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Adolescents living with HIV (ALWH) are particularly susceptible to disruptions in care, which may lead to poor HIV-related health outcomes. Here, we report the results of a longitudinal phone-based study investigating impacts of the COVID-19 pandemic on ALWH in New York City. Participants (N = 10, mean age 21.2 years, 50% female) demonstrated substantial COVID-19 knowledge and identified Instagram as their primary source of COVID-19 information. Nearly all participants reported loss of income, and 50% reported experiencing food insecurity as a result of the pandemic. These findings highlight existing vulnerabilities among ALWH that may threaten the continuum of care.
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COVID-19 , Infecções por HIV , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Masculino , Infecções por HIV/epidemiologia , Pandemias , Cidade de Nova Iorque , Estudos LongitudinaisRESUMO
ABSTRACTHIV stigma is associated with delayed HIV disclosure and worse clinical outcomes for adolescents living with HIV (ALWH). Teachers critically influence school environments, but are understudied in terms of HIV stigma. We implemented a school-level, cluster-randomized trial to assess the impact of a one-day multi-media training on the knowledge, attitudes and beliefs (K/A/B) of school teachers in western Kenya. Teachers' K/A/B were evaluated at baseline and six months. Additionally, we assessed stigma with ALWH enrolled in the included schools to explore the impact of the training. Teachers (N = 311) and ALWH (N = 19) were enrolled from 10 primary and 10 secondary schools. The intervention and control groups did not significantly differ in overall stigma score (mean 1.83 vs. 1.84; adjusted difference, 0.18 [95% CI, -0.082 to 0.045]) at six months; however, we found a trend towards improvement in overall stigma score and a significant difference in the community discrimination sub-scale among secondary school teachers (mean 3.02 vs. 3.19; adjusted difference, -0.166 [95% CI, -0.310 to -0.022]). ALWH reported few experiences of discrimination, but emphasized keeping their HIV status secret (84%). The teacher-training reduced secondary school teacher perceptions of community-level stigma, but did not impact individual attitudes or beliefs..
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Infecções por HIV , Capacitação de Professores , Adolescente , Humanos , HIV , Quênia , Professores Escolares , Instituições AcadêmicasRESUMO
Mobile technologies represent potentially novel and scalable intervention delivery platforms for adolescents living with HIV (ALWH) in low- and middle-income countries. We conducted a prospective, mixed methods pilot study to evaluate the acceptability and feasibility of the WhatsApp® platform to deliver individual counseling services and facilitate peer support for ALWH in western Kenya. Thirty ALWH (17 female, mean age 15.4) on ART, engaged in HIV care and aware of their status, were enrolled. After 6 months, participants described their experiences with the intervention. Treatment adherence, stigma, and mental and behavioral health were assessed prospectively. Participants reported overall positive experiences and indicated that the platform encouraged peer network development. They endorsed potential benefits for treatment adherence, stigma reduction, and mental and behavioral health. All participants supported intervention expansion. In western Kenya, WhatsApp® was an acceptable and feasible platform for mobile counseling and peer support for ALWH.
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Infecções por HIV , Saúde Mental , Adolescente , Feminino , Infecções por HIV/terapia , Humanos , Quênia , Projetos Piloto , Estudos ProspectivosRESUMO
HIV/AIDS-related stigma (HIV stigma) affects every aspect of adolescents' HIV management. Adolescents living with HIV (ALWH) are particularly vulnerable in schools where they have described experiencing HIV stigma. Teachers play a significant role in their students' lives. Stigmatizing attitudes or behaviors by teachers not only impact ALWH directly, but may influence the attitudes and behaviors of their peers. There is a dearth of literature exploring interventions to address HIV stigma in school-based settings. The objective of this review is to examine interventions to reduce HIV stigma among teachers globally. To conduct this systematic review, we used the PRISMA guidelines. Two articles met the inclusion criteria. Both eligible studies aimed to reduce HIV stigma among teachers or teachers in training through teacher training interventions in sub-Saharan Africa. The interventions included an interactive CD-ROM, a 2-day workshop, and peer facilitated workshops. Both studies demonstrated a significant decrease in HIV stigma in at least one study measure. Findings from this review are inconclusive. There is evidence to suggest that interventions can successfully decrease HIV stigma among teachers, but it is very limited. More research is needed in order to develop, implement, and evaluate stigma reducing interventions in the classroom.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Adolescente , Humanos , Instituições Acadêmicas , Estigma Social , EstudantesRESUMO
BACKGROUND: For adolescents living with HIV (ALWH), school may be the most important but understudied social sphere related to HIV stigma. Teachers are role models in the classroom and within the community, and their attitudes and behavior towards people living with HIV may have critical psychosocial and treatment ramifications. Altering teachers' knowledge, attitudes and beliefs (K/A/B) about HIV could reduce the stigmatizing content within their teaching, classrooms and school, improving the environment for ALWH. METHODS: We developed a one-day teacher training module to enrich teacher K/A/B that included lecture presentations, HIV films and educational animation, structured instructions for teacher role play scenarios, and a question-and-answer session facilitated by a trained ALWH peer educator. We also conducted key informant interviews with education sector subject matter experts (SMEs), including education officers, county commissioners and head teachers to review and provide feedback on the teacher training module. RESULTS: We assembled an adolescent community advisory board and recruited 50 SMEs to review the training module and provide feedback. All SME participants stressed the importance and need for interventions to reduce stigma in the classroom, highlighting their own experiences observing stigmatizing behaviors in the community. The participants perceived the training as culturally relevant and easy to understand and had minor suggestions for improvement, including using image-based resources and brighter colors for ease of reading. All participants thought that the training should be expanded outside of the schools, as all people in a community have a role in the reduction of HIV stigma, and offered suggestions for other settings for implementation. CONCLUSION: Data from interviews with education sector stakeholders demonstrate that our process for developing a culturally appropriate multi-media intervention to reduce HIV stigma in the schools was feasible.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Capacitação de Professores , Adolescente , Infecções por HIV/prevenção & controle , Humanos , Quênia , Instituições Acadêmicas , Estigma SocialRESUMO
Pre-exposure prophylaxis (PrEP) has the potential to prevent new HIV infections, but it is unclear how state policies governing sexual and reproductive health services (SRH) impact access for cisgender women. The objective of this review is to identify barriers to PrEP access for cisgender women in the United States. Using the CDC Atlas Program, 20 states with the highest HIV incidence among cisgender women were included in this analysis. Through a search conducted in May-July 2022 of CDC, PrEPWatch.org, and other State Department and Insurance websites, Medicaid expansion status, pharmacist PrEP prescribing laws, financial support programs, and Traditional Medicaid coverage of PrEP, HIV testing, and emergency contraception were reviewed. Of the included states, nearly half did not expand Medicaid at the state level. Emergency contraception and HIV testing was covered under Traditional Medicaid for almost all included states, but insurance stipulations and eligibility requirements remain. Although PrEP is covered under all Traditional Medicaid plans, six states require pre-authorization. Three states have HIV testing mandates, four allow pharmacists to prescribe PrEP and six have financial support programs to cover the cost of PrEP. Medicaid expansion, pre-authorization requirements for PrEP prescriptions and emergency contraception, and limitations on pharmacist prescribing abilities were identified as barriers to SRH access for cisgender women. Medicaid expansion should be prioritized as an approach to expanding access to HIV prevention services at the state level.
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Infecções por HIV , Acessibilidade aos Serviços de Saúde , Medicaid , Profilaxia Pré-Exposição , Humanos , Estados Unidos , Medicaid/estatística & dados numéricos , Profilaxia Pré-Exposição/estatística & dados numéricos , Profilaxia Pré-Exposição/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Feminino , Infecções por HIV/prevenção & controle , Política de Saúde , Serviços de Saúde Reprodutiva/estatística & dados numéricos , Governo Estadual , Saúde Sexual/estatística & dados numéricosRESUMO
This scoping review provides an up-to-date overview of the evidence on adolescent and youth-friendly health services (AYFHS) in sub-Saharan African countries. We conducted a search of four databases and grey literature sources to identify English language publications from January 1, 2005, to December 14th, 2022. The review synthesized evidence on the models and characteristics of AYFHS, the application of World Health Organization (WHO) standards, and whether AYFHS have improved young people's health outcomes. In total, 77 sources were included in the review, representing 47 AYFHS initiatives spanning 19 countries, and three multi-country reports. Most commonly, AYFHS were delivered in public health facilities and focused on sexual and reproductive health, with limited application of WHO standards. Some evidence suggested that AYFHS increased young people's health service utilization and contraceptives uptake. There is a clear need to strengthen and develop innovative and multi-pronged approaches to delivering and evaluating AYFHS in this region.
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Serviços de Saúde do Adolescente , Humanos , África Subsaariana , Adolescente , Feminino , Serviços de Saúde Reprodutiva , Acessibilidade aos Serviços de Saúde , MasculinoRESUMO
BACKGROUND: Youth living with HIV with perinatal infection spend a lifetime taking antiretroviral treatment (ART) to suppress the virus, and face significant challenges to successfully maintaining ART adherence. Tools to measure adherence include self-report, medication event monitoring system (MEMS) pill bottle caps, pill counts, and plasma or hair drug levels; however, the inter-rater agreement between child and caregiver self-report has not been validated in an African setting. This study aims to assess inter-rater agreement between child and caregiver self-reports, compared to reporting from MEMS pill bottle caps. METHODS: This was a secondary analysis of a cluster-randomized trial to evaluate an intervention for children living with HIV, conducted at the Academic Model Providing Access to Healthcare in western Kenya. We analyzed data from 285 child-caregiver dyads to compare adherence self-reported by children and their caregivers, and subsequently compared all self-reports to adherence reported by MEMS pill bottle caps to determine whether child or caregiver self-reports aligned more closely with adherence measured by MEMS. RESULTS: Children and their caregivers reported similar levels of adherence and numbers of missed doses in the past month, and both reports were similarly associated with adherence reported by MEMS pill bottle caps. Children with a caregiver that was not a biological parent were significantly more likely to report more missed doses than their caregiver. The correlation coefficient for the relationship between the child and caregiver self-reports was 0.71; for the relationship between child report and MEMS was 0.23; and for the relationship between caregiver report and MEMS was 0.20. Both children and caregivers under-reported non-adherence compared to MEMS data. CONCLUSION: Children and caregiver self-reports were generally similar in reporting adherence and were not highly correlated with MEMS reports of adherence, with children and caregivers reporting higher level of adherence than the MEMS data. This may indicate that children and caregiver reports are similarly inaccurate or biased; however, further research with larger sample sizes is required to further understand the differences in these reports.
Comparison of self-reported ART adherence rates among children and adolescents living with HIV in western Kenya The study aims to compare adherence between children and caregivers of Youth Living with HIV (YLWH) with perinatal infection, comparing data from 285 child-caregiver dyads and MEMS pill bottle caps. Results showed similar levels of adherence and missed doses in the past month, with a correlation coefficient of 0.71. However, children and caregivers reported higher levels of adherence than MEMS data. The study highlights the importance of understanding the reliability between self-reports and MEMS data in promoting adherence among YLWH.
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Cuidadores , Infecções por HIV , Adolescente , Humanos , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Quênia/epidemiologia , Adesão à MedicaçãoRESUMO
Objectives: This review seeks to critically analyze studies assessing gender differences in HIV-related knowledge among adolescents and young people in low- and middle-income countries. Methods: Using PRISMA guidelines and searching Pubmed and Scopus online databases, the search strategy combined search keywords with Boolean operators: (HIV OR AIDS) AND (knowledge) AND (gender) AND (adolescents). AC and EG conducted the search and independently reviewed all articles in Covidence software; conflicts were resolved by GC. Articles were included if they evaluated differences in HIV knowledge in at least two groups ages 10-24 and were implemented in a low or middle-income country. Results: The search resulted in 4,901 articles, of which fifteen studies, implemented in 15 countries, met selection criteria. Twelve evaluated differences in HIV knowledge in school settings; three evaluated participants in clinic settings. Adolescent males consistently scored higher in composite knowledge scores, as well as knowledge of HIV transmission, prevention, attitudes and sexual decision-making. Conclusion: We found gender-based discrepancies between knowledge, perception of risk and HIV prevalence among youth globally, with boys consistently scoring higher in HIV knowledge. However, there is significant evidence that social and cultural contexts render girls at high risk of HIV infection, and the gaps in girls' knowledge and boys' roles in HIV risk must be addressed urgently. Future research should consider interventions that facilitate discussion and HIV knowledge building across genders.
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Research engaging children and adolescents living with HIV (CALWH) is critical for youth-friendly services and HIV care, and researchers need to ensure that such engagement is ethical. We conducted a systematic review to identify key ethical considerations for the engagement of CALWH in research. The review focused on primary research articles conducted in African countries that examined ethical issues in CALWH engaged in research. Ten studies met the inclusion criteria; the following seven key domains were extracted: 1) justifications for engaging CALWH in research; 2) community involvement; 3) informed consent/assent; 4) caregiver involvement; 5) perceptions of benefits; 6) perception of the risks of involvement; and 7) confidentiality. These domains can inform the ethical engagement of CALWH in research.
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Participação da Comunidade , Infecções por HIV , Humanos , Adolescente , Criança , Consentimento Livre e Esclarecido , Pesquisadores , Inquéritos e QuestionáriosRESUMO
Introduction: Engaging youth living with HIV (YLWH) in research is critical to improving HIV-related outcomes, but their involvement raises unaddressed bioethical questions. Methods: This study used qualitative inquiry with Kenyan YLWH, caregivers, and subject matter experts (SMEs) to evaluate ethical considerations and strategies for research involving YLWH. Results: Interviews were conducted with 99 participants: 40 YLWH (median age 17.5, 50% female), 20 caregivers (70% female), and 39 SMEs (44% female). All participant groups discussed the need for HIV disclosure status assessment, confidentiality, and engagement of caregivers. Youth participants discussed the importance of clear protocol explanations and developing good rapport. All participant groups perceived youth under 18 to be harder to recruit due to a number of identified barriers. Clinic settings were the most acceptable place for recruitment. Conclusion: Participants provided perspectives on engaging YLWH in research that can be incorporated into protocols and regulatory guidelines.
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Infecções por HIV , HIV , Humanos , Adolescente , Feminino , Masculino , Quênia , Cuidadores , RevelaçãoRESUMO
Drug resistance remains a global challenge in children and adolescents living with HIV (CALWH). Characterizing resistance evolution, specifically using next generation sequencing (NGS) can potentially inform care, but remains understudied, particularly in antiretroviral therapy (ART)-experienced CALWH in resource-limited settings. We conducted reverse-transcriptase NGS and investigated short-and long-term resistance evolution and its predicted impact in a well-characterized cohort of Kenyan CALWH failing 1st-line ART and followed for up to ~8 years. Drug resistance mutation (DRM) evolution types were determined by NGS frequency changes over time, defined as evolving (up-trending and crossing the 20% NGS threshold), reverting (down-trending and crossing the 20% threshold) or other. Exploratory analyses assessed potential impacts of minority resistance variants on evolution. Evolution was detected in 93% of 42 participants, including 91% of 22 with short-term follow-up, 100% of 7 with long-term follow-up without regimen change, and 95% of 19 with long-term follow-up with regimen change. Evolving DRMs were identified in 60% and minority resistance variants evolved in 17%, with exploratory analysis suggesting greater rate of evolution of minority resistance variants under drug selection pressure and higher predicted drug resistance scores in the presence of minority DRMs. Despite high-level pre-existing resistance, NGS-based longitudinal follow-up of this small but unique cohort of Kenyan CALWH demonstrated continued DRM evolution, at times including low-level DRMs detected only by NGS, with predicted impact on care. NGS can inform better understanding of DRM evolution and dynamics and possibly improve care. The clinical significance of these findings should be further evaluated.
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Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Criança , Humanos , Adolescente , HIV-1/genética , Quênia , Sequenciamento de Nucleotídeos em Larga Escala , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Mutação , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , GenótipoRESUMO
Background: The HADITHI study is a cluster-randomized trial of children living with HIV and their caregivers in Kenya that aimed to increase rates of caregiver disclosure of their child's HIV status, encourage earlier status disclosure, and improve pediatric mental health and HIV outcomes. This analysis identified characteristics predicting caregiver non-responsiveness and compared outcomes among children based on disclosure status. Methods: A penalized logistic regression model with lasso regularization identified the most important predictors of disclosure. The two-stage least squares instrumental variable approach was used to assess outcomes accounting for non-compliance to disclosure. Results: Caregiver non-isolation and shorter time on antiretroviral therapy were predictive of HIV status disclosure. There were no statistically significant differences found in CD4 percentage, depression status, or mental and emotional status based on disclosure status up to 24 months-post intervention. Conclusion: These findings have implications for specialists seeking to tailor disclosure interventions to improve caregiver-child dyad responsiveness.
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Cuidadores , Infecções por HIV , Humanos , Criança , Cuidadores/psicologia , Quênia , Revelação da Verdade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Adesão à Medicação , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Introduction: HIV stigma affects medication adherence, psychosocial outcomes, and clinical management for youth living with HIV (YLWH). We explored the impact of HIV stigma on research participation, to inform the ethical engagement of this vulnerable group. Methods: We interviewed 40 YLWH, 20 caregivers, and 39 subject matter experts (SMEs); transcripts were analyzed by HK and EG, with emerging themes confirmed by JA and AC. Results: All categories of participants identified the impacts of stigma on YLWH research participation, suggesting implementing privacy protections, considering recruitment locations carefully, and developing supportive relationships with YLWH. SMEs suggested that YLWH experience uniquely high risks from stigma due to the compounding effects of developmental challenges and transitionary life period. Accidental HIV disclosure and subsequent stigma were identified as a risk of research participation; some viewed the creation of community through research as a benefit. Conclusion: Participants provided insights into stigma-related considerations for research with YLWH, which may guide engagement protocols.
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Infecções por HIV , Humanos , Adolescente , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , HIV , Quênia , Estigma Social , Adesão à MedicaçãoRESUMO
Abstract Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent 'neurogenic' imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.
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Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/metabolismo , Fenótipo , Biomarcadores , Transcriptoma , Inflamação/metabolismoRESUMO
STUDY DESIGN: In a pilot study from an American College of Surgeons (ACS)-verified Level One Trauma Center, we performed a retrospective analysis of patients with cervical spine fractures with or without spinal cord injury (SCI). Long-term mortality was determined from the National Death Index as of December 31, 2013. OBJECTIVE: Examine the influence of age and presence of SCI on time-to-surgery and long-term mortality in patients with cervical spine fractures. SUMMARY OF BACKGROUND DATA: Cervical spine fractures with or without SCI disproportionately impact the elderly, who constitute an increasing percentage of the US population. Early surgical intervention is a safe, modifiable factor that enables early mobilization and may reduce complications. Because of increased comorbidities, surgical treatment of elderly patients with cervical spinal fractures is complex, but prolonged time to surgery is increasingly considered as a factor impacting potential recovery after SCI. MATERIALS AND METHODS: Retrospective chart review using hospital medical charts and mortality data from the National Death Index. RESULTS: Data from patients with cervical spine fractures treated surgically were analyzed, with nearly equal numbers under and over age 65. There was no statistically significant difference between the 2 age groups with respect to time-to-surgery or long-term mortality. In addition, there was no statistically significant difference between the 2 groups of patients, with or without SCI, with respect to time-to-surgery or long-term mortality. CONCLUSIONS: There was no statistically significant differences between patients by age or by SCI status with respect to time-to-surgery or long-term mortality.
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Fraturas Ósseas , Traumatismos da Medula Espinal , Fraturas da Coluna Vertebral , Idoso , Vértebras Cervicais/lesões , Vértebras Cervicais/cirurgia , Humanos , Projetos Piloto , Estudos Retrospectivos , Traumatismos da Medula Espinal/cirurgia , Fraturas da Coluna Vertebral/complicaçõesRESUMO
An estimated 3.4 million youth aged 15-24 years live with human immunodeficiency virus (HIV), a majority of whom reside in sub-Saharan Africa (SSA). Youth living with HIV (YLHIV) generally maintain lower levels of antiretroviral therapy (ART) adherence compared to other age groups, which has negative impacts on long-term clinical outcomes. Given expanding mobile phone and Internet usage among youth in SSA, and a need for strategies to increase ART adherence, this review systematically assessed whether digital interventions could be used to improve YLHIV ART adherence in SSA. PRISMA 2020 guidelines were followed, and PubMed and Scopus databases were searched using terms to reflect the population of interest and different digital intervention strategies to improve ART adherence. Experimental or quasi-experimental studies in SSA evaluating the quantitative effect of digital interventions on YLHIV ART adherence were included. 3849 articles and abstracts, and 122 full texts were screened by two researchers (KG and RM). A third researcher (AC) resolved conflicts. Data were extracted from six eligible articles published between 2017 and 2021. Interventions from included studies lasted 13-96 weeks and took place in Kenya, Nigeria, Uganda, and Zimbabwe. Two of the six studies found significant intervention-related improvements in viral suppression. Of these two studies, one used short message service (SMS) for appointment and daily adherence reminders, and the other combined weekly SMS reminders with phone calls, support groups, home visits, and clinic-based counseling. The four remaining studies, using SMS and Internet-based interventions, did not find any significant adherence-related improvements. This review provides mixed evidence for using digital interventions to improve ART adherence among YLHIV in SSA. Given the relative novelty of using digital interventions in this context, further research is required to evaluate their effectiveness in improving youth ART adherence.
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Introduction. Adolescents (10-19 years) living with HIV (ALWH) face unique challenges in controlling HIV long-term, including stigma and perception of stigma within their communities. Methods. We conducted a qualitative investigation of the sources of perceived HIV-related stigma with ALWH in western Kenya. Forty-six ALWH on ART, aware of their status, and engaged in care were enrolled. Interviews explored perceived stigma by probing the individuals and experiences that adolescents identify as causing or perpetuating their ongoing fears. Results. Participants (54% male, mean age 17.4) reported ongoing fears of stigmatization related to friends and peers not living with HIV. They described previous enacted and first-hand observations of stigma, most often occurring in pre-adolescence, by age mates or peers at school as the most common cause for their ongoing fears. Conclusions. Perceived stigma is prevalent among ALWH and develops from experiences in pre-adolescence. Anti-HIV stigma interventions addressing educators and children in school settings to combat perceived stigma at its source should be investigated.
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HIV-1 drug resistance remains a global challenge, yet access to testing is limited, particularly in resource-limited settings. We examined feasibility and limitations of genotyping using dried filter analytes in treatment-experienced Kenyan youth with HIV. Youth infected with HIV perinatally were enrolled in 2016-2018 at the Academic Model Providing Access to Healthcare in Eldoret, western Kenya. Samples were shipped in real-time at ambient temperature to the US, and those with viral load (VL)>1,000 copies/mL were tested based on convenience. Dried blood spots genotyping was attempted when unsuccessful from Hemaspots. Multiple logistic regression was used to examine predictors of genotyping success. Samples from 49 participants (median age 15 years, 43% female, median CD4 496 cells/µL [18%], median 8 years on therapy, median VL 11,827 copies/mL) were shipped after median 7 days from collection, arrived in 20 shipments after median 5 days, and extracted after median 2 days (1 day for samples processed on arrival; and 42 days for frozen Hemaspots). Overall, 29/49 (59%) samples with VL > 1,000 copies/mL and 25/32 (78%) with VL > 5,000 copies/mL were genotyped by either Hemaspots or DBS. Successful genotyping was associated with higher Hemaspot volume and higher VL. Real-life HIV-1 drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. Findings, particularly relevant where resistance testing is limited for clinical care, raise awareness to implementation practicability of this guidelines-recommended test in care of more individuals and populations. Further optimization of filter analytes is needed to overcome related challenges. IMPORTANCE In this manuscript we use dried filter analytes shipped from Kenya to the US in real time, to demonstrate the real-life feasibility of conducting HIV drug resistance testing in a vulnerable population of young children and adolescents with HIV in a resource limited setting. Such testing, which is recommended in resource-rich settings, is unavailable in most resource limited settings for individual clinical care. We show that real-life HIV drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. These findings raise awareness to the importance of HIV drug resistance for individual care, even in such settings, and emphasize the implementation practicability of this guidelines-recommended test.
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Infecções por HIV , HIV-1 , Adolescente , Criança , Pré-Escolar , Farmacorresistência Viral , Estudos de Viabilidade , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Quênia/epidemiologia , Masculino , Carga ViralRESUMO
BACKGROUND: Long-term impact of drug resistance in perinatally infected children and adolescents living with HIV (CALWH) is poorly understood. We determined drug resistance and examined its long-term impact on failure and mortality in Kenyan CALWH failing first-line non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART). SETTING: Academic Model Providing Access to Healthcare, western Kenya. METHODS: Participants were enrolled in 2010-2013 (timepoint 1) and a subsample re-enrolled after 4-7 years (timepoint 2). Viral load (VL) was performed on timepoint 1 samples, with genotyping of those with detectable VL. Primary endpoints were treatment failure (VL >1000 copies/mL) at and death before timepoint 2. Multinomial regression analysis was used to characterize resistance effect on death, failure, and loss-to-follow-up, adjusting for key variables. RESULTS: The initial cohort (n = 480) was 52% (n = 251) female, median age 8 years, median CD4% 31%, 79% (n = 379) on zidovudine/abacavir + lamivudine + efavirenz/nevirapine for median 2 years. Of these, 31% (n = 149) failed at timepoint 1. Genotypes at timepoint 1, available on n = 128, demonstrated 93% (n = 119) extensive resistance, affecting second line. Of 128, 22 failed at timepoint 2, 17 died, and 32 were lost to follow-up before timepoint 2. Having >5 resistance mutations at timepoint 1 was associated with higher mortality [relative risk ratio (RRR) = 8.7, confidence interval (CI) 2.1 to 36.3] and loss to follow-up (RRR = 3.2, CI 1.1 to 9.2). Switching to second line was associated with lower mortality (RRR <0.05, CI <0.05 to 0.1) and loss to follow-up (RRR = 0.1, CI <0.05 to 0.3). CONCLUSION: Extensive resistance and limited switch to second line in perinatally infected Kenyan CALWH failing first-line ART were associated with long-term failure and mortality. Findings emphasize urgency for interventions to sustain effective, life-long ART in this vulnerable population.