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We performed this study to better understand women's views of the breast screening experience in order to improve the rate of uptake and the service offered. The sample comprised 27 women aged over 50 who had attended a regional breast screening service and received normal results. Data were collected through four focus groups. Results showed a need for a local, easily accessible breast screening unit with free car park facilities. Thus, women preferred a mobile screening unit that had a 'cosy, nonclinical' atmosphere. Staff were reported to be efficient, caring, and helpful. Nonetheless, all women reported discomfort during the mammogram, and the nature of the procedure, during which women had their breasts squashed between two plates, was unexpected. Furthermore, women expressed anxiety about results, receiving recall letters, and about cancer in general. Women suggested the service should be advertised more widely and wanted more detailed information before and during screening. They demonstrated altruistic concern for other women who are currently excluded from the screening programme. [ABSTRACT FROM AUTHOR]

Introduction: To describe the changes in the Lung Information Needs Questionnaire (linq) score after an educational intervention in patients with chronic respiratory disease in an outpatient pulmonary rehabilitation (pr) program from Cali, Colombia, between November 2011 and April 2012. Materials and methods: Quasi-experimental study. The linq questionnaire was used to assess the need for education and to design the educational component that consisted of individual and group educational sessions twice a week. At the end of the RP program, the change generated in the domains of the linq was determined. Results: Of 61 participants, 21 completed the 2 phases of the study; 51.7 % were female, mean age was 55 (sd 15), 38.1 % were single and 47.6 % were primary school. The linq score pre-rehabilitation was 9.4 (sd 3.5) and post-rehabilitation 5.8 (sd 2.5), with statistically signifIcant differences (p < 0.05) in all domains, except for medicament. Conclusion: 100 % of the patients needed some degree of educational information at the beginning of the pr. The educational program for this population resulted in improvement of the linq score at the end of the rehabilitation.

Mr. Smith is an 85-year-old nursing home patient who has suffered from dementia for the past eight years. He has been bed bound and uncommunicative for the last six months. He was admitted with aspiration pneumonia three times in the past year. Over the last few months he has lost weight due to poor dietary intake and has developed a decubitus ulcer. Mr. Smith's family inquires about the advantages and disadvantages of the placement of a percutaneous endoscopic gastrostomy (PEG) tube to help improve his weight loss. [ABSTRACT FROM AUTHOR]

Abstract Background Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT) and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, c-KIT mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/- RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/- RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI) and overall survival times (OS) of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone. Results Histologic grade 3 MCTs, MCTs with c-KIT mutations, MCTs with increased cytoplasmic KIT, and MCTs with increased Ki67 and AgNOR values were associated with decreased DFI and OS. Dogs with histologic grade 3 MCT had significantly increased DFI and OS when treated with chemotherapy vs. surgery alone. Although not statistically significant due to small sample sizes, MCTs with c-KIT mutations had increased DFI and OS when treated with chemotherapy vs. surgery alone. Conclusion and clinical importance This study confirms the prognostic value of histologic grade, c-KIT mutations, KIT staining patterns, and proliferation analyses for canine MCT. Additionally, the results of this study further define the benefit of postoperative vinblastine and prednisone for histologic grade 3 MCTs.

Abstract Background Pulmonary neuroendocrine cells (PNEC) are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Methods Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1) undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5), sensory nerves (calcitonin gene related peptide, CGRP), and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP). The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. Results PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP) was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Conclusion Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

Abstract Background Middle ear disease (otitis media) is common and frequently severe in Australian Aboriginal children. There have not been any recent large-scale surveys using clear definitions and a standardised middle ear assessment. The aim of the study was to determine the prevalence of middle ear disease (otitis media) in a high-risk population of young Aboriginal children from remote communities in Northern and Central Australia. Methods 709 Aboriginal children aged 6–30 months living in 29 communities from 4 health regions participated in the study between May and November 2001. Otitis media (OM) and perforation of the tympanic membrane (TM) were diagnosed by tympanometry, pneumatic otoscopy, and video-otoscopy. We used otoscopic criteria (bulging TM or recent perforation) to diagnose acute otitis media. Results 914 children were eligible to participate in the study and 709 were assessed (78%). Otitis media affected nearly all children (91%, 95%CI 88, 94). Overall prevalence estimates adjusted for clustering by community were: 10% (95%CI 8, 12) for unilateral otitis media with effusion (OME); 31% (95%CI 27, 34) for bilateral OME; 26% (95%CI 23, 30) for acute otitis media without perforation (AOM/woP); 7% (95%CI 4, 9) for AOM with perforation (AOM/wiP); 2% (95%CI 1, 3) for dry perforation; and 15% (95%CI 11, 19) for chronic suppurative otitis media (CSOM). The perforation prevalence ranged from 0–60% between communities and from 19–33% between regions. Perforations of the tympanic membrane affected 40% of children in their first 18 months of life. These were not always persistent. Conclusion Overall, 1 in every 2 children examined had otoscopic signs consistent with suppurative ear disease and 1 in 4 children had a perforated tympanic membrane. Some of the children with intact tympanic membranes had experienced a perforation that healed before the survey. In this high-risk population, high rates of tympanic perforation were associated with high rates of bulging of the tympanic membrane.

Studies among men who have sex with men (MSM) in sub-Saharan Africa (SSA) focus mainly on HIV epidemiology, revealing little about the diversity within this population. We utilized data from the HIV Prevention Trials Network (HPTN) 075 study, to explore demographic and psychosexual characteristics of MSM in SSA who also have sex with women. Persons included in the analyses were aged 18-44 years and assigned male sex at birth and identified as male, reported anal sex with a man in the past 3 months, and had enrolled at one of four study sites (Kisumu, Kenya; Blantyre, Malawi; Cape Town and Soweto, South Africa). Nearly a quarter of the participants had recently engaged in sex with both men and women (MSMW). These men differed in terms of demographic and psychosexual characteristics, and sexual behavior from men who only had had sex with men (MSME). Compared to the latter, MSMW were more likely to prefer the insertive sexual role, reported more sexual partners in the past three months, and had more instances of condomless insertive anal intercourse with a man. These findings suggest that men who have sex with both men and women have specific characteristics and need tailored interventions that take their specific needs into account., Competing Interests: Declarations. Ethical Approval: This manuscript is published with the permission of the Director of KEMRI Center for Global Health Research. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the U.S. Centers for Disease Control and Prevention. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflict of Interest: The authors have no competing interests to report., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study explored interest in injectable PrEP (I-PrEP) and willingness to participate in clinical trials testing new biomedical HIV prevention strategies among men and transfeminine persons who have sex with men (MSM & TGP), using data collected in the HIV Prevention Trials Network (HPTN) 075 study, which took place at sites in Kenya, Malawi, and South Africa. Data result from a survey among 267 18-44 years old HIV negative participants, complemented with semi-structured interviews with 80 purposively recruited persons. Correlations coefficients were calculated to identify demographic and psychosocial factors associated with interest in I-PrEP. Qualitative interviews were analyzed using concept-driven and subsequent data-driven coding. Most surveyed participants expressed an interest in I-PrEP. Quantitatively, only being interested in other HIV prevention measures was associated with interest in I-PrEP. Qualitatively, most participants preferred I-PrEP to O-PrEP and remained interested in I-PrEP despite barriers such as the somewhat invasive nature of the procedure and potential side effects of I-PrEP. Interest in I-PrEP was driven by the possibility of avoiding sexual or HIV stigma. Access to healthcare and altruism-such as assisting in the development of new HIV prevention methods-positively impacted willingness to participate in clinical trials. With I-PrEP favored by most participants, it is potentially a critical tool to prevent HIV infection among MSM & TGP in sub-Saharan Africa, with the mitigation of stigma as a major advance. Recruitment of MSM & TGP in biobehavioral clinical trials seems feasible, with altruistic reasons and receiving I-PrEP and free medical care as major motivators., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Caesarean section (CS) rates are continuing to rise worldwide. Elective repeat CS (ERCS) greatly contribute to the rising rate which increases unnecessary risks of maternal and neonatal morbidity and mortality. Vaginal birth after caesarean (VBAC) is a safe mode of birth for most women; however, uptake remains low. Our objective is to find the factors that influence women's decision-making to support informed choices for the mode of next birth after caesarean section (NBAC)., Methods: A literature search was conducted in CINAHL, Maternity and Infant Care, Embase, EmCare, Cochrane Library and Medline databases. Primary, qualitative, peer reviewed, English language research articles were assessed according to inclusion/exclusion criteria. Articles were systematically assessed for inclusion or exclusion. Included studies were assessed using the Critical Appraisal Skills Programme qualitative studies checklist, Noblit and Hare's seven-step meta-ethnography approach synthesised themes., Results: Fourteen primary research articles were included. Six studies on 287 women focused on VBAC, and eight studies examined both VBAC and ERCS with 1861 women and 311 blogs. Thematic analysis yielded four primary themes: Influence of health professionals, impact of previous birth experience, optimal experience, and being in control., Conclusion: This meta-ethnography highlights health professionals' influence on women's decision making. To assist in decision-making, women need supportive health professionals who provide the current evidence-informed information about risks and benefits of each mode of birth. Health professionals need skills to provide supportive shared decision-making, debrief women regarding indications for their primary caesarean, and address issues of safety, fear, and expectations of childbirth., Competing Interests: None declared., (Copyright: © International Journal of Community Based Nursing and Midwifery.)

There remains a limited understanding of how men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA) perceive their risk for HIV and how risk influences behavior during sexual interactions. We performed thematic analysis on in-depth interviews from the qualitative sub-study of HPTN 075 in Kenya, Malawi, and South Africa. Using the Integrated Behavioral Model (IBM) constructs, we found that most MSM and TGW perceived themselves to be at risk for HIV, leading them to regularly engage in safer sexual behaviors. Notably, even though these MSM and TGW perceived themselves to be at risk for HIV, some of them reported engaging in transactional sex, sex under the influence of alcohol, and intentional non-use of condoms. This indicates that HIV risk perception was not always associated with safer sexual behaviors or a reduction in risk behaviors. Attitudes (negative attitudes toward condom use), perceived norms (social pressures), and environment constraints (contextual barriers) were related to MSM and TGW not engaging in safe sexual behavior. Hearing the perspectives of MSM and TGW on their sexual behavior continues to be important for the development and implementation of effective prevention policies and interventions. Eliminating structural barriers such as stigma, discrimination, and criminalization of same-sex sexuality is a crucial prerequisite for the success of interventions to promote sexual health among MSM and TGW in SSA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Mbilizi Chimwaza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adherence to care and antiretroviral therapy is challenging, especially for people living with HIV (PLWH) with additional co-occurring risk factors. Case management interventions, including motivational interviewing (MI), show promise to improve HIV treatment adherence, but few studies have examined how such interventions are delivered to or experienced by PLWH who have been reengaged in care. We conducted qualitative interviews with six case managers and 110 PLWH exiting from a randomized study (HPTN 078) who received a MI-based case management intervention in addition to standard patient-navigation services, or standard services only. Our study provided greater insight into the main findings from HPTN 078, including an in-depth description of the multiple barriers to adherence faced by this largely "out-of-care" population, as well as a more nuanced understanding of the benefits and challenges of implementing MI. A blend of MI plus more intensive interventions may be needed for PLWH facing multiple structural barriers., (© 2022. The Author(s).)

Background: The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TGW) from Kenya, Malawi, and South Africa. During the study follow-up, 21 participants acquired human immunodeficiency virus (HIV) (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection data among MSM and TGW enrolled in HPTN 075., Methods: HIV genotyping and drug resistance testing were performed for participants living with HIV who had viral loads >400 copies/mL at screening (prevalent cases, n = 124) and seroconverters (n = 21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by a longitudinal analysis of env and pol sequences generated by next-generation sequencing., Results: HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analyses identified 11 clusters (2-6 individuals). Clusters included seroconverters only (n = 1), prevalent cases and seroconverters (n = 4), and prevalent cases only (n = 6). Superinfections were identified in 1 prevalent case and 2 seroconverters. The annual incidence of superinfection was higher among seroconverters than among prevalent cases, and was higher than the rate of primary HIV infection in the cohort., Conclusions: This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TGW in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: People who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention., Methods: Participants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention., Results: The intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (<40 copies/mL) declined from 41% to 29% (estimated 9.4% decrease per year, 95% CI -17.0%; -1.8%). The in need of support group re-enrolled 94 participants and had increased ART (re-enrollment: 55%, week 26: 69%) and MOUD (re-enrollment: 16%, week 26: 25%) use, and viral suppression (re-enrollment: 40%, week 26: 49%)., Conclusions: Viral suppression declined in year 2 for those who initially received the HPTN 074 intervention and improved maintenance support is warranted. Viral suppression and MOUD increased among in need participants who received intervention during the study extension. Continued efforts are needed for widespread implementation of this scalable, integrated intervention., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: HPTN 075 enrolled men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa. Persons in HIV care or on antiretroviral treatment (ART) were not eligible to enroll. We evaluated antiretroviral (ARV) drug use, viral suppression, and drug resistance in this cohort over a 12-month follow-up period., Methods: Assessments included 64 participants with HIV (39 MSM, 24 TGW, and one gender not specified). ARV drugs were detected using a qualitative assay. Viral load (VL) and drug resistance testing were performed using commercial assays., Results: Over 12 months, the proportion of participants using ARV drugs increased from 28.1% to 59.4% and the proportion with VLs <400 copies/mL increased from 21.9% to 57.8%. The rate of ART failure (detection of drugs without viral suppression) was similar at screening and 12 months (12.0% and 11.1%, respectively) and was similar among MSM and TGW. Two participants developed HIV drug resistance during follow-up., Conclusions: Over 12 months, ARV drug use in the cohort more than doubled and viral suppression increased nearly threefold without a significant increase in ART failure or drug resistance. These results suggest that ART can be successfully scaled up for HIV prevention and treatment in this high-risk population., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Few studies have assessed HIV incidence in men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA). We assessed HIV incidence and its correlates among MSM and TGW in SSA enrolled in the prospective, multi-country HIV Prevention Trials Network (HPTN) 075 study, conducted from 2015 to 2017. Participants were enrolled at four sites in SSA (Kisumu, Kenya; Blantyre, Malawi; Cape Town and Soweto, South Africa). Eligible participants reported male sex assignment at birth, were 18 to 44 years of age, and had engaged in anal intercourse with a man in the preceding three months. Participation involved five study visits over 12 months. Visits included behavioral assessments and testing for HIV and sexually transmitted infections. Twenty-one of 329 persons acquired HIV during the study [incidence rate: 6.96/100 person-years (PY) (95% CI: 4.3, 10.6)]. Among TGW, HIV incidence was estimated to be 8.4/100 PY (95% CI: 2.3, 21.5). Four participants were found to have acute HIV infection at their first HIV-positive visit. HIV incidence varied among the four study sites, ranging from 1.3/100 PY to 14.4/100 PY. In multivariate longitudinal analysis, factors significantly associated with HIV acquisition were engagement in unprotected receptive anal intercourse [adjusted hazard ratio (AHR) 5.8, 95% confidence interval (CI): 2.4, 14.4] and incident rectal gonorrhea and/or chlamydia (AHR: 2.7, 95% CI: 1.1, 6.8). The higher HIV incidence in Cape Town compared to Blantyre could be explained by the higher prevalence of several risk factors for HIV infection among participants in Cape Town. Annual HIV incidence observed in this study is substantially higher than reported HIV incidence in the general populations in the respective countries and among MSM in the United States. Intensification of HIV prevention efforts for MSM and TGW in SSA is urgently needed., Competing Interests: The authors have declared that no competing interests exist.

Background: HIV Prevention Trials Network (HPTN) 074 evaluated human immunodeficiency virus (HIV) prevention interventions for people who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. Study interventions included support for HIV infection and substance use treatment. The study enrolled index participants living with HIV and injection partners who were not living with HIV. Seven partners acquired HIV infection during the study (seroconverters). We analyzed the phylogenetic relatedness between HIV strains in the cohort and the multiplicity of infection in seroconverters., Methods: Pol region consensus sequences were used for phylogenetic analysis. Data from next-generation sequencing (NGS, env region) were used to evaluate genetic linkage of HIV from the 7 seroconverters and the corresponding index participants (index-partner pairs), to analyze HIV from index participants in pol sequence clusters, and to analyze multiplicity of HIV infection., Results: Phylogenetic analysis of pol sequences from 445 index participants and 7 seroconverters identified 18 sequence clusters (2 index-partner pairs, 1 partner-partner pair, and 15 index-only groups with 2-7 indexes/cluster). Analysis of NGS data confirmed linkage for the 2 index-partner pairs, the partner-partner pair, and 11 of the 15 index-index clusters. The remaining 5 seroconverters had infections that were not linked to the corresponding enrolled index participant. Three (42.9%) of the 7 seroconverters were infected with more than 1 HIV strain (3-8 strains per person)., Conclusions: We identified complex patterns of HIV clustering and linkage among PWID in 3 communities. This should be considered when designing strategies for HIV prevention for PWID., Clinical Trials Registration: NCT02935296., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Opioid agonist treatment (OAT) is an effective method of addiction treatment and HIV prevention. However, globally, people who inject drugs (PWID) have insufficient OAT uptake. To expand OAT access and uptake, policymakers, program developers and healthcare providers should be aware of barriers to and facilitators of OAT uptake among PWID., Methods: As a part of the HPTN 074 study, which assessed the feasibility of an intervention to facilitate HIV treatment and OAT in PWID living with HIV in Indonesia, Ukraine, and Vietnam, we conducted in-depth interviews with 37 HIV-positive PWID and 25 healthcare providers to explore barriers to and facilitators of OAT uptake. All interviews were audio-recorded, transcribed, translated into English, and coded in NVivo for analysis. We developed matrices to identify emergent themes and patterns., Results: Despite some reported country-specific factors, PWID and healthcare providers at all geographic locations reported similar barriers to OAT initiation, such as complicated procedures to initiate OAT, problematic clinic access, lack of information on OAT, misconceptions about methadone, financial burden, and stigma toward PWID. However, while PWID reported fear of drug interaction (OAT and antiretroviral therapy), providers perceived that PWID prioritized drug use over caring for their health and hence were less motivated to take up ART and OAT. Motivation for a life change and social support were reported to be facilitators., Conclusion: These results highlight a need for support for PWID to initiate and retain in drug treatment. To expand OAT in all three countries, it is necessary to facilitate access and ensure low-threshold, financially affordable OAT programs for PWID, accompanied with supporting interventions. PWID attitudes and beliefs about OAT indicate the need for informational campaigns to counter misinformation and stigma associated with addiction and OAT (especially methadone).

The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13-21 years) in rural Mpumalanga Province, South Africa, during 2011-2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference = 3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect = 1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect = 1.5, 95% CI: -0.3, 3.3). All mediators jointly explained two-thirds (indirect effect = 2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Persons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment., Methods: HPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment., Results: Fifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm., Conclusions: In HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART., Competing Interests: We have read the journal's policy. None of the authors has a financial or personal relationship with other people or organizations that could inappropriately influence (bias) their work. Dr. Eshleman has collaborated on research studies with investigators from Abbott Diagnostics; Abbott Diagnostics provided reagents for some of those studies. Dr. Eshleman did not receive any funding or other support from Abbott Diagnostics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

We used antiretroviral (ARV) drug testing to evaluate the accuracy of self-reported data for HIV status and antiretroviral treatment (ART) among people who inject drugs enrolled in an HIV prevention trial. ARV drugs were detected in enrollment samples from 72/482 = 14.9% HIV-infected participants (39/52 = 75.0% who reported being on ART; 33/430 = 7.7% who reported not being on ART). Overall, 213/482 = 44.2% participants indicated that they were not aware of their HIV-positive status prior to study entry; of those, 30 had ARV drugs detected at enrollment, including 15 who also had ARV drugs detected at the screening visit. These participants were likely aware of their HIV-positive status at study entry but did not report this to study staff. This study shows that self-reported data on HIV testing history and ART may not be accurate and that ARV drug testing can help identify persons who are aware of their HIV-positive status and are on ART.

Throughout the world, men who have sex with men (MSM) are at increased risk for HIV infection compared to heterosexual men. Little is known about awareness of HIV infection and other gaps in the HIV care continuum for MSM, especially in sub-Saharan Africa (SSA). This information is urgently needed to address the HIV epidemic in this population. This study assessed gaps in the HIV care continuum among persons screened for participation in a multi-country prospective study that evaluated the feasibility of recruiting and retaining MSM for HIV prevention studies in SSA (HIV Prevention Trials Network (HPTN) 075, conducted in four cities in Kenya, Malawi, and South Africa). Participants were recruited using site-specific strategies, that included outreach and informal networks. Transgender women (TW) were eligible to participate. During screening, 601 MSM and TW were tested for HIV infection and asked about prior HIV testing, HIV status, engagement in care, and HIV treatment. Viral load testing and retrospective antiretroviral (ARV) drug testing were performed for HIV-infected participants. Most participants (92.2%) had a prior HIV test; 42.1% were last tested >6 months earlier. HIV prevalence was 30.4%. HIV infection was associated with older age and identifying as female or transgender; 43.7% of the HIV-infected participants were newly diagnosed, especially younger persons and persons with a less recent HIV test. Almost a third of previously-diagnosed participants were not linked to care. Most participants (88.7%) in care were on ARV treatment (ART). Only about one-quarter of all HIV-infected participants were virally suppressed. These findings demonstrate substantial prevalence of undiagnosed HIV infection and sub-optimal HIV care engagement among MSM and TW in SSA. Increased HIV testing frequency and better linkage to care represent critical steps in preventing further HIV transmission in this population. Once in care, gaps in the HIV care continuum appear less critical., Competing Interests: The authors have declared that no competing interests exist.

People who inject drugs (PWID) face barriers to engagement in antiretro-viral treatment (ART) and medication-assisted treatment (MAT). We detail the design, rapid preparation and adaptation, and systematic implementation of a flexible, individually tailored intervention for PWID in multiple settings: Indonesia, Ukraine, and Vietnam. HPTN 074 integrated systems navigation and counseling to facilitate entry and adherence to ART and MAT. Site-level guidance on the intervention involved in-depth interviews (IDIs) among PWID and their supporters and site-specific document review. IDIs emphasized ART misinformation and importance of social support for adherence. The document review revealed differences in health care system barriers, requiring an intervention that was flexible and tailored enough to address key outcomes. Implementation included regular debriefs for iterative adaptations based on participants' needs, including booster counseling sessions and subsidizing pre-ART testing. HPTN 074 provides a unique framework implementing a flexible and scalable intervention to improve ART and MAT outcomes among PWID across multiple settings.

Some HIV-infected individuals in research studies may choose not to disclose knowledge of their HIV status to study staff. We evaluated the accuracy of self-reported HIV status among African men and transgender women who have sex with men and who were screened for a research study. Sixty-seven of 183 HIV-infected participants reported a prior HIV diagnosis. Samples from the remaining 116 participants were tested for antiretroviral (ARV) drugs. Thirty-six of the 116 participants had ARV drugs detected, indicating that they were on antiretroviral treatment; these participants were classified as previously diagnosed based on ARV drug testing. Among participants classified as previously diagnosed, disclosure of a prior HIV diagnosis varied among study sites (p = 0.006) and was more common among those who reported having sex with men only (p = 0.002). ARV drug testing in addition to self-report improves the accuracy for identifying individuals with a prior HIV diagnosis.

The prevalence of intimate partner violence (IPV) is alarmingly high among South African adolescent girls and young women (AGYW). Limited data exist exploring how IPV prevalence and its risk factors differ by age. Study data were from the baseline visit of HPTN 068, a randomized controlled trial (RCT) conducted from 2011 to 2015 in Mpumalanga, South Africa. A cohort of 2,533 AGYW, aged 13 years to 20 years, answered survey questions on demographics and behaviors, including their experiences of physical and sexual violence ever and in the past 12 months. We calculated the prevalence of IPV and related risk factors, as well as prevalence ratios with 95% confidence intervals, stratified by age. Nearly one quarter (19.5%, 95% CI = [18.0, 21.2]) of AGYW experienced any IPV ever (physical or sexual) by a partner. The prevalence of any IPV ever among AGYW aged 13 years to 14 years, 15 years to 16 years, and 17 years to 20 years was 10.8%, 17.7%, and 32.1%, respectively. Key variables significantly associated with any IPV ever across all age groups included borrowing money from someone outside the home in the past 12 months, ever having had vaginal sex, ever having had anal sex, and consuming any alcohol. Few statistically significant associations were unique to specific age groups. The history of IPV among the youngest AGYW is a critical finding and should be a focus of prevention efforts., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The limiting antigen (LAg)-avidity assay is a serologic assay used for cross-sectional HIV incidence testing. We compared the results obtained with the LAg-avidity assay using dried blood spot (DBS) samples stored at room temperature (18°C-25°C) or stored frozen at -80°C with results obtained from matched plasma samples. Matched DBS and plasma samples (306 paired samples) were collected in the HIV Prevention Trials Network (HPTN) 068 trial in South Africa (2012-2014). The DBS were stored at room temperature before testing. Matched DBS and plasma samples (100 paired samples) from the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) were collected in 2016 and were stored at -80°C. All DBS testing was performed in 2017. Differences in normalized optical density (ODn) were compared between matched DBS and plasma samples. For DBS samples stored at room temperature (HPTN 068), the average difference in ODn values for plasma versus DBS was 1.49 (95% confidence intervals [CI]: 1.36-1.62). In contrast, when DBS samples were stored at -80°C (CEPHIA), the average difference in ODn values for plasma versus DBS was -0.22 (95% CI: -0.32 to -0.13). DBS samples stored at room temperature should not be used for cross-sectional HIV incidence testing with the LAg-avidity assay.

Background: Antiretroviral (ARV) drugs are used for HIV treatment and prevention. We analyzed ARV drug use and HIV drug resistance in a cohort of young women in rural South Africa enrolled in the HIV Prevention Trials Network (HPTN) 068 study, which evaluated the use of a cash transfer conditional on school attendance to reduce HIV incidence., Methods: ARV drug testing was performed using plasma samples from 2526 young women. This included 2526 enrollment samples (80 HIV-infected and 2446 HIV-uninfected) and 162 seroconversion samples (first HIV-positive study visit). Testing was performed using a qualitative assay that detects 20 ARV drugs from 5 drug classes. HIV drug resistance testing was performed with the ViroSeq HIV-1 Genotyping System for samples that had HIV viral loads ≥400 copies per milliliter., Results: At enrollment, ARV drugs were detected in 10 (12.5%) of 80 HIV-infected young women. None of 2446 HIV-uninfected young women had ARV drugs detected at enrollment. ARV drugs were also detected in 16 (9.9%) of 162 seroconverters. At enrollment, 9 (13.4%) of 67 young women with genotyping results had HIV drug resistance; resistance was also detected in 9 (6.9%) of 131 seroconverters with genotyping results., Conclusions: Most of the HIV-infected young women in this cohort from rural South Africa were not taking ARV drugs, suggesting they were unaware of their HIV status or were not in care. HIV drug resistance was detected in young women with both prevalent and new HIV infection.

Introduction: People who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV transmission and disease progression among PWID is essential in developing and effectively targeting intervention strategies of HIV treatment as prevention., Methods: We present a baseline analysis of HIV Prevention Trials Network (HPTN) 074, a two-arm, randomized controlled trial among PWID in Indonesia (n = 258), Ukraine (n = 457) and Vietnam (n = 439). HPTN 074 was designed to determine the feasibility, barriers and uptake of an integrated intervention combining health systems navigation and psychosocial counselling for the early engagement of antiretroviral therapy (ART) and substance use treatment for PWID living with HIV. Discordant PWID networks were enrolled, consisting of an HIV-positive index and their HIV-negative network injection partner(s). Among the enrolled cohort of 1154 participants (502 index participants and 652 network partners), we examine regional differences in the baseline risk structure, including sociodemographics, HIV and substance use treatment history, and injection and sexual risk behaviours., Results: The majority of participants were male (87%), with 82% of the enrolled females coming from Ukraine. The overall mean age was 34 (IQR: 30, 38). Most commonly injected substances included illegally manufactured methadone in Ukraine (84.2%), and heroin in Indonesia (81.8%) and Vietnam (99.5%). Injection network sizes varied by region: median number of people with whom participants self-reported injecting drugs was 3 (IQR: 2, 5) in Indonesia, 5 (IQR: 3, 10) in Ukraine and 3 (IQR: 2, 4) in Vietnam. Hazardous alcohol use, assessed using the Alcohol Use Disorders Identification Test - Alcohol Consumption Questions (AUDIT-C), was prominent in Ukraine (54.7%) and Vietnam (26.4%). Reported sexual risk behaviours in the past month, including having two or more sex partners and giving/receiving money or drugs in exchange for sex, were uncommon among all participants and regions., Conclusions: While regional differences in risk structure exist, PWID particularly in Ukraine need immediate attention for risk reduction strategies. Substantial regional differences in risk structure will require flexible, tailored treatment as prevention interventions for distinct PWID populations., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Some individuals control HIV replication without antiretroviral (ARV) therapy., Objective: To analyze viral suppression in young women in rural South Africa enrolled in a trial evaluating a behavioral intervention for HIV prevention., Methods: Plasma samples were obtained from women ages 13-24 (81 infected at enrollment, 164 seroconverters). ARV testing was performed using an assay that detects 20 ARV drugs. Women were classified as viremic controllers if they were virally suppressed for ≥12 months with no ARV drug use., Results: Samples from 216/245 (88.2%) women had no ARV drugs detected at their first HIV-positive visit. Thirty-four (15.7%) of the 216 women had a viral load <2,000 copies/mL. Fifteen of the 34 women were followed for ≥12 months; 12 were virally suppressed with no ARV drugs detected during follow-up. These women were classified as viremic controllers (overall: 12/216 = 5.6%). The median CD4 cell count at the first HIV-positive visit was higher among the 12 controllers than among the 204 women who were not using ARV drugs (759 vs. 549 cells/mm 3 , p = 0.02). Some women had a viral load <40 copies/mL at a single study visit, but none were classified as elite controllers (viral load <40 copies/mL for ≥12 months with no ARV drug use)., Conclusions: In this cohort, 5.6% of women who were not using ARV drugs had sustained viral suppression. This represents a minimum estimate of the frequency of viremic controllers in this cohort, since some women were not followed long enough to meet the criteria for classification.

Background: People who inject drugs (PWID) have a high incidence of HIV, little access to antiretroviral therapy (ART) and medication-assisted treatment (MAT), and high mortality. We aimed to assess the feasibility of a future controlled trial based on the incidence of HIV, enrolment, retention, and uptake of the intervention, and the efficacy of an integrated and flexible intervention on ART use, viral suppression, and MAT use., Methods: This randomised, controlled vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen, Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital site). PWID who were HIV infected (index participants) and non-infected injection partners were recruited as PWID network units and were eligible for screening if they were aged 18-45 years (updated to 18-60 years 8 months into study), and active injection drug users. Further eligibility criteria for index participants included a viral load of 1000 copies per mL or higher, willingness and ability to recruit at least one injection partner who would be willing to participate. Index participants were randomly assigned via a computer generated sequence accessed through a secure web portal (3:1) to standard of care or intervention, stratified by site. Masking of assignment was not possible due to the nature of intervention. The intervention comprised systems navigation, psychosocial counselling, and ART at any CD4 count. Local ART and MAT services were used. Participants were followed up for 12-24 months. The primary objective was to assess the feasibility of a future randomised controlled trial. To achieve this aim we looked at the following endpoints: HIV incidence among injection partners in the standard of care group, and enrolment and retention of HIV-infected PWID and their injection partners and the uptake of the integrated intervention. The study was also designed to assess the feasibility, barriers, and uptake of the integrated intervention. Endpoints were assessed in a modified intention-to-treat popualtion after exclusion of ineligible participants. This trial is registered on ClinicalTrials.gov, NCT02935296, and is active but not recruiting new participants., Findings: Between Feb 5, 2015, and June 3, 2016, 3343 potential index participants were screened, of whom 502 (15%) were eligible and enrolled. 1171 injection partners were referred, and 806 (69%) were eligible and enrolled. Index participants were randomly assigned to intervention (126 [25%]) and standard of care (376 [75%]) groups. At week 52, most living index participants (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self-reported ART use was higher among index participants in the intervention group than those in the standard of care group (probability ratio [PR] 1·7, 95% CI 1·4-1·9). Viral suppression was also higher in the intervention group than in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Index participants in the intervention group reported more MAT use at 52 weeks than those in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Seven incident HIV infections occurred, and all in injection partners in the standard of care group (intervention incidence 0·0 per 100 person-years, 95% CI 0·0-1·7; standard of care incidence 1·0 per 100 person-years, 95% CI 0·4-2·1; incidence rate difference -1·0 per 100 person-years, 95% CI -2·1 to 1·1). No severe adverse events due to the intervention were recorded., Interpretation: This vanguard study provides evidence that a flexible, scalable intervention increases ART and MAT use and reduces mortality among PWID. The low incidence of HIV in both groups impedes a future randomised, controlled trial, but given the strength of the effect of the intervention, its implementation among HIV-infected PWID should be considered., Funding: US National Institutes of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa., Methods: Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13-20 years (Mpumalanga province, 2011-2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software., Results: The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6-7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2-6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931-1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3-2.81x10-3) per site per year., Conclusions: Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial., Competing Interests: None of the authors has a conflict of interest or potential conflict of interest, with the following exceptions: Susan Eshleman has collaborated on research studies with investigators from Abbott Laboratories (distributor of the ViroSeq HIV-1 Genotyping System); Abbott Laboratories has provided reagents for other research studies. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To analyze antiretroviral drug use and HIV drug resistance among HIV-infected MSM and transgender women who were screened for participation in the HIV Prevention Trials Network 075 study., Methods: A qualitative assay was used to detect 20 antiretroviral drugs in five drug classes; this assay is based on liquid chromatography coupled with high-resolution accurate-mass mass spectrometry. HIV viral load testing was performed using the RealTime HIV-1 Viral Load Assay. HIV drug resistance testing was performed using the ViroSeq HIV-1 Genotyping System. Logistic regression was used to evaluate factors associated with study outcomes., Results: Antiretroviral drugs were detected in 63 (34.4%) of 183 participants who had confirmed HIV infection at screening; 11 (17.5%) of the 63 participants were not virally suppressed. Six (54.5%) of the 11 participants had drug-resistant HIV, including four who had multiclass resistance. Seven (63.6%) of the 11 were at risk of acquiring resistance to additional antiretroviral drugs. In multivariate model, antiretroviral drugs were more frequently detected in older participants, those recruited from Kisumu, Kenya, and those who reported ever having been in HIV care or on antiretroviral therapy (ART)., Conclusion: Most of HIV-infected persons screened for participation in HIV Prevention Trials Network 075 were not on ART, and many of those who were on ART were not virally suppressed. Many of those participants had drug-resistant HIV. These findings highlight the need for improved HIV care for African MSM and transgender women.

Most U.S. investigators in the HIV Prevention Trials Network (HPTN) have been of majority race/ethnicity and sexual orientation. Research participants, in contrast, have been disproportionately from racial/ethnic minorities and men who have sex with men (MSM), reflecting the U.S. epidemic. We initiated and subsequently evaluated the HPTN Scholars Program that mentors early career investigators from underrepresented minority groups. Scholars were affiliated with the HPTN for 12-18 months, mentored by a senior researcher to analyze HPTN study data. Participation in scientific committees, trainings, protocol teams, and advisory groups was facilitated, followed by evaluative exit surveys. Twenty-six trainees have produced 17 peer-reviewed articles to date. Research topics typically explored health disparities and HIV prevention among black and Hispanic MSM and at-risk black women. Most scholars (81% in the first five cohorts) continued HIV research after program completion. Alumni reported program-related career benefits and subsequent funding successes. Their feedback also suggested that we must improve the scholars' abilities to engage new research protocols that are developed within the network. Mentored engagement can nurture the professional development of young researchers from racial/ethnic and sexual minority communities. Minority scientists can benefit from training and mentoring within research consortia, whereas the network research benefits from perspectives of underrepresented minority scientists.

Little is known about HIV treatment optimism and risk behaviors among Black men who have sex with men (BMSM). Using longitudinal data from BMSM in the HPTN 061 study, we examined participants' self-reported comfort with having condomless sex due to optimistic beliefs regarding HIV treatment. We assessed correlates of treatment optimism and its association with subsequent risk behaviors for HIV acquisition or transmission using multivariable logistic regression with generalized estimating equations. Independent correlates of treatment optimism included age ≥35 years, annual household income <$20,000, depressive symptoms, high HIV conspiracy beliefs, problematic alcohol use, and previous HIV diagnosis. Treatment optimism was independently associated with subsequent condomless anal sex with a male partner of serodiscordant/unknown HIV status among HIV-infected men, but this association was not statistically significant among HIV-uninfected men. HIV providers should engage men in counseling conversations to assess and minimize willingness to have condomless sex that is rooted in optimistic treatment beliefs without knowledge of viral suppression.

Recent theoretical studies with alkali atoms A* excited to high Rydberg states predicted the existence of ultra-long-range molecular bound states. Such excited dimers have large electric dipole moments which, in combination with their long radiative lifetimes, make them excellent candidates for manipulation in applications. This Letter reports on experimental investigations of the self-broadening of Rb principal series lines, which revealed multiple satellites in the line wings. The positions of the satellites agree quantitatively with theoretically predicted minima in the excited long-range Rydberg states of Rb2.

To describe multiple interacting fragmentation continua, we develop a method in which the vibrational channel functions obey outgoing wave Siegert boundary conditions. This paper demonstrates the utility of the Siegert approach, which uses channel energy eigenvalues that possess a negative imaginary part. The electron scattering energy in each such channel is rotated upward, giving it an equal and opposite imaginary part. This permits a natural inclusion of vibrational continua without requiring them to appear as explicit channels in the scattering matrix. Calculations illustrate the application of this theory to photoionization, photodissociation, and dissociative recombination.

Earlier surveys in the Aleutian Trench southeast of Kodiak Island, Alaska, indicated that Kodiak Seamount had a flat top and was a tablemount or guyot. This seamount is of special significance because it has been supposed that its surface was eroded at the same time as those of a line of guyots to the southeast. If so, its present position in the axis of the Aleutian Trench indicates that the line of guyots was formed before the trench. A two-part survey in 1965 showed that Kodiak Seamount is not flat-topped, and should be eliminated from the category of guyots. Reflection profiling records indicate that the seamount was formed before the adjacent sediments were deposited, and that the small trough, or moat, on the south side is a depositional feature probably formed by a scouring effect or by the acceleration of turbidity currents around the base of the mount.