The Vulnerabilities of Orphaned Children Participating in Research: A Critical Review and Factors for Consideration for Participation in Biomedical and Behavioral Research

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

Prevalence of sexually transmitted infections including HIV in street-connected adolescents in western Kenya

PURPOSE: The objectives of this study were to characterise the sexual health of street-connected adolescents in Eldoret, Kenya, analyse gender disparity of risks, estimate the prevalence of sexually transmitted infections (STIs), and identify factors associated with STIs. METHODS: A cross-sectional study of street-connected adolescents ages 12-21 years was conducted in Eldoret, Kenya. Participants were interviewed and screened for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, herpes simplex virus-2, syphilis and HIV. Descriptive statistics and logistic regression were used to identify factors associated with having any STI. RESULTS: Of the 200 participants, 81 (41%) were female. 70.4% of females and 60.5% of males reported sexual activity. Of those that participated in at least one STI test, 28% (55/194) had ≥1 positive test, including 56% of females; 14% (28/194) had >1 positive test. Twelve females and zero males (6% overall, 14.8% of females) were HIV positive. Among females, those with HIV infection more frequently reported transactional sex (66.7% vs. 26.1%, p=0.01), drug use (91.7% vs. 56.5%, p=0.02), and reported a prior STI (50.0% vs. 14.7%, p<0.01). Having an adult caregiver was less likely among those with HIV infection (33.3% vs. 71.0%, p=0.04). Transactional sex (AOR 3.02, 95% CI (1.05 to 8.73)), a previous STI (AOR 3.46 95% CI (1.05 to 11.46)) and ≥2 sexual partners (AOR 5.62 95% (1.67 to 18.87)) were associated with having any STI. CONCLUSIONS: Street-connected adolescents in Eldoret, Kenya are engaged in high-risk sexual behaviours and females in particular have a substantial burden of STIs and HIV. There is a need for STI interventions targeted to street-connected youth

Acceptance of HIV Testing for Children Ages 18 Months to 13 Years Identified Through Voluntary, Home-Based HIV Counseling and Testing in Western Kenya

Background Home-based, voluntary counseling and testing (HCT) presents a novel approach to early diagnosis. We sought to describe uptake of pediatric HIV testing, associated factors, and HIV prevalence among children offered HCT in Kenya. Methods The USAID-AMPATH Partnership conducted HCT in western Kenya in 2008. Children 18 months to 13 years were offered HCT if their mother was known to be dead, her living status was unknown, mother was HIV-infected or of unknown HIV status. This retrospective analysis describes the cohort of children encountered and tested. Results HCT was offered to 2,289 children and accepted for 1,294 (57%). Children were more likely to be tested if more information was available about a suspected or confirmed maternal HIV-infection (for HIV-infected, living mothers OR=3.20, 95% CI: 1.64–6.23), if parents were not in household (OR=1.50, 95% CI: 1.40–1.63), if they were grandchildren of head of household (OR=4.02, 95% CI: 3.06–5.28), or if their father was not in household (OR=1.41, 95% CI: 1.24–1.56). Of the eligible children tested, 60 (4.6%) were HIV-infected. Conclusions HCT provides an opportunity to identify HIV among high-risk children; however, acceptance of HCT for children was limited. Further investigation is needed to identify and overcome barriers to testing uptake

Antiretroviral Therapy outcomes among adolescents and youth in rural Zimbabwe

Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults

Decreasing incidence of pregnancy among HIV-positive adolescents in a large HIV treatment program in western Kenya between 2005 and 2017: a retrospective cohort study

Background: The objective of this study was to estimate the prevalence, incidence and risk factors for pregnancy among HIV-positive adolescents in a large HIV treatment program in western Kenya. Methods: The Academic Model Providing Access to Healthcare (AMPATH) program is a partnership between Moi University, Moi Teaching and Referral Hospital and a consortium of 11 North American academic institutions. AMPATH currently provides care to 85,000 HIV-positive individuals in western Kenya. Included in this analysis were adolescents aged 10-19 enrolled in AMPATH between January 2005 and February 2017. Socio-demographic, behavioural, and clinical data at baseline and time-updated antiretroviral treatment (ART) data were extracted from the electronic medical records and summarized using descriptive statistics. Follow up time was defined as time of inclusion in the cohort until the date of first pregnancy or age 20, loss to follow up, death, or administrative censoring. Adolescent pregnancy rates and associated risk factors were determined. Results: There were 8565 adolescents eligible for analysis. Median age at enrolment in HIV care was 14.0 years. Only 17.7% had electricity at home and 14.4% had piped water, both indicators of a high level of poverty. 12.9% (1104) were pregnant at study inclusion. Of those not pregnant at enrolment, 5.6% (448) became pregnant at least once during follow-up. Another 1.0% (78) were pregnant at inclusion and became pregnant again during follow-up. The overall pregnancy incidence rate was 21.9 per 1000 woman years or 55.8 pregnancies per 1000 women. Between 2005 and 2017, pregnancy rates have decreased. Adolescents who became pregnant in follow-up were more likely to be older, to be married or living with a partner and to have at least one child already and less likely to be using family planning. Conclusions: A considerable number of these HIV-positive adolescents presented at enrolment into HIV care as pregnant and many became pregnant as adolescents during follow-up. Pregnancy rates remain high but have decreased from 2005 to 2017. Adolescent-focused sexual and reproductive health and ante/postnatal care programs may have the potential to improve maternal and neonatal outcomes as well as further decrease pregnancy rates in this high-risk group

Financing HIV Programming: How Much Should Low- And Middle-Income Countries and their Donors Pay?

Global HIV control funding falls short of need. To maximize health outcomes, it is critical that national governments sustain reasonable commitments, and that international donor assistance be distributed according to country needs and funding gaps. We develop a country classification framework in terms of actual versus expected national domestic funding, considering resource needs and donor financing. With UNAIDS and World Bank data, we examine domestic and donor HIV program funding in relation to need in 84 low- and middle-income countries. We estimate expected domestic contributions per person living with HIV (PLWH) as a function of per capita income, relative size of the health sector, and per capita foreign debt service. Countries are categorized according to levels of actual versus expected domestic contributions, and resource gap. Compared to national resource needs (UNAIDS Investment Framework), we identify imbalances among countries in actual versus expected domestic and donor contributions: 17 countries, with relatively high HIV prevalence and GNI per capita, have domestic funding below expected (median per PLWH $143 and$376, respectively), yet total available funding including from donors would exceed the need ($368 and$305, respectively) if domestic contribution equaled expected. Conversely, 27 countries have actual domestic funding above the expected (medians $294 and$149) but total (domestic+donor) funding does not meet estimated need ($685 and$1,173). Across the 84 countries, in 2009, estimated resource need totaled $10.3 billion, actual domestic contributions$5.1 billion and actual donor contributions $3.7 billion. If domestic contributions would increase to the expected level in countries where the actual was below expected, total domestic contributions would increase to$7.4 billion, turning a funding gap of $1.5 billion into a surplus of$0.8 billion. Even with imperfect funding and resource-need data, the proposed country classification could help improve coherence and efficiency in domestic and international allocations

Continuous increase of cardiovascular diseases, diabetes, and non-HIV related cancers as causes of death in HIV-infected individuals in Brazil: An analysis of nationwide data

Introduction: After antiretroviral therapy (ART) became available, there was a decline in the number of deaths in persons infected with HIV. Thereafter, there was a decrease in the proportion of deaths attributed to opportunistic infections and an increase in the proportion of deaths attributed to chronic comorbidities. Herein we extend previous observations from a nationwide survey on temporal trends in causes of death in HIV-infected patients in Brazil. Methods: We describe temporal trends in causes of death among adults who had HIV/AIDS listed in the death certificate to those who did not. All death certificates issued in Brazil from 1999 to 2011 and listed in the national mortality database were included. Generalized linear mixed-effects logistic models were used to study temporal trends in proportions. Results: In the HIV-infected population, there was an annual adjusted average increase of 6.0%, 12.0%, 4.0% and 4.1% for cancer, external causes, cardiovascular diseases (CVD) and diabetes mellitus (DM), respectively, compared to 3.0%, 4.0%, 1.0% and 3.9%, in the non-HIV group. For tuberculosis (TB), there was an adjusted average increase of 0.3%/year and a decrease of 3.0%/year in the HIV and the non-HIV groups, respectively. Compared to 1999, the odds ratio (OR) for cancer, external causes, CVD, DM, or TB in the HIV group were, respectively, 2.31, 4.17, 1.76, 2.27 and 1.02, while for the non-HIV group, the corresponding OR were 1.31, 1.63, 1.14, 1.62 and 0.67. Interactions between year as a continuous or categorical variable and HIV were significant (p <0.001) for all conditions, except for DM when year was considered as a continuous variable (p = 0.76). Conclusions: Non HIV-related co-morbidities continue to increase more rapidly as causes of death among HIV-infected individuals than in those without HIV infection, highlighting the need for targeting prevention measures and surveillance for chronic diseases among those patients. © 2014 Paula et al

Sampling-Based Approaches to Improve Estimation of Mortality among Patient Dropouts: Experience from a Large PEPFAR-Funded Program in Western Kenya

Monitoring and evaluation (M&E) of HIV care and treatment programs is impacted by losses to follow-up (LTFU) in the patient population. The severity of this effect is undeniable but its extent unknown. Tracing all lost patients addresses this but census methods are not feasible in programs involving rapid scale-up of HIV treatment in the developing world. Sampling-based approaches and statistical adjustment are the only scaleable methods permitting accurate estimation of M&E indices.In a large antiretroviral therapy (ART) program in western Kenya, we assessed the impact of LTFU on estimating patient mortality among 8,977 adult clients of whom, 3,624 were LTFU. Overall, dropouts were more likely male (36.8% versus 33.7%; p = 0.003), and younger than non-dropouts (35.3 versus 35.7 years old; p = 0.020), with lower median CD4 count at enrollment (160 versus 189 cells/ml; p<0.001) and WHO stage 3-4 disease (47.5% versus 41.1%; p<0.001). Urban clinic clients were 75.0% of non-dropouts but 70.3% of dropouts (p<0.001). Of the 3,624 dropouts, 1,143 were sought and 621 had their vital status ascertained. Statistical techniques were used to adjust mortality estimates based on information obtained from located LTFU patients. Observed mortality estimates one year after enrollment were 1.7% (95% CI 1.3%-2.0%), revised to 2.8% (2.3%-3.1%) when deaths discovered through outreach were added and adjusted to 9.2% (7.8%-10.6%) and 9.9% (8.4%-11.5%) through statistical modeling depending on the method used. The estimates 12 months after ART initiation were 1.7% (1.3%-2.2%), 3.4% (2.9%-4.0%), 10.5% (8.7%-12.3%) and 10.7% (8.9%-12.6%) respectively. CONCLUSIONS/SIGNIFICANCE ABSTRACT: Assessment of the impact of LTFU is critical in program M&E as estimated mortality based on passive monitoring may underestimate true mortality by up to 80%. This bias can be ameliorated by tracing a sample of dropouts and statistically adjust the mortality estimates to properly evaluate and guide large HIV care and treatment programs

Impact of the Kenya post-election crisis on clinic attendance and medication adherence for HIV-infected children in western Kenya

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p