RESUMEN
BACKGROUND: Advances in biomedical HIV prevention will soon offer young women a choice of HIV prevention methods, including various pre-exposure prophylaxis (PrEP) modalities such as daily oral pills, dapivirine vaginal ring, and long-acting injectable agents. By understanding preferences for contraceptive methods, we may draw analogies for the HIV prevention needs of young women. The UChoose Study was an open-label randomised cross-over study designed to evaluate the acceptability and preference for several contraceptive options as a proxy for HIV prevention methods that use similar types of administration. The study enrolled healthy HIV uninfected young women aged 15 to 19 years. At enrolment, participants were randomly assigned to a contraceptive method for a period of 16 weeks in the form of monthly Nuvaring® (vaginal ring), daily combined oral contraceptive (daily pills), or bi-monthly injectable contraceptive (injectable). After 16 weeks, participants crossed over to another contraceptive method, and those who had received the injectable and the daily pills received the vaginal ring for another 16 weeks, whereas those who had received the vaginal ring were able to choose between the injectable and daily pills, to ensure that all participants tried the vaginal ring-the least familiar option to the study population. RESULTS: Thirty-three participants were purposively recruited to participate in seven focus group discussions (FGD) and completed a pre-survey for their assigned group. Our sample comprised 14 participants randomised to use of the vaginal ring and daily pills and 19 participants randomised to use of the vaginal ring and injectable. For most participants, their preferences for a prevention method were based primarily on their desire to avoid negative aspects of one method rather than their positive user experience with another method. Most participants expressed initial hesitancy for trying new contraception method products; however, a lack of familiarity was moderated by a strong interest in diverse user-controlled prevention methods. Participants valued methods that had infrequent dosing and simplified use requirements. The injection and vaginal ring were preferred over daily pills as a potential HIV prevention method. CONCLUSION: Expanding the availability of diverse products could provide adolescents with multiple choices in HIV prevention for the uninitiated. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02404038 ). Registered March 31, 2015-Registered.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Humanos , Femenino , Adolescente , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Sudáfrica/epidemiología , Estudios Cruzados , Anticoncepción/métodos , Profilaxis Pre-Exposición/métodos , Anticonceptivos/uso terapéutico , Fármacos Anti-VIH/uso terapéuticoRESUMEN
Background: Adolescents are a unique population with significant unmet health needs. They are often excluded from research that may benefit them as they are perceived as vulnerable and needing protection from research participation. For Research Ethics Committees, conflicting positions in statutes, regulations and ethical guidelines about who provides informed consent for adolescent involvement in health research can be a significant barrier to approving adolescent research. For researchers, the requirement for parental/guardian proxy consent or prolonged approval processes may potentially result in the exclusion of those adolescents most vulnerable and at risk, particularly if issues such as gender-based violence, gender identity, sexuality and sexual practices are in question. Objectives: To describe the challenges to adolescent research and suggest strategies to address these. Method: We consider the legal and ethical framework in South Africa regarding the consenting age for adolescents in research, outline the challenges and, using examples of best practices, suggest strategies to address the current conundrum. Results: We suggest three principles to guide Research Ethics Committees on their approach to reviewing health research involving adolescents. Strategies to develop ethically acceptable approaches to adolescent research and consent processes are described, which include community involvement. We elaborate on examples of nuanced approaches to adolescent research. Conclusion: The inclusion of adolescents in research is critical in informing appropriate and effective health services for this vulnerable population, whilst providing an opportunity to link them into care and services where relevant.
RESUMEN
BACKGROUND: HIV incidence among adolescents in southern Africa remains unacceptably high. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention but there are few data on its implementation among adolescents. We aimed to investigate the safety, feasibility, and acceptability of PrEP with oral tenofovir disoproxil fumarate and emtricitabine as part of a comprehensive HIV prevention package in an adolescent population in South Africa. METHODS: This open-label single-arm phase 2 study (PlusPills) was done in two research clinics in Cape Town and Johannesburg, South Africa. Adolescents aged 15-19 years were recruited into the study through recruitment events and outreach in the community. Potential participants were eligible for enrolment if they reported being sexually active. Exclusion criteria were a positive test for HIV or pregnancy at enrolment, breastfeeding, or any relevant co-morbidities. Participants were given oral tenofovir disoproxil fumarate and emtricitabine for PrEP to take daily for the first 12 weeks and were then given the choice to opt in or out of PrEP use at three monthly intervals during scheduled clinic visits. Participants were invited to monthly visits for adherence counselling and HIV testing during the study period. The primary outcomes were acceptability, use, and safety of PrEP. Acceptability was measured by the proportion of participants who reported willingness to take up PrEP and remain on PrEP at each study timepoint. Use was defined as the number of participants who continued to use PrEP after the initial 12-week period until the end of the study (week 48). Safety was measured by grade 2, 3, and 4 laboratory and clinical adverse events using the Division of AIDS table for grading the severity of adult and paediatric adverse events, version 1.0. Dried blood spot samples were collected at each study time-point to measure tenofovir diphosphate concentrations. This trial is registered with ClinicalTrials.gov, NCT02213328. FINDINGS: Between April 28, 2015, and Nov 11, 2016, 244 participants were screened, and 148 participants were enrolled (median age was 18 years; 99 participants [67%] were female) and initiated PrEP. PrEP was stopped by 26 of the 148 (18%) participants at 12 weeks. Cumulative PrEP opt-out, from the total cohort, was 41% (60 of 148 participants) at week 24 and 43% (63 of 148 participants) at week 36. PrEP was well tolerated with only minor adverse events (grade 2) thought to be related to study drug, which included headache (n=4, 3%), gastrointestinal upset (n=8, 5%), and skin rash (n=2, 1%). Two participants (1%) experienced grade 3 weight loss, which was deemed related to the study drug and resolved fully when PrEP was discontinued. Tenofovir diphosphate concentrations were detectable (>16 fmol/punch) in dried blood spot samples in 108 (92%) of 118 participants who reported PrEP use at week 12, in 74 (74%) of 100 participants at week 24, and in 22 (59%) of 37 participants by the study end at week 48. INTERPRETATION: In this cohort of self-selected South African adolescents at risk of HIV acquisition, PrEP appears safe and tolerable in those who continued use. PrEP use decreased throughout the course of the study as the number of planned study visits declined. Adolescents in southern Africa needs access to PrEP with tailored adherence support and possibly the option for more frequent and flexible visit schedules. FUNDING: National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Emtricitabina/administración & dosificación , Infecciones por VIH/prevención & control , Tenofovir/administración & dosificación , Adolescente , Adulto , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Profilaxis Pre-Exposición/métodos , Sudáfrica , Adulto JovenRESUMEN
INTRODUCTION: Young women in Southern Africa have extremely high HIV incidence rates necessitating the availability of female-controlled prevention methods. Understanding adolescent preference for seeking contraception would improve our understanding of acceptability, feasibility and adherence to similar modes of delivery for HIV prevention. METHODS: UChoose was an open-label randomized crossover study over 32 weeks which aimed to evaluate the acceptability and preference for contraceptive options in healthy, HIV-uninfected, female adolescents aged 15 to 19 years, as a proxy for similar HIV prevention methods. Participants were assigned to a contraceptive method for a period of 16 weeks in the form of a bi-monthly injectable contraceptive, monthly vaginal Nuvaring® or daily combined oral contraceptive (COC) and then asked to state their preference. At 16 weeks, participants crossed over to another contraceptive method, to ensure that all participants tried the Nuvaring® (least familiar modality) and additionally, either the injection or COC. Primary outcomes were contraceptive acceptability and preference. At the end of the 32 weeks they were also asked to imagine their preference for an HIV prevention modality. Secondary endpoints included changes in sexual behaviour, contraceptive adherence and preference for biomedical and behavioural HIV prevention methods. RESULTS: Of the 180 participants screened, 130 were enrolled and randomized to the Nuvaring® (n = 45), injection (n = 45) or COC (n = 40). Significantly more Nuvaring® users (24/116; 20.7%) requested to change to another contraceptive option compared to injection (1/73; 1.4% p = 0.0002) and COC users (4/49; 8% p = 0.074). Of those that remained on the Nuvaring® , adherence was significantly higher than to COC (p < 0.0001). Significantly more injection users (77/80; 96.3%) thought this delivery mode was convenient to use compared to Nuvaring® (74/89; 83.1%; p = 0.0409) or COC (38/50; 76.0%; p = 0.0034). Overall, the preferred contraceptive choice was injection, followed by the ring and lastly the pill. CONCLUSIONS: Adherence to daily COC was difficult for adolescents in this cohort and the least favoured potential HIV prevention option. While some preferred vaginal ring use, these data suggest that long-acting injectables would be the preferred prevention method for adolescent girls and young women. This study highlights the need for additional options for HIV prevention in youth.
Asunto(s)
Agentes Anticonceptivos Hormonales/administración & dosificación , Dispositivos Anticonceptivos Femeninos , Anticonceptivos Orales Combinados/administración & dosificación , Desogestrel/análogos & derivados , Etinilestradiol , Infecciones por VIH/prevención & control , Administración Intravaginal , Adolescente , África Austral , Estudios Cruzados , Combinación de Medicamentos , Femenino , Humanos , Inyecciones Intramusculares , Prioridad del Paciente , Satisfacción del Paciente , Sudáfrica , Adulto JovenRESUMEN
BACKGROUND: Midwives provide care to women across the childbearing journey from pre-conception to the post-partum period in various clinical settings. Due to the increasing incidence of diabetic pregnancies, midwives are now in a position to support other health professionals, as part of a team, to reduce the stress and / or demand on the health care services. OBJECTIVE: This integrative review synthesises original research that explores the experiences and perceptions of midwives in the provision of care for women with diabetes. DESIGN: Integrative review. METHODS: Whittemore and Knafl's (2005) systematic approach was used to search for primary literature related to the research question. Studies meeting the following criteria were included: primary qualitative, quantitative and mixed methods research studies published in peer reviewed journals between January 2009 to October 2019. The population of interest being midwives or nurse-midwives and the outcomes of interest included their perceived role in the management of women with diabetes from the pre conceptual to the postpartum period. The methodological quality of the studies was assessed using the appropriate CASP (Critical Appraisal Skills Programmes, 2014) criteria for qualitative and quantitative research studies. A robust search strategy was conducted using the following databases: EBCSO host (all data bases), Embase, Scopus, and Science Direct (see Table 1). FINDINGS: A total of 7275 articles were retrieved and ten papers were included in this review (five qualitative and five quantitative) that fulfilled the inclusion criteria. Two overarching themes were identified: professional and personal impacts on midwifery practice. The professional impact theme included three sub themes: organisational issues, professional development and holistic support. The personal impact theme also included three themes: limited diabetes knowledge, limited clinical practice skills and mental attitude. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The findings indicate that midwives need opportunities to learn and develop skills specific to their role so that each individual's needs can be met. These opportunities include provision of education at a university level, offering work based training and increasing the number of post registration courses targeted at midwives who are willing to upskill to provide appropriate care to women with diabetes. Courses are required to address the knowledge, attitudes to diabetes, appropriate assessment skills and innovative communication skills for midwives.
Asunto(s)
Diabetes Mellitus/terapia , Acontecimientos que Cambian la Vida , Partería/normas , Adulto , Diabetes Mellitus/psicología , Femenino , Humanos , Partería/tendencias , Noruega , Embarazo , Investigación CualitativaAsunto(s)
Investigación Biomédica/normas , Prestación Integrada de Atención de Salud/normas , Países en Desarrollo/estadística & datos numéricos , Neoplasias de Cabeza y Cuello/prevención & control , Necesidades y Demandas de Servicios de Salud/normas , Proyectos de Investigación/normas , África/epidemiología , Neoplasias de Cabeza y Cuello/epidemiología , Humanos , Encuestas y CuestionariosRESUMEN
Sun protection behavior studies are almost exclusively carried out in populations with fair skin for the obvious reason that people with unpigmented skin are more susceptible to the health impacts of excess solar ultraviolet radiation exposure. In a dataset of 1271 Black South Africans, we analyzed factors related to sun protection applied when spending time outdoors including awareness of skin cancer, gender, age and Living Standards Measure (LSM) where 1-4 equate to the lowest, 5-7 intermediate and 8-10 the highest LSM status. The most important driver for Black South Africans to use sun protection was whether they were aware of skin cancer (OR: 2.6 for those who were aware versus those who were not, P < 0.0001). Sunscreen was preferred by respondents in LSM 8-10 whereas people in the lowest group (LSM 1-4) favored shade, umbrellas and hats. One in two respondents claimed to use some form of sun protection, which appears to be higher than deeply pigmented populations in other countries.
Asunto(s)
Población Negra , Conductas Relacionadas con la Salud , Protectores Solares/administración & dosificación , Adulto , Femenino , Humanos , Masculino , Sudáfrica , Luz SolarRESUMEN
Little is known about levels of awareness and perceptions of skin cancer among Africans living in Africa. This study assessed skin cancer awareness among 1271 deeply pigmented South Africans. Participants (n = 642 males vs n = 629 females) were aware of skin cancer (79%) with more females than males being aware of skin cancer (P = 0.02). Majority of all participants had never checked their skin for signs or symptoms of skin cancer (90%). Palms of hands and soles of feet were the least recognized anatomic sites for skin cancer development, despite these sites being the common sites for acral lentiginous melanoma in individuals with deeply pigmented skin. Results suggest a need for targeted skin cancer awareness among population groups with dark skin on identification, screening, and early detection, professional training for healthcare personnel and content on skin cancer in deeply pigmented skin in medical curricula.
Asunto(s)
Concienciación , Población Negra , Neoplasias Cutáneas/epidemiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sudáfrica/epidemiologíaRESUMEN
BACKGROUND: We assessed the effect on the torsional stability by different pin diameters and varied pin configurations in a biomechanical supracondylar humerus fracture model. METHODS: After scanning a model of a pediatric humerus, the image was imported into software. Variable pin trajectories were planned. Acrylonitrile butadiene styrene plastic models were 3-dimensionally printed with predetermined pin trajectories. Models were osteotomized and potted with a polyurethane resin. Five-pin configurations were designed to test coronal and sagittal patterns of pin placement. Each included 3 lateral pins and a medial pin. Pin diameters of 1.6, 2.0, and 2.4 mm were tested in all configurations. Three models for each pin diameter/configuration were tested to ensure uniformity. Stability of the construct was tested to determine the torque needed to deflect the osteotomy 10 degrees in internal/external rotation. Each model was tested 3 times. RESULTS: In all models/configurations, the 2.4 mm pin diameter was statistically stiffer than 1.6 mm diameter pins; this lost statistical significance in certain patterns when comparing 2.0- and 2.4-mm pins. When comparing a divergent to a parallel configuration in the coronal plane, there was no significant difference in stability when pin diameter or number were controlled. The convergent pin configuration was, in general, the least stable pattern. Use of a medial pin conferred statistically significant stiffness throughout most models as demonstrated with pin deletion. Use of 2 pins was significantly less stiff than most 3-pin models. CONCLUSIONS: Larger pin diameters confer greater stiffness among all patterns. The use of 3 lateral and 1 medial pin was not statistically different than 2 lateral and 1 medial pin in our models. Both patterns were stiffer than 3 lateral pins only or other fewer pin constructs. The alignment of pins in the sagittal plane did not affect overall construct stiffness.
Asunto(s)
Fenómenos Biomecánicos/fisiología , Clavos Ortopédicos , Fijación Interna de Fracturas , Fracturas del Húmero , Húmero/cirugía , Clavos Ortopédicos/efectos adversos , Clavos Ortopédicos/normas , Niño , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Humanos , Fracturas del Húmero/fisiopatología , Fracturas del Húmero/cirugía , Modelos Anatómicos , Impresión Tridimensional , Diseño de Prótesis , TorqueRESUMEN
The Human Research Council's National HIV Prevalence, Incidence and Behavior Survey ranks South Africa first in HIV incidence in the world with 400,000 new infections in 2012 and found the HIV incidence rate among female youth aged 15 to 24 years to be 2.5% that year. The objective of this study was to compare the pattern and predictability of sexual activity between HIV-infected and HIV-uninfected young South African women. Sexually active young women between the ages of 16 and 21 years old completed a study survey between October 2012 and 2014 at two Desmond Tutu HIV Foundation centers. 100 young women with a mean age of 19.04 years responded to the survey. 51 women (51%) were HIV-infected and 49 were HIV-uninfected (49%). HIV-infected young women were found to be statistically less likely to have a temporal pattern to their sexual activity as compared to HIV-uninfected young women (56.9 vs. 95.9%, p<0.0001). While controlling for frequency of sex and lifetime sexual partners, HIV status remains a significant predictor of having a pattern of sexual activity (OR=16.13, p=0.0004) and a predictor of having sex on the weekend only (OR=4.41, p=0.0022). The ability to predict when sexual activity will occur enables a woman to prepare for its associated risks. HIV-uninfected young women are more likely to have a predictable pattern to their sexual activity as compared to HIV-infected young women. Knowledge of the sexual behavior patterns of this high-risk population will aid in the development of effective HIV prevention campaigns.
RESUMEN
BACKGROUND: New biomedical prevention technologies (NPTs) may contribute to substantially reducing incident HIV infections globally. We explored acceptability and preferences for NPTs among key and other vulnerable populations in two South African townships. METHODS: We conducted six focus groups and 12 in-depth interviews with adolescents, and adult heterosexual men, women, and men who have sex with men (MSM) (n = 48), and eight in-depth interviews with key informant healthcare workers. The interview guide described pre-exposure prophylaxis (PrEP), vaginal rings, rectal microbicides and HIV vaccines, and explored acceptability and product preferences. Focus groups and in-depth interviews (45-80 minutes) were conducted in Xhosa, audiotaped, and transcribed and translated into English. Data were coded and reviewed using framework analysis with NVivo software. RESULTS: Overall, initial enthusiasm and willingness to use NPTs evolved into concerns about how particular NPTs might affect or require alterations in one's everyday lifestyle and practices. Different product preferences and motivations emerged by population based on similarity to existing practices and contexts of vulnerability. Adult women and female adolescents preferred a vaginal ring and HIV vaccine, motivated by longer duration of protection to mitigate feared repercussions from male partners, including threats to their marriage and safety, and a context of ubiquitous rape. Male adolescents preferred an HIV vaccine, seen as protection in serodiscordant relationships and convenient in obviating the HIV stigma and cost involved in buying condoms. Adult men preferred PrEP, given familiarity with oral medications and mistrust of injections, seen as enabling serodiscordant couples to have a child. MSM preferred a rectal microbicide given familiarity with gel-based lubricants, with concerns about duration of protection in the context of unplanned consensual sex and rape. CONCLUSIONS: Biomedical interventions to prevent HIV transmission, rather than obviating social-structural factors that produce vulnerability, may be limited by these same factors. Implementation of NPTs should engage local communities to understand real-world constraints and strategise to deliver effective, multi-level combination prevention.
Asunto(s)
Infecciones por VIH/prevención & control , Aceptación de la Atención de Salud , Adolescente , Femenino , Grupos Focales , Homosexualidad Masculina , Humanos , Entrevistas como Asunto , Masculino , Profilaxis Pre-Exposición/métodos , Investigación Cualitativa , Conducta Sexual , SudáfricaRESUMEN
Placebo-controlled trials of pre-exposure prophylaxis (PrEP) have reported challenges with study-product uptake and use, with the greatest challenges reported in studies with young women in sub-Saharan Africa. We conducted a qualitative sub-study to explore experiences with open-label PrEP among young women in Cape Town, South Africa participating in HTPN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT). HPTN 067/ADAPT provided open label oral FTC/TDF PrEP to young women in Cape Town, South Africa who were randomized to daily and non-daily PrEP regimens. Following completion of study participation, women were invited into a qualitative sub-study including focus groups and in-depth interviews. Interviews and groups followed a semi-structured guide, were recorded, transcribed, and translated to English from isiXhosa, and coded using framework analysis. Sixty of the 179 women enrolled in HPTN 067/ADAPT participated in either a focus group (six groups for a total of 42 participants) or an in-depth interview (n = 18). This sample of mostly young, unmarried women identified facilitators of and barriers to PrEP use, as well as factors influencing study participation. Cross-cutting themes characterizing discourse suggested that women placed high value on contributing to the well-being of one's community (Ubuntu), experienced a degree of skepticism towards PrEP and the study more generally, and reported a wide range of approaches towards PrEP (ranging from active avoidance to high levels of persistence and adherence). A Mutuality Framework is proposed that identifies four dynamics (distrust, uncertainty, alignment, and mutuality) that represent distinct interactions between self, community and study and serve to contextualize women's experiences. Implications for better understanding PrEP use, and non-use, and intervention opportunities are discussed. In this sample of women, PrEP use in the context of an open-label research trial was heavily influenced by underlying beliefs about safety, reciprocity of contributions to community, and trust in transparency and integrity of the research. Greater attention to factors positioning women in the different dynamics of the proposed Mutuality Framework could direct intervention approaches in clinical trials, as well as open-label PrEP scale-up.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/prevención & control , Cumplimiento de la Medicación , Aceptación de la Atención de Salud/psicología , Profilaxis Pre-Exposición/métodos , Estigma Social , Adulto , Femenino , Grupos Focales , Humanos , Entrevistas como Asunto , Evaluación de Programas y Proyectos de Salud , Investigación Cualitativa , Sudáfrica , Adulto JovenRESUMEN
BACKGROUND: The first generation of South African (SA) children perinatally infected with HIV is entering adulthood, and there is now a pressing need for systematised transfer of these patients from paediatric to adult care. OBJECTIVES: Previous research has investigated the HIV healthcare transition in North America and Europe, yet none has been conducted in SA. Our study is the first to describe the perspectives of healthcare providers overseeing the transition in resource-limited settings. METHODS: We approached healthcare providers working in government paediatric HIV clinics and hospitals in the Western Cape Province, SA. Seven physicians and counsellors in adolescent/paediatric care, representing five clinics, were interviewed, and 43 completed a written survey. Interviews addressed the current state of the transition, barriers and facilitators, and model components. Interviews were assessed for major themes using framework analysis, while logistic regression was applied to survey responses to identify associations with measured covariates. RESULTS: Analysis of interview transcripts revealed several overarching perspectives that were corroborated by survey responses. One barrier identified was the healthcare providers' difficulty in letting go of their relationships with the adolescent patients. Since healthcare providers regarded their patients as particularly vulnerable, they felt a strong and protective attachment towards them. A second barrier identified was a lack of structure and effective communication between adult and paediatric providers; accordingly, healthcare providers feared that they were transferring their adolescents unprepared, to a judgemental, depersonalised and overburdened environment. All interviewees and a majority of survey respondents (>80%) agreed that the formation of adolescent support groups in adult care clinics as well as a later transition age would improve the transition process. CONCLUSION: This study highlights the need for a systematic healthcare transition for HIV-positive adolescents cared for in the Western Cape, while acknowledging the limitations of the current healthcare infrastructure. Several feasible recommendations have been identified, including forming support groups and greater involvement of adolescent healthcare providers to facilitate the transition.
RESUMEN
Breast cancer subtyping, based on the expression of hormone receptors and other genes, can determine patient prognosis and potential options for targeted therapy. Among breast cancer subtypes, tumors of basal-like and claudin-low subtypes are typically associated with worse patient outcomes, are primarily classified as triple-negative breast cancers (TNBC), and cannot be treated with existing hormone-receptor-targeted therapies. Understanding the molecular basis of these subtypes will lead to the development of more effective treatment options for TNBC. In this study, we focus on retinoic acid receptor responder 1 (RARRES1) as a paradigm to determine if breast cancer subtype dictates protein function and gene expression regulation. Patient tumor dataset analysis and gene expression studies of a 26 cell-line panel, representing the five breast cancer subtypes, demonstrate that RARRES1 expression is greatest in basal-like TNBCs. Cell proliferation and tumor growth assays reveal that RARRES1 is a tumor suppressor in TNBC. Furthermore, gene expression studies, Illumina HumanMethylation450 arrays, and chromatin immunoprecipitation demonstrate that expression of RARRES1 is retained in basal-like breast cancers due to hypomethylation of the promoter. Additionally, expression of the cancer stem cell marker, aldehyde dehydrogenase 1A3, which provides the required ligand (retinoic acid) for RARRES1 transcription, is also specific to the basal-like subtype. We functionally demonstrate that the combination of promoter methylation and retinoic acid signaling dictates expression of tumor suppressor RARRES1 in a subtype-specific manner. These findings provide a precedent for a therapeutically-inducible tumor suppressor and suggest novel avenues of therapeutic intervention for patients with basal-like breast cancer.
Asunto(s)
Aldehído Oxidorreductasas/genética , Neoplasias de la Mama/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/genética , Aldehído Oxidorreductasas/metabolismo , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Proteínas de la Membrana/metabolismo , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Pronóstico , Mapas de Interacción de Proteínas/genética , Interferencia de ARN , Trasplante Heterólogo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Carga Tumoral/genéticaRESUMEN
Infection with HIV is known to increase the risk of cervical cancer. In addition, evidence suggests that concurrent infection with multiple human papillomavirus (HPV) genotypes increases the risk of cervical dysplasia more than infection with a single HPV genotype. However, the impact of the combination of HIV coinfection and presence of multiple concurrent HPV infections on the risk of cervical dysplasia is uncertain. We compared the results of HPV testing and Pap smears between HIV-infected and HIV-uninfected young women to assess the cumulative impact of these two conditions. We found that both HIV and the presence of multiple concurrent HPV infections are associated with increased risk of associated Pap smear abnormality and that the impact of these two risk factors may be additive.
RESUMEN
Introduction: Since HIV testing in South African adolescents and young adults is sub-optimal, the objective of the current study was to investigate the feasibility and acceptability of an HIV rapid self-testing device in adolescents and young people at the Desmond Tutu HIV Foundation Youth Centre and Mobile Clinic. Methods: Self-presenting adolescents and young adults were invited to participate in a study investigating the fidelity, usability and acceptability of the AtomoRapid HIV Rapid self-testing device. Trained healthcare workers trained participants to use the device before the participant conducted the HIV self-test with device usage instructions. The healthcare worker then conducted a questionnaire-based survey to assess outcomes. Results: Of the 224 enrolled participants between 16 and 24 years of age, 155 (69,2%) were female. Overall, fidelity was high; 216 (96,4%) participants correctly completed the test and correctly read and interpreted the HIV test result. There were eight (3,6%) user errors overall; six participants failed to prick their finger even though the lancet fired correctly. There were two user errors where participants failed to use the capillary tube correctly. Participants rated acceptability and usability highly, with debut testers giving significantly higher ratings for both. Younger participants gave significantly higher ratings of acceptability. Conclusions: Adolescents and young adults found HIV self-testing highly acceptable with the AtomoRapid and they used the device accurately. Further research should investigate how, where and when to deploy HIV self-testing as a means to accompany existing strategies in reaching the UNAIDS goal to test 90% of all individuals worldwide.
RESUMEN
Background. The first generation of South African (SA) children perinatally infected with HIV is entering adulthood; and there is now a pressing need for systematised transfer of these patients from paediatric to adult care.Objectives. Previous research has investigated the HIV healthcare transition in North America and Europe; yet none has been conducted in SA. Our study is the first to describe the perspectives of healthcare providers overseeing the transition in resource-limited settings.Methods. We approached healthcare providers working in government paediatric HIV clinics and hospitals in the Western Cape Province; SA. Seven physicians and counsellors in adolescent/paediatric care; representing five clinics; were interviewed; and 43 completed a written survey. Interviews addressed the current state of the transition; barriers and facilitators; and model components. Interviews were assessed for major themes using framework analysis; while logistic regression was applied to survey responses to identify associations with measured covariates.Results. Analysis of interview transcripts revealed several overarching perspectives that were corroborated by survey responses. One barrier identified was the healthcare providers' difficulty in letting go of their relationships with the adolescent patients. Since healthcare providers regarded their patients as particularly vulnerable; they felt a strong and protective attachment towards them. A second barrier identified was a lack of structure and effective communication between adult and paediatric providers; accordingly; healthcare providers feared that they were transferring their adolescents unprepared; to a judgemental; depersonalised and overburdened environment. All interviewees and a majority of survey respondents (80%) agreed that the formation of adolescent support groups in adult care clinics as well as a later transition age would improve the transition process.Conclusion. This study highlights the need for a systematic healthcare transition for HIV-positive adolescents cared for in the Western Cape; while acknowledging the limitations of the current healthcare infrastructure. Several feasible recommendations have been identified; including forming support groups and greater involvement of adolescent healthcare providers to facilitate the transition
Asunto(s)
Adolescente , Adulto , Infecciones por VIH , Personal de Salud , Transición a la Atención de AdultosRESUMEN
Adolescents and young adults are at increased risk for HIV due to the many developmental, psychological, social, and structural transitions that converge in this period of the lifespan. In addition, adolescent deaths resulting from HIV continue to rise despite declines in other age groups. There are also young key populations (YKPs) that bear disproportionate burdens of HIV and are the most vulnerable, including young men who have sex with men (MSM), transgender youth, young people who inject drugs, and adolescent and young adult sex workers. As a society, we must do more to stop new HIV infections and untimely HIV-related deaths through both primary and secondary prevention and better management approaches. Using an interwoven prevention and treatment cascade approach, the starting point for all interventions must be HIV counselling and testing. Subsequent interventions for both HIV-negative and HIV-positive youth must be "adolescent-centred," occur within the socio-ecological context of young people and take advantage of the innovations and technologies that youth have easily incorporated into their daily lives. In order to achieve the global goals of zero infections, zero discrimination and zero deaths, a sustained focus on HIV research, policy and advocacy for YKPs must occur.
Asunto(s)
Infecciones por VIH/prevención & control , Adolescente , Adulto , Femenino , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Humanos , Masculino , Trabajadores Sexuales , Abuso de Sustancias por Vía Intravenosa/complicaciones , Personas Transgénero , Adulto JovenRESUMEN
HIV vaccine trials (HVTs) are ethically complex, and sound informed consent processes should facilitate optimal decision-making for participants. This study aimed to explore representations of critical HVT-related concepts to enhance the consent process. Four focus group discussions were conducted with participants from key constituencies at a South African HVT site. Thematic analysis was employed to identify representations of key HVT-related concepts. The findings suggest that (potential) participants may negotiate multiple, competing versions of HVT-related concepts in a somewhat unrecognized process, which may have significant implications for the consent process. Stakeholders involved in consent and engagement activities at sites should be assisted to elicit, engage, and resolve competing representations of HVT-related concepts. More empirical research is needed to explore how such stakeholders address competing representations in their interactions with potential participants.