit the increase in VCY.
Climate explains population divergence in drought-induced plasticity of functional traits and gene expression in a South AfricanProtea
Authors: Akman Melis , Carlson Jane E. , Latimer Andrew M. 
Published: December 2018

AbstractLong term environmental variation often drives local adaptation and leads to trait differentiation across populations. Additionally, when traits change in an environment-dependent way through phenotypic plasticity, the genetic variation underlying plasticity will also be under selection. These processes could create a landscape of differentiation across populations in traits and their plasticity. Here, we studied drought responses in seedlings of a shrub species from the Cape Floristic Region, the common sugarbush (Protea repens). We measured morphological and physiological traits, and sequenced whole transcriptomes in 8 populations that represent both the climatic and the geographic distribution of this species. We found that there is substantial variation in how populations respond to drought, but we also observed common patterns such as reduced leaf size and leaf thickness, and upregulation of stress- and down-regulation of growth-related gene groups. Both high environmental heterogeneity and milder source site climates were associated with higher plasticity in various traits and co-expression gene networks. Associations between traits, trait plasticity, gene networks and the source site climate suggests that temperature may play a bigger role in shaping these patterns when compared to precipitation, in line with recent changes in the region due to climate change. We also found that traits respond to climatic variation in an environment dependent manner: some associations between traits and climate were apparent only under certain growing conditions. Together, our results uncover common responses ofP. repenspopulations to drought, and climatic drivers of population differentiation in functional traits, gene expression and their plasticity.
Metagenome-wide measurement of protein synthesis in the human fecal microbiota using MetaRibo-Seq
Authors: Fremin Brayon J. , Bhatt Ami S. 
Published: December 2018

AbstractThe healthy human fecal microbiota is too diverse to comprehensively study with the current throughput of proteomic methods. Shotgun sequencing technologies allow for much more comprehensive profiling. Here, we develop and apply MetaRibo-Seq, a method for simultaneous ribosome profiling of multiple taxa within a complex bacterial community. This approach captures taxonomic diversity in fecal samples. As expected, the detected ribosome-bound transcripts are relatively enriched within coding regions and significantly correlate to detectable protein abundances. In a low diversity fecal sample, we show that MetaRibo-Seq is more strongly correlated than metatranscriptomic data to protein abundance. This significant correlation of metatranscriptomics and MetaRibo-Seq with protein levels is maintained, though with decreased strength as taxonomic diversity increases. Finally, we identify genes that are consistently regulated at the translational level across bacterial taxa within fecal communities. In conclusion, MetaRibo-Seq enables comprehensive translational profiling in complex bacterial communities for the first time.
De novo aging-related megaloneurites: alteration of NADPH diaphorase positivity in the sacral spinal cord of the aged dog
Authors: Li Yinhua , Jia Yunge , Hou Wei , Wei Zichun , Wen Xiaoxin , Tian Yu , Zhang Weijin , Bai Lu , Guo Anchen , Du Guanghui , Tan Huibing 
Published: December 2018

AbstractThe aging-related changes of NADPH-diaphorase (NADPH-d) in the spinal cord were studied in aged dogs. At all levels of the spinal cord examined, NADPH-d activities were present in neurons and fibers in the superficial dorsal horn, dorsal commissure and in neurons around the central canal. In addition, the sympathetic autonomic nucleus in the thoracic and rostral lumbar segments exhibited prominent NADPH-d cellular staining whereas the sacral parasympathetic nucleus (SPN) in the sacral segments was not well stained. Interestingly, we found abundant NADPH-d positive enlarged-diameter fibers termed megaloneurite, which characteristically occurred in the aged sacral segments, distributed in the dorsal gray commissure (DGC), lateral collateral pathway (LCP) the lateral fasciculi and the central canal compared with the cervical, thoracic and lumbar segments. The dense, abnormal NADPH-d megaloneurites occurred in extending from dorsal entry zone through lamina I along with the lateral boundary of the dorsal horn to the region of the SPN. These fibers were prominent in the S1-S3 segments but not in adjacent segments L5-L7 and Cx1 or in thoracolumbar segments and cervical segments. Double staining with GFAP, NeuN, CGRP, MAP2 and Iba1, NADPH-d megaloneurite colocalized with vasoactive intestinal peptide. Presumably, the megaloneurites may represent, in part, visceral afferent projections to the SPN and/or DGC. The NADPH-d megaloneurites in the aged sacral spinal cord indicated some anomalous changes in the neurites, which might account for a disturbance in the aging pathway of the autonomic and sensory nerve in the pelvic visceral organs.