bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Preexposure Prophylaxis Cascades to Assess Implementation in Australia: Results From Repeated, National Behavioral Surveillance of Gay and Bisexual Men, 2014–2018
Authors: Holt Martin , Lee Evelyn , Lea Toby , Bavinton Benjamin , Broady Tim , Mao Limin , MacGibbon James , Keen Phillip , Murphy Dean , Bear Brandon , Crawford David , Ellard Jeanne , Kolstee Johann , Power Cherie , Prestage Garrett , Grulich Andrew , Guy Rebecca , de Wit John 
Published: January 2020

Background:
HIV prevention cascades can assist in monitoring the implementation of prevention methods like preexposure prophylaxis (PrEP). We developed 2 PrEP cascades for Australia's primary HIV-affected population, gay and bisexual men.

Methods:
Data were drawn from 2 national, repeated, cross-sectional surveys (the Gay Community Periodic Surveys and PrEPARE Project). One cascade had 3 steps, and the other had 7 steps. Trends over time were assessed using logistic regression. For the most recent year, we identified the biggest drop between steps in each cascade and compared the characteristics of men between the 2 steps using multivariate logistic regression.

Results:
Thirty-nine thousand six hundred and seventy non–HIV-positive men participated in the Periodic Surveys during 2014–2018. PrEP eligibility increased from 28.1% (1901/6762) in 2014 to 37.3% (2935/7878) in 2018 (P < 0.001), awareness increased from 29.6% (563/1901) to 87.1% (2555/2935; P < 0.001), and PrEP use increased from 3.7% (21/563) to 45.2% (1155/2555; P < 0.001). Of 1038 non–HIV-positive men in the PrEPARE Project in 2017, 54.2% (n = 563) were eligible for PrEP, 97.2% (547/563) were aware, 67.6% (370/547) were willing to use PrEP, 73.5% (272/370) had discussed PrEP with a doctor, 78.3% (213/272) were using PrEP, 97.2% (207/213) had recently tested, and 75.8% (157/207) reported reduced HIV concern and increased pleasure because of PrEP. The break point analyses indicated that PrEP coverage was affected by geographical availability, education level, employment, and willingness to use PrEP.

Conclusions:
PrEP eligibility, awareness, and use have rapidly increased among Australian gay and bisexual men. The cascades identify disparities in uptake by eligible men as a result of socioeconomic factors and PrEP's acceptability.
Pattern and Frequency of Seroreactivity to Routinely Used Serologic Tests in Early-Treated Infants With HIV
Authors: Puthanakit Thanyawee , Ananworanich Jintanat , Akapirat Siriwat , Pattanachaiwit Supanit , Ubolyam Sasiwimol , Assawadarachai Vatcharain , Sawangsinth Panadda , Jupimai Thidarat , Anugulruengkitt Suvaporn , Tawan Monta , Kosalaraksa Pope , Borkird Thitiporn , Suntarattiwong Piyarat , Kanjanavanit Suparat , de Souza Mark S. ,   on behalf of the RV475/HIV-NAT209 Study Group
Published: January 2020

Background:
Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection.

Methods:
Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2–5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies.

Results:
The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3–6 months (N = 15) showed a greater frequency (range: 53%–93%) and breadth (median and range: 3 [1–4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%–61% and breadth (1 [0–4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay.

Conclusions:
These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.
HIV Status Disclosure and Sexual Transmission Risks Among People Who Are Living With HIV and Receiving Treatment for Non-HIV Sexually Transmitted Infections, Cape Town, South Africa
Authors: Kalichman Seth , Mathews Catherine , Banas Ellen , Kalichman Moira 
Published: January 2020

Background:
HIV status disclosure to sex partners potentially reduces the risk of sexually transmitting HIV. However, there is limited information on the associations between HIV status disclosure in types of sexual partnerships and ensuing sexual practices.

Methods:
We examined HIV status disclosure to sex partners among 205 men and women living with HIV and receiving diagnostic and treatment services for a co-occurring sexually transmitted infection (STI) in Cape Town, South Africa. Participants completed partner-by-partner sexual behavior interviews and provided permission to extract recurrent STI clinic visits over the subsequent 12 months.

Results:
Three groups were formed on the basis of HIV status disclosure to sex partners: (1) 22% reported only HIV same-status partners, (2) 26% had HIV-negative or unknown HIV status (HIV different status) sex partners to whom they had disclosed their HIV status, and (3) 52% had at least one HIV different-status partner to whom they had not disclosed. There were no associations between HIV status disclosure and demographic characteristics, sexual practices, or recurrent STI clinic visits. Undisclosed HIV status to at least one HIV different-status sex partner was associated with greater alcohol use and less likelihood of receiving antiretroviral therapy; participants who were least likely to disclose their HIV status to partners drank more alcohol and were less likely to be taking antiretroviral therapy.

Conclusions:
High prevalence of partner nondisclosure and lack of significant correlates to HIV status disclosure indicate a need for further research with an eye toward identifying disclosure processes and mechanisms that may ultimately lead to effective interventions.
Brief Report: Persistence of Non-Vaccine Oncogenic HPV Genotypes in Quadrivalent HPV-Vaccinated Women Living With HIV
Authors: McClymont Elisabeth , Coutlée François , Lee Marette , Albert Arianne , Raboud Janet , Walmsley Sharon , Lipsky Nancy , Loutfy Mona , Trottier Sylvie , Smaill Fiona , Klein Marina B. , Yudin Mark H. , Harris Marianne , Wobeser Wendy , Bitnun Ari , Samson Lindy , Money Deborah ,   for the CTN 236 HPV in HIV Study Team
Published: January 2020

Background:
Human papillomavirus (HPV) vaccines have promising safety and immunogenicity data in women living with HIV (WLWH). However, it is critical to understand the residual burden of oncogenic HPV within WLWH to inform postvaccination cervical screening needs. We assessed rates of persistent infection with nonquadrivalent HPV (qHPV) oncogenic types in a cohort of qHPV-vaccinated WLWH.

Setting:
Multicentre, longitudinal cohort across Canada.

Methods:
WLWH were scheduled to receive 3 doses of qHPV vaccine. Participants provided health data and HPV DNA samples. Persistent cases of HPV were defined as new HPV in samples from ≥2 consecutive visits or as HPV present in the last sample. HPV31/33/35/39/45/51/52/56/58/59/68/82 were considered to have oncogenic potential. Median follow-up time was 4 years after initial vaccine dose.

Results:
A total of 284 participants were eligible for this analysis with 1205 person-years (PY) of follow-up (≥1 dose of vaccine, ≥1 HPV DNA result after vaccination). The highest incidence of persistent infection was with HPV51 (1.38/100 PY), followed by HPV52 (1.18/100 PY), and HPV39 (1.06/100 PY). The incidence of persistent infection with pooled HPV types added in the nonavalent vaccine (HPV31/33/45/52/58) was lower than the incidence of persistent oncogenic HPV types not contained within available vaccines (HPV35/39/51/56/59/68) (2.4/100 PY versus 3.6/100 PY, respectively).

Conclusions:
qHPV-vaccinated WLWH continue to face a burden of persistent oncogenic HPV infection. Although the nonavalent vaccine could alleviate some of this burden, 2 of the top 3 persistent oncogenic HPVs in this cohort are not contained within any available vaccine. This highlights the need for ongoing cervical screening in HPV-vaccinated WLWH.
Brief Report: Improving Early Infant Diagnosis Observations: Estimates of Timely HIV Testing and Mortality Among HIV-Exposed Infants
Authors: Webb Karen , Chitiyo Vivian , Mahachi Nyikadzino , Huruva Mukungunugwa Solomon , Mushavi Angela , Zizhou Simukai , Engelsmann Barbara , Abbas Ferrand Rashida , Neuman Melissa , Hartogensis Wendy , Geng Elvin 
Published: January 2020

Background:
Improving efforts toward elimination of mother-to-child transmission of HIV requires timely early infant diagnosis (EID) among all HIV-exposed infants, but the occurrence of timely EID and infant survival may be underascertained in routine, facility-bound program data.

Methods:
From March 2015 to May 2015, we traced a random sample of HIV-positive mother and HIV-exposed infant pairs lost to follow-up for EID in facility registers in Zimbabwe. We incorporated updated information into weighted survival analyses to estimate incidence of EID and death. Reasons for no EID were surveyed from caregivers.

Results:
Among 2651 HIV-positive women attending antenatal care, 1823 (68.8%) infants had no documented EID by 3 months of age. Among a random sample of 643 (35.3%) HIV-exposed infants lost to follow-up for EID, vital status was ascertained among 371 (57.7%) and updated care status obtained from 256 (39.8%) mothers traced. Among all HIV-infected mother–HIV-exposed infant pairs, weighted estimates found cumulative incidence of infant death by 90 days of 3.9% (95% confidence interval: 3.4% to 4.4%). Cumulative incidence of timely EID with death as a competing risk was 60%. The most frequently cited reasons for failure to uptake EID were “my child died” and “I didn't know I should have my child tested.”

Conclusions:
Our findings indicate uptake of timely EID among HIV-exposed infants is underestimated in routine health information systems. High, early mortality among HIV-exposed infants underscores the need to more effectively identify HIV-positive mother–HIV exposed infant pairs at high risk of adverse outcomes and loss to follow-up for enhanced interventions.
Negative Diagnostic PCR Tests in School-Aged, HIV-Infected Children on Antiretroviral Therapy Since Early Life in Johannesburg, South Africa
Authors: Patel Faeezah , Thurman Cara , Liberty Afaaf , Burke Megan , Strehlau Renate , Shiau Stephanie , Coovadia Ashraf , Abrams Elaine J. , Violari Avy , Kuhn Louise 
Published: January 2020

Background:
Younger age at antiretroviral therapy (ART) initiation has been associated with smaller HIV reservoirs. We investigated whether younger age of ART initiation is associated with testing negative and weaker signal on a standard HIV diagnostic test in treated children.

Methods:
At exit from a longitudinal study at 2 sites in Johannesburg, South Africa, 316 school-aged, HIV-infected children on continuous ART started at a median age of 6.3 months, were tested with standard total nucleic acid PCR used for infant diagnosis. All negative results were repeated. Simultaneous viral load (VL) and CD4+ T-cell counts/percentages, along with data collected over the prior 4 years, were used in multivariable regression to predict negative PCR results and higher cycle threshold (Ct) values (weaker signal).

Results:
Seven children (2.2%, 95% confidence interval: 0.6 to 3.8) in the full cohort had negative PCR results; all 7 were in a subset of 102 (6.9%, 95% confidence interval: 2.0 to 11.8) who had initiated ART at age 0–4 months and had VL <50 copies/mL at the time of PCR testing. Only one repeat tested as negative. Younger age at ART initiation, VL <50 copies/mL at time of test, sustained VL <400 copies/mL, lower CD4+ T-cell counts, and ever treated with efavirenz were significant predictors of weaker signal on the diagnostic test.

Conclusions:
In a small proportion of children who start ART in the first months of life and remain on continuous therapy, standard diagnostic HIV PCR tests may result as negative. Repeat testing may resolve uncertainty of diagnosis.
Immunological and Virological Responses in Older HIV-Infected Adults Receiving Antiretroviral Therapy: An Evidence-Based Meta-Analysis
Authors: Zhang Qi , Yu Xiaowen , Wu Tong , Shang Hong , Jiang Yongjun 
Published: January 2020

Background:
Millions of people living with the HIV have received antiretroviral therapy (ART). Older adults make up a significant portion of these individuals; however, the immunological and virological responses to ART for older patients still need to be clarified.

Design:
Meta-analysis.

Methods:
In this article, we systematically reviewed research articles published between 2001 and 2018 that reported immunological and virological responses and AIDS-related mortality among HIV- infected adults (including individuals aged 50 years and older) receiving ART, using meta-analysis. ART efficiency was measured using 3 outcomes: (1) immunological response, (2) virological response, and (3) mortality.

Results:
We identified 4937 citations, and 40 studies were eventually selected to investigate ART efficiency in older HIV-infected patients, comprising more than 888,151 patients initiating ART. We report that older patients showed poor immunological responses, with CD4 counts and the restoration of CD4 counts after ART initiation being significantly lower than seen in younger patients. However, older patients exhibited better viral suppression rates (risk ratio: 1.04; 95% confidence intervals: 1.01 to 1.08) after 36 months following ART initiation. In addition, older adults had a higher risk of AIDS-related death (adjusted hazard ratio: 1.44, 95% confidence interval: 1.30 to 1.60).

Conclusions:
Older age after ART initiation was associated with a poorer immunological response and a higher risk of mortality, suggesting the need to increase early diagnosis and treatment among older HIV patients.
Characterizing Viral Load Burden Among HIV-Infected Women Around the Time of Delivery: Findings From Four Tertiary Obstetric Units in Gauteng, South Africa
Authors: Moyo Faith , Haeri Mazanderani Ahmad , Murray Tanya , Technau Karl-G. , Carmona Sergio , Kufa Tendesayi , Sherman Gayle G. 
Published: January 2020

Background:
Elimination of mother-to-child transmission of HIV requires sustained viral load suppression during pregnancy and breastfeeding among women living with HIV (WLHIV). Antenatal antiretroviral therapy coverage is reported at >95% in South Africa, but viral load suppression rates are unknown. We describe maternal VL burden around time of delivery at 4 tertiary obstetric units (TOUs) in Gauteng Province.

Methods:
Between June 2018 and March 2019, routine point-of-care (PoC) maternal HIV VL and early infant diagnosis (EID) testing were implemented at 3 TOUs in Johannesburg and 1 in Tshwane district. WLHIV and HIV-exposed neonates were eligible for HIV VL (Xpert HIV-1 VL) and EID (Xpert HIV-1 EID or m-PIMA HIV1/2 detection) testing around time of delivery, respectively. Proportions of viremic women and intrauterine (IU)-infected neonates were calculated among valid PoC results.

Results:
Among 8147 live births to WLHIV, 2769 (34.0%) women and 4333 (53.2%) neonates had valid PoC results. Median VL at delivery was <40 copies/mL (interquartile range: 0–398). The proportion of women with a VL < 50, 50 to <1000, and ≥1000 copies/mL was 63.6%, 13.9% and 22.4%, respectively. There were 65/4333 (1.5%) IU-infected neonates. Among 1449 mother–neonate pairs with both VL and EID results, IU transmission by VL threshold was 3/946 (0.3%), 6/187 (3.2%), and 25/316 (7.9%) for VL < 50, 50 to <1000, and ≥1000 copies/mL, respectively (P < 0.001).

Conclusions:
Despite high antiretroviral therapy coverage, >1/3 of WLHIV had a VL ≥50 copies/mL at delivery. Among mother–neonate pairs, maternal VL ≥50 copies/mL accounted for 31/34 (91%) IU infections. Improvement in the quality of HIV care among WLHIV is essential if South Africa is to achieve elimination of mother-to-child transmission.
Raltegravir (RAL) in Neonates: Dosing, Pharmacokinetics (PK), and Safety in HIV-1–Exposed Neonates at Risk of Infection (IMPAACT P1110)
Authors: Clarke Diana F. , Acosta Edward P. , Cababasay Mae , Wang Jiajia , Chain Anne , Teppler Hedy , Popson Stephanie , Graham Bobbie , Smith Betsy , Hazra Rohan , Calabrese Kat , Bryson Yvonne , Spector Stephen A. , Lommerse Jos , Mirochnick Mark ,   the IMPAACT P1110 Protocol Team
Published: January 2020

Background:
Adequate pharmacokinetic and safety data in neonates are lacking for most antiretroviral agents. Raltegravir is a selective HIV-1 integrase strand transfer inhibitor available in a granule formulation suitable for use in neonates and young infants as prophylaxis or treatment of HIV infection.

Methods:
IMPAACT P1110 is a phase 1, multicenter, noncomparative dose-finding study of raltegravir in infants exposed to HIV-1 infection. A 2-cohort adaptive design was utilized where pharmacokinetic data from infants in cohort 1 who received 2 single doses of raltegravir 3 mg/kg were included in population modeling and simulations to guide selection of a daily dose for infants in cohort 2.

Results:
A total of 52 infants enrolled in IMPAACT 1110: cohort 1 (N = 16) and cohort 2 (N = 36). Using simulations based on population PK modeling incorporating cohort 1 data, the following daily dosing regimen was selected for study: 1.5 mg/kg daily from birth through day 7; 3 mg/kg twice daily from days 8–28 of life; and 6 mg/kg twice daily after 4 weeks of age through 6 weeks of age. The geometric mean protocol exposure targets for AUC, Ctrough, and Cmax were met or slightly exceeded in all infants. The chosen neonatal raltegravir dosing regimen was safe and well tolerated in full-term neonates during treatment over the first 6 weeks of life and follow-up to age 24 weeks.

Conclusions:
Raltegravir can be safely administered to full-term infants using the daily dosing regimen studied. This regimen is not recommended for use in premature infants in a new version of P1110.
Skeletofacial Reconstruction for Cleft-Related Deformities
Authors: Denadai Rafael , Chou Pang-Yun , Pai Betty C. J. , Chen Chit , Cheng-Hui Lin Clement , Huang Chiung-Shing , Chen Yu-Ray , Lo Lun-Jou 
Published: January 2020

Abstract
Skeletofacial reconstruction in skeletally mature patients with cleft lip/palate can be challenging because of multifaceted condition-specific anatomical features in addition to several repercussions from surgical intervention during the growing period. This surgical report presents the history and evolving philosophy of cleft-skeletofacial reconstruction at the Chang Gung Craniofacial Center, a referral center for cleft care in Taiwan. The maximization of satisfactory function and the appearance outcome-burden ratio have been the fundamental aims for this team to develop and upgrade cleft-skeletofacial reconstruction over the past 4 decades, with more than 10,000 mature patients treated. The study highlights key lessons learned in outcome-based and patient-oriented changes over time until the current approach, which focuses on patient-centered care with a comprehensive, multidisciplinary, and team-based model. Substantial advances in surgical, orthodontic, anesthetic, and computer imaging aspects have contributed to improving and optimizing the correction of a broad spectrum of facial and occlusal deformities while ensuring safety, predictability, efficiency, and stability in outcomes. Understanding the development and refinement of cleft-skeletofacial reconstruction over the time and transferring these time-tested and scientifically validated protocols and principles to clinical practice may serve as a reliable foundation to continue the advancement and enhancement of the delivery of surgical cleft care worldwide.
True and Average Internal Nasal Valve Area in Septorhinoplasty
Authors: Zeina Ahmed M. , El Zeheiry Ahmed M. , Bahaa El-Din Ahmed M. 
Published: January 2020

Abstract
The internal nasal valve provides most of the upper airway resistance; therefore, many surgical techniques have been developed to reconstruct and widen this sensitive area of the nasal airway. Twenty patients participated in this study to compare the effects of 2 techniques (spreader grafts and modified spreader flap) on the true valve area and the average valve area after rhinoplasty according to standard axial computed tomography on admission and 6 months following the surgery. The mean follow-up time was 10.2 months. After rhinoplasty, the average valve area increased in all patients who underwent the spreader graft or modified spreader flap techniques. The preoperative average valve areas for patients undergoing the spreader graft and spreader flap techniques were (37.10 ± 16.45 mm2) and (36.86 ± 10.56 mm2), respectively, whereas the postoperative results were (48.58 ± 12.85 mm2) for those who underwent the spreader graft technique and (56.22 ± 19.06 mm2) for those who underwent the modified spreader flap technique. Both techniques resulted in significant radiological and clinical improvement with a good correlation between the subjective and objective tests.

Level of Evidence
IV.
Redox response of iron-sulfur glutaredoxin GRXS17 activates its holdase activity to protect plants from heat stress
Authors: Martins Laura , Knuesting Johannes , Bariat Laetitia , Dard Avilien , Freibert Sven A. , Marchand Christophe H. , Young David , Dung Nguyen Ho Thuy , Debures Anne , Saez-Vasquez Julio , Lemaire Stéphane D. , Lill Roland , Messens Joris , Scheibe Renate , Reichheld Jean-Philippe , Riondet Christophe 
Published: January 2020

ABSTRACTLiving organisms use a large panel of mechanisms to protect themselves from environmental stress. Particularly, heat stress induces misfolding and aggregation of proteins which are guarded by chaperone systems. Here, we examine the function the glutaredoxin GRXS17, a member of thiol reductases families in the model plantArabidopsis thaliana. GRXS17 is a nucleocytosolic monothiol glutaredoxin consisting of an N-terminal thioredoxin (TRX)-domain and three CGFS-active site motif-containing GRX-domains that coordinate three iron-sulfur (Fe-S) clusters in a glutathione (GSH)-dependent manner. As a Fe-S cluster-charged holoenzyme, GRXS17 is likely involved in the maturation of cytosolic and nuclear Fe-S proteins. In addition to its role in cluster biogenesis, we showed that GRXS17 presents both foldase and redox-dependent holdase activities. Oxidative stress in combination with heat stress induces loss of its Fe-S clusters followed by subsequent formation of disulfide bonds between conserved active site cysteines in the corresponding TRX domains. This oxidation leads to a shift of GRXS17 to a high-MW complex and thus, activates its holdase activity. Moreover, we demonstrate that GRXS17 is specifically involved in plant tolerance to moderate high temperature and protects root meristematic cells from heat-induced cell death. Finally, we showed that upon heat stress, GRXS17 changes its client proteins, possibly to protect them from heat injuries. Therefore, we propose that the iron-sulfur cluster enzyme glutaredoxin GRXS17 is an essential guard to protect proteins against moderate heat stress, likely through a redox-dependent chaperone activity. All in all, we reveal the mechanism of an Fe-S cluster-dependent activity shift, turning the holoenzyme GRXS17 into a holdase that prevents damage caused by heat stress.