Suchergebnisse

Multinational collaborators in health research face particular ethical challenges when conducting studies involving vulnerable populations such as children. We use an example from our first attempt to implement pediatric assent in the context of a longstanding research and clinical partnership between Kenyan and American medical schools to highlight the ethical and procedural issues related to pediatric assent that must be considered for multinational, pediatric studies. We consider relevant domestic, professional, and international guidelines for assent in pediatric research subjects, and we discuss the particular ethical challenges related to pediatric assent in the Kenyan context. Finally, we propose a way forward for approaching pediatric assent within our collaborative research program in Kenya that may apply to other multinational research partnerships.

IntroductionAs highly active antiretroviral therapy (HAART) transforms human immunodeficiency virus (HIV) into a manageable chronic disease, new challenges are emerging in treating children born with HIV, including a number of risks to their physical and psychological health due to HIV infection and its lifelong treatment.MethodsWe conducted a literature review to evaluate the evidence on the physical and psychological effects of perinatal HIV (PHIV+) infection and its treatment in the era of HAART, including major chronic comorbidities.Results and discussionPerinatally infected children face concerning levels of treatment failure and drug resistance, which may hamper their long‐term treatment and result in more significant comorbidities. Physical complications from PHIV+ infection and treatment potentially affect all major organ systems. Although treatment with antiretroviral (ARV) therapy has reduced incidence of severe neurocognitive diseases like HIV encephalopathy, perinatally infected children may experience less severe neurocognitive complications related to HIV disease and ARV neurotoxicity. Major metabolic complications include dyslipidaemia and insulin resistance, complications that are associated with both HIV infection and several ARV agents and may significantly affect cardiovascular disease risk with age. Bone abnormalities, particularly amongst children treated with tenofovir, are a concern for perinatally infected children who may be at higher risk for bone fractures and osteoporosis. In many studies, rates of anaemia are significantly higher for HIV‐infected children. Renal failure is a significant complication and cause of death amongst perinatally infected children, while new data on sexual and reproductive health suggest that sexually transmitted infections and birth complications may be additional concerns for perinatally infected children in adolescence. Finally, perinatally infected children may face psychological challenges, including higher rates of mental health and behavioural disorders. Existing studies have significant methodological limitations, including small sample sizes, inappropriate control groups and heterogeneous definitions, to name a few.ConclusionsSuccess in treating perinatally HIV‐infected children and better understanding of the physical and psychological implications of lifelong HIV infection require that we address a new set of challenges for children. A better understanding of these challenges will guide care providers, researchers and policymakers towards more effective HIV care management for perinatally infected children and their transition to adulthood.

IntroductionInforming children of their own HIV status is an important aspect of long‐term disease management, yet there is little evidence of how and when this type of disclosure takes place in resource‐limited settings and its impact.MethodsMEDLINE, EMBASE and Cochrane Databases were searched for the terms hiv AND disclos* AND (child* OR adolesc*). We reviewed 934 article citations and the references of relevant articles to find articles describing disclosure to children and adolescents in resource‐limited settings. Data were extracted regarding prevalence of disclosure, factors influencing disclosure, process of disclosure and impact of disclosure on children and caregivers.ResultsThirty‐two articles met the inclusion criteria, with 16 reporting prevalence of disclosure. Of these 16 studies, proportions of disclosed children ranged from 0 to 69.2%. Important factors influencing disclosure included the child's age and perceived ability to understand the meaning of HIV infection and factors related to caregivers, such as education level, openness about their own HIV status and beliefs about children's capacities. Common barriers to disclosure were fear that the child would disclose HIV status to others, fear of stigma and concerns for children's emotional or physical health. Disclosure was mostly led by caregivers and conceptualized as a one‐time event, while others described it as a gradual process. Few studies measured the impact of disclosure on children. Findings suggested adherence to antiretroviral therapy (ART) improved post‐disclosure but the emotional and psychological effects of disclosure were variable.ConclusionsMost studies show that a minority of HIV‐infected children in resource‐limited settings know his/her HIV status. While caregivers identify many factors that influence disclosure, studies suggest both positive and negative effects for children. More research is needed to implement age‐ and culture‐appropriate disclosure in resource‐limited settings.

Background: Kenya experienced a political and humanitarian crisis following presidential elections on 27 December 2007. Over 1,200 people were killed and 300,000 displaced, with disproportionate violence in western Kenya. We sought to describe the immediate impact of this conflict on return to clinic and medication adherence for HIV-infected children cared for within the USAID-Academic Model Providing Access to Healthcare (AMPATH) in western Kenya. Methods: We conducted a mixed methods analysis that included a retrospective cohort analysis, as well as key informant interviews with pediatric healthcare providers. Eligible patients were HIV-infected children, less than 14 years of age, seen in the AMPATH HIV clinic system between 26 October 2007 and 25 December 2007. We extracted demographic and clinical data, generating descriptive statistics for pre- and post-conflict antiretroviral therapy (ART) adherence and post-election return to clinic for this cohort. ART adherence was derived from caregiver-report of taking all ART doses in past 7 days. We used multivariable logistic regression to assess factors associated with not returning to clinic. Interview dialogue from was analyzed using constant comparison, progressive coding and triangulation. Results: Between 26 October 2007 and 25 December 2007, 2,585 HIV-infected children (including 1,642 on ART) were seen. During 26 December 2007 to 15 April 2008, 93% (N = 2,398) returned to care. At their first visit after the election, 95% of children on ART (N = 1,408) reported perfect ART adherence, a significant drop from 98% pre-election (p < 0.001). Children on ART were significantly more likely to return to clinic than those not on ART. Members of tribes targeted by violence and members of minority tribes were less likely to return. In qualitative analysis of 9 key informant interviews, prominent barriers to return to clinic and adherence included concerns for personal safety, shortages of resources, hanging priorities, and hopelessness. Conclusion: During a period of humanitarian crisis, the vulnerable, HIV-infected pediatric population had disruptions in clinical care and in medication adherence, putting children at risk for viral resistance and increased morbidity. However, unique program strengths may have minimized these disruptions.

IntroductionThe objective of this analysis was to identify points of disruption within the prevention of mother‐to‐child transmission (PMTCT) continuum from combination antiretroviral therapy (CART) initiation until delivery.MethodsTo address this objective, the electronic medical records of all antiretroviral‐naïve adult pregnant women who were initiating CART for PMTCT between January 2006 and February 2009 within the Academic Model Providing Access To Healthcare (AMPATH), western Kenya, were reviewed. Outcomes of interest were clinician‐initiated change or stop in regimen, disengagement from programme (any, early, late) and self‐reported medication adherence. Disengagement was categorized as early disengagement (any interval of greater than 30 days between visits but returning to care prior to delivery) or late disengagement (no visit within 30 days prior to the date of delivery). The association between covariates and the outcomes of interest were assessed using bivariate (Kruskal‐Wallis test for continuous variables and the Chi‐square test for categorical variables) and multivariate logistic regression analysis.ResultsA total of 4284 antiretroviral‐naïve pregnant women initiated CART between January 2006 and February 2009. The majority of women (89%) reported taking all of their medication at every visit. There were 18 (0.4%) deaths reported. Clinicians discontinued CART in 10 patients (0.7%) while 1367 (31.9%) women disengaged from care. Of those disengaging, 404 (29.6%) disengaged early and 963 (70.4%) late. In the multivariate model, the odds of disengagement decreased with increasing age (odds ratio [OR] 0.982; confidence interval [CI] 0.966–0.998) and increasing gestational age at CART initiation (OR 0.925; CI 0.909–0.941). Women receiving care at a district hospital (OR 0.794; CI 0.644–0.980) or tuberculosis medication (OR 0.457; CI 0.202–0.935) were less likely to disengage. The odds of disengagement were higher in married women (OR 1.277; CI 1.034–1.584). The odds of early disengagement decreased with increasing age at CART initiation (OR 0.902; CI 0.881–0.924). The odds of late disengagement decreased with increasing age at CART initiation (OR 0.936; CI 0.917–0.956). While they increased with higher CD4 counts at CART‐initiation (OR 1.001; CI 1.000–1001) and in married women (OR 1.297; CI 1.000–1.695)ConclusionsIn a PMTCT programme embedded in an antiretroviral treatment programme with an active outreach department, the majority (67.4%) of women remained engaged and received uninterrupted prenatal CART.

Orphans are a subpopulation with a unique set of additional vulnerabilities. Increasing focus on children's rights, pediatric global health, and pediatric research makes it imperative to recognize and address unique vulnerabilities of orphaned children. This paper describes the unique vulnerabilities of the orphaned pediatric population and offers a structured set of factors that require consideration when including orphans in biomedical research. Pediatric orphans are particularly vulnerable due to decreased economic resources, psychosocial instability, increased risk of abuse, and delayed/decreased access to healthcare. These vulnerabilities are significant. By carefully considering each issue in a population in a culturally specific and study-specific manner, researchers can make valuable contributions to the overall health and well-being of this uniquely vulnerable population.

AbstractBackground: Traditional medication adherence measures do not account for the pharmacokinetic (PK) properties of the drugs, potentially misrepresenting true therapeutic exposure.Methods: In a population of HIV‐infected Kenyan children on antiretroviral therapy including nevirapine (NVP), we used a one‐compartment model with previously established PK parameters and Medication Event Monitoring Systems (MEMS®)‐recorded dosing times to estimate the mean plasma concentration of NVP (Cp) in individual patients during 1 month of follow‐up. Intended NVP concentration (Cp') was calculated under a perfectly followed dosing regimen and frequency. The ratio between the two (R = Cp/Cp') characterized the patient's NVP exposure as compared to intended level. Smaller R values indicated poorer adherence. We validated R by evaluating its association with MEMS®‐defined adherence, CD4%, and spot‐check NVP plasma concentrations assessed at 1 month.Results: In data from 152 children (82 female), children were mean age 7.7 years (range 1.5–14.9) and on NVP an average of 2.2 years. Mean MEMS® adherence was 79%. The mean value of R was 1.11 (SD 0.37). R was positively associated with MEMS® adherence (p < 0.0001), and lower‐than‐median R values were significantly associated with lower NVP drug concentrations (p = 0.0018) and lower CD4% (p = 0.0178), confirming a smaller R value showed poorer adherence.Conclusion: The proposed adherence measures, R, captured patient drug‐taking behaviours and PK properties.

IntroductionHIV‐related stigma impacts the quality of life and care management of HIV‐infected and HIV‐affected individuals, but how we measure stigma and its impact on children and adolescents has less often been described.MethodsWe conducted a systematic review of studies that measured HIV‐related stigma with a quantitative tool in paediatric HIV‐infected and HIV‐affected populations.Results and discussionVarying measures have been used to assess stigma in paediatric populations, with most studies utilizing the full or variant form of the HIV Stigma Scale that has been validated in adult populations and utilized with paediatric populations in Africa, Asia and the United States. Other common measures included the Perceived Public Stigma Against Children Affected by HIV, primarily utilized and validated in China. Few studies implored item validation techniques with the population of interest, although scales were used in a different cultural context from the origin of the scale.ConclusionsMany stigma measures have been used to assess HIV stigma in paediatric populations, globally, but few have implored methods for cultural adaptation and content validity.

Involving vulnerable pediatric populations in international research requires culturally appropriate ethical protections. We sought to use mabaraza, traditional East African community assemblies, to understand how a community in western Kenya viewed participation of children in health research and informed consent and assent processes. Results from 108 participants revealed generally positive attitudes towards involving vulnerable children in research, largely because they assumed children would directly benefit. Consent from parents or guardians was understood as necessary for participation while gaining child assent was not. They felt other caregivers, community leaders, and even community assemblies could participate in the consent process. Community members believed research involving orphans and street children could benefit these vulnerable populations, but would require special processes for consent.

IntroductionHigh levels of adherence to antiretroviral therapy (ART) are central to HIV management. The objective of this study was to compare multiple measures of adherence and investigate factors associated with adherence among HIV‐infected children in western Kenya.MethodsWe evaluated ART adherence prospectively for six months among HIV‐infected children aged ≤14 years attending a large outpatient HIV clinic in Kenya. Adherence was reported using caregiver report, plasma drug concentrations and Medication Event Monitoring Systems (MEMS®). Kappa statistics were used to compare adherence estimates with MEMS®. Logistic regression analyses were performed to assess the association between child, caregiver and household characteristics with dichotomized adherence (MEMS® adherence ≥90% vs. <90%) and MEMS® treatment interruptions of ≥48 hours. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsAmong 191 children, mean age at baseline was 8.2 years and 55% were female. Median adherence by MEMS® was 96.3% and improved over the course of follow‐up (p<0.01), although 49.5% of children had at least one MEMS® treatment interruption of ≥48 hours. Adherence estimates were highest by caregiver report, and there was poor agreement between MEMS® and other adherence measures (Kappa statistics 0.04–0.37). In multivariable logistic regression, only caregiver‐reported missed doses in the past 30 days (OR 1.25, 95% CI 1.14–1.39), late doses in the past seven days (OR 1.14, 95% CI 1.05–1.22) and caregiver‐reported problems with getting the child to take ART (OR 1.10, 95% CI 1.01–1.20) were significantly associated with dichotomized MEMS® adherence. The caregivers reporting that ART made the child sick (OR 1.12, 95% CI 1.01–1.25) and reporting difficulties in the community that made giving ART more difficult (e.g. stigma) (OR 1.14, 95% CI 1.02–1.27) were significantly associated with MEMS® treatment interruptions in multivariable logistic regression.ConclusionsNon‐adherence in the form of missed and late doses, treatment interruptions of more than 48 hours and sub‐therapeutic drug levels were common in this cohort. Adherence varied significantly by adherence measure, suggesting that additional validation of adherence measures is needed. Few factors were consistently associated with non‐adherence or treatment interruptions.

AbstractIntroductionThere are few data on adherence and low‐cost measurement tools for children living with HIV. We collected prospective data on adherence to antiretroviral therapy (ART) among a multinational cohort of children to evaluate an adherence questionnaire.MethodsWe enrolled 319 children ages 0 to 16 years on ART in Kenya (n = 110), South Africa (n = 109) or Thailand (n = 100). Children were followed up for six months of adherence monitoring between March 2015 and August 2016 using Medication Event Monitoring Systems (MEMS®) with at least one viral load measure. At month 3 and 6, children or their caregivers were administered a 10‐item adherence questionnaire. Repeated measures analyses were used to compare responses on questionnaire items to external adherence criteria: MEMS® dichotomized adherence (≥90% of doses taken vs. <90%), 48‐hour MEMS® treatment interruptions and viral suppression (<1000 copies/mL). Items associated with outcomes (p < 0.10) were coefficient‐weighted to calculate a total adherence score, which was tested in multivariate regression against MEMS® and viral suppression outcomes. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated.ResultsMean child age was 11 years and 54% were female. Children from Thailand (median age 14 years) were significantly older compared to Kenya (10 years) and South Africa (10 years). Prevalence of viral suppression was 97% in Thailand, 81% in South Africa and 69% in Kenya, while the prevalence of MEMS® adherence ≥90% was 57% in Thailand, 58% in South Africa and 40% in Kenya. Across sites, child‐reported adherence using the questionnaire was significantly associated with dichotomized MEMS® adherence (OR 1.8, 95% CI 1.4 to 2.4), 48‐hour treatment interruptions (OR 0.41, 95% CI 0.3 to 0.6), and viral suppression (OR 3.4, 95% CI 1.7 to 6.7). We did find, however, that different cut‐points for the adherence score may be context‐specific. For example, MEMS® non‐adherent children in Kenya had a lower adherence score (0.98) compared to South Africa (1.77) or Thailand (1.58).ConclusionsWe found suboptimal adherence to ART was common by multiple measures in this multi‐country cohort of children. The short‐form questionnaire demonstrated reasonable validity to screen for non‐adherence in these diverse settings.

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.