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Item Association of Care Environment With HIV Incidence and Death Among Orphaned, Separated, and Street-Connected Children and Adolescents in Western Kenya(American Medical Association, 2021-09-01) Braitstein, Paula; DeLong, Allison; Ayuku, David; Ott, Mary; Atwoli, Lukoye; Galárraga, Omar; Sang, Edwin; Hogan, Joseph; Pediatrics, School of MedicineImportance: In 2015, there were nearly 140 million orphaned children globally, particularly in low- and middle-income regions, and millions more for whom the street is central to their everyday lives. A total of 16.6 million children were orphaned because of deaths associated with HIV/AIDS, of whom 90% live in sub-Saharan Africa. Although most orphaned and separated children and adolescents in this region are cared for by extended family, the large number of children requiring care has produced a proliferation of institutional care. Few studies have investigated the association between care environment and physical health among orphaned and separated youths in sub-Saharan Africa. Objective: To examine the association of care environment with incident HIV and death among orphaned and separated children and adolescents who were living in charitable children's institutions, family-based settings, and street settings in western Kenya over almost 10 years. Design, setting, and participants: The Orphaned and Separated Children's Assessments Related to Their Health and Well-Being (OSCAR) project was an observational prospective cohort study conducted in Uasin Gishu County, Kenya. The cohort comprised 2551 orphaned, separated, and street-connected children from communities within 8 administrative locations, which included 300 randomly selected households (family-based settings) caring for children who were orphaned from all causes, 19 charitable children's institutions (institutional settings), and a convenience sample of 100 children who were practicing self-care on the streets (street settings). Participants were enrolled from May 31, 2010, to April 24, 2013, and were followed up until November 30, 2019. Exposures: Care environment (family-based, institutional, or street setting). Main outcomes and measures: Survival regression models were used to investigate the association between care environment and incident HIV, death, and time to incident HIV or death. Results: Among 2551 participants, 1230 youths were living in family-based settings, 1230 were living in institutional settings, and 91 were living in street settings. Overall, 1321 participants (51.8%) were male, with a mean (SD) age at baseline of 10.4 (4.8) years. Most participants who were living in institutional (1047 of 1230 youths [85.1%]) or street (71 of 91 youths [78.0%]) settings were double orphaned (ie, both parents had died). A total of 59 participants acquired HIV infection or died during the study period. After adjusting for sex, age, and baseline HIV status, living in a charitable children's institution was not associated with death (adjusted hazard ratio [AHR], 0.26; 95% CI, 0.07-1.02) or incident HIV (AHR, 1.49; 95% CI, 0.46-4.83). Compared with living in a family-based setting, living in a street setting was associated with death (AHR, 5.46; 95% CI, 2.30-12.94), incident HIV (AHR, 17.31; 95% CI, 5.85-51.25), and time to incident HIV or death (AHR, 7.82; 95% CI, 3.48-17.55). Conclusions and relevance: In this study, after adjusting for potential confounders, no association was found between care environment and HIV incidence or death among youths living in institutional vs family-based settings. However, living in a street setting vs a family-based setting was associated with both HIV incidence and death. This study's findings suggest that strengthening of child protection systems and greater investment in evidence-based family support systems that improve child and adolescent health and prevent youth migration to the street are needed for safe and beneficial deinstitutionalization to be implemented at scale.Item A Challenging Knowledge Gap: Estimating Modes of HIV Acquisition Among Adolescents Entering HIV Care During Adolescence(Sage, 2022-05-31) Humphrey, John; Triedman, Miranda; Nyandiko, Winstone; Sang, Edwin; Kemboi, Emmanuel; Alera, Marsha; Novitsky, Vlad; Manne, Akarsh; Jepkemboi, Eslyne; Orido, Millicent; Apondi, Edith; Vreeman, Rachel; Wools-Kaloustian, Kara; Kantor, Rami; Medicine, School of MedicineCharacterizing HIV acquisition modes among adolescents with HIV (AHIV) enrolling in care during adolescence is a challenging gap that impacts differential interventions. We explored whether primary data collection with targeted questionnaires may address this gap and improve understanding of risk factors and perceptions about adolescents' HIV acquisition, in Kenyan AHIV entering care at ≥10 years, and their mothers with HIV (MHIV). Clinical data were derived through chart review. Among 1073 AHIV in care, only 26 (2%) met eligibility criteria of being ≥10 years at care enrollment, disclosed to, and with living MHIV. Among 18/26 AHIV-MHIV dyads enrolled (median age of AHIV 14 years), none had documented HIV acquisition modes. Data suggested perinatal infection in 17/18 AHIV, with 1 reported non-perinatal acquisition risk factor, and some discordance between adolescent-mother perceptions of HIV acquisition. In this difficult-to-enroll, vulnerable population of AHIV-MHIV dyads, primary data collection can enhance understanding of AHIV acquisition modes.Item Feasibility of Rapid Case Ascertainment for Cancer in East Africa: An Investigation of Community-Representative Kaposi Sarcoma in the Era of Antiretroviral Therapy(Elsevier, 2021) Semeere, Aggrey; Byakwaga, Helen; Laker-Oketta, Miriam; Freeman, Esther; Busakhala, Naftali; Wenger, Megan; Kasozi, Charles; Ssemakadde, Matthew; Bwana, Mwebesa; Kanyesigye, Michael; Kadama-Makanga, Philippa; Rotich, Elyne; Kisuya, Job; Sang, Edwin; Maurer, Toby; Wools-Kaloustian, Kara; Kambugu, Andrew; Martin, Jeffrey; Medicine, School of MedicineBackground: Rapid case ascertainment (RCA) refers to the expeditious and detailed examination of patients with a potentially rapidly fatal disease shortly after diagnosis. RCA is frequently performed in resource-rich settings to facilitate cancer research. Despite its utility, RCA is rarely implemented in resource-limited settings and has not been performed for malignancies. One cancer and context that would benefit from RCA in a resource-limited setting is HIV-related Kaposi sarcoma (KS) in sub-Saharan Africa. Methods: To determine the feasibility of RCA for KS, we searched for all potential newly diagnosed KS among HIV-infected adults attending three community-based facilities in Uganda and Kenya. Searching involved querying of electronic medical records, pathology record review, and notification by clinicians. Upon identification, a team verified eligibility and attempted to locate patients to perform RCA, which included epidemiologic, clinical and laboratory measurements. Results: We identified 593 patients with suspected new KS. Of the 593, 171 were ineligible, mainly because biopsy failed to confirm KS (65%) or KS was not new (30%). Among the 422 remaining, RCA was performed within 1 month for 56% of patients and within 3 months for 65% (95% confidence interval: 59 to 70%). Reasons for not performing RCA included intervening death (47%), inability to contact (44%), refusal/unsuitable to consent (8.3%), and patient re-location (0.7%). Conclusions: We found that RCA - an important tool for cancer research in resource-rich settings - is feasible for the investigation of community-representative KS in East Africa. Feasibility of RCA for KS suggests feasibility for other cancers in Africa.Item Growth of young HIV-infected and HIV-exposed children in western Kenya: A retrospective chart review(Public Library of Science, 2019-12-04) McHenry, Megan S.; Apondi, Edith; Ayaya, Samuel O.; Yang, Ziyi; Li, Wenfang; Tu, Wanzhu; Bi, Guanying; Sang, Edwin; Vreeman, Rachel C.; Pediatrics, School of MedicineIntroduction The objective of this study was to determine the growth patterns, rates of malnutrition, and factors associated with malnutrition in children born to HIV-infected mothers in western Kenya using data from an electronic medical record system. Methods This study was a retrospective chart review of HIV-infected (HIV+) and–exposed (HEU) children (<5 years) using data collected prospectively in the course of routine clinical care and stored in the electronic medical record system in western Kenya between January 2011 and August 2016. Demographics and anthropometrics were described, with Chi-square testing to compare proportions. Multiple variable logistic regression analysis was used to identify correlates of children being stunted, underweight, and wasted. We also examined growth curves, using a resampling method to compare the areas under the fitted growth curves to compare males/females and HIV+/HEU. Results Data from 15,428 children were analyzed. The children were 51.6% (n = 7,955) female, 5.2% (n = 809) orphans, 83.3% (n = 12,851) were HEU, and 16.7% (n = 2,577) were HIV+. For HIV+ children assessed at 24 months, 50.9% (n = 217) were stunted, 26.5% (n = 145) were underweight, and 13.6% (n = 58) were wasted, while 45.0% (n = 577) of HEU children were stunted, 14.8% (n = 255) were underweight, and 5.1% (n = 65) were wasted. When comparing mean z-scores, HIV+ children tended to have larger and earlier dips in z-scores compared to HIV-exposed children, with significant differences found between the two groups (p<0.001). Factors associated with an increased risk of malnutrition included being male, HIV+, and attending an urban clinic. Maternal antiretroviral treatment during pregnancy and mixed feeding at 3 months of age decreased the risk of malnutrition. Conclusions HIV+ and HEU children differ in their anthropometrics, with HIV+ children having overall lower z-scores. Continued efforts to develop and implement sustainable and effective interventions for malnutrition are needed for children born to HIV+ mothers.Item Impact of the Kenya post-election crisis on clinic attendance and medication adherence for HIV-infected children in western Kenya(2009-04) Vreeman, Rachel C.; Nyandiko, Winstone M.; Sang, Edwin; Musick, Beverly S.; Braitstein, Paula; Wiehe, Sarah E.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.Item Outcomes After Loss to Follow-Up for Pregnant and Postpartum Women Living With HIV and Their Children in Kenya: A Prospective Cohort Study(Wolters Kluwer, 2024) Humphrey, John; Kipchumba, Bett; Alera, Marsha; Sang, Edwin; Musick, Beverly; Muli, Lindah; Kipsang, Justin; Songok, Julia; Yiannoutsos, Constantin; Wools-Kaloustian, Kara; Medicine, School of MedicineBackground: Many prevention of vertical transmission (PVT) studies assess outcomes within 12 months postpartum and exclude those lost to follow-up (LTFU), potentially biasing outcomes toward those retained in care. Setting: Five public facilities in western Kenya. Methods: We recruited women living with HIV (WLH) ≥18 years enrolled in antenatal clinic (ANC). WLH retained in care (RW) were recruited during pregnancy and followed with their children through 6 months postpartum; WLH LTFU (LW, last visit >90 days) after ANC enrollment and ≤6 months postpartum were recruited through community tracing. Recontact at 3 years was attempted for all participants. Primary outcomes were retention and child HIV-free survival. Generalized linear regression was used to estimated risk ratios (RRs) for associations with becoming LTFU by 6 months postpartum, adjusting for age, education, facility, travel time to facility, gravidity, income, and new vs. known HIV positive at ANC enrollment. Results: Three hundred thirty-three WLH (222 RW, 111 LW) were recruited from 2018 to 2019. More LW versus RW were newly diagnosed with HIV at ANC enrollment (49.6% vs. 23.9%) and not virally suppressed at study enrollment (40.9% vs. 7.7%). 6-month HIV-free survival was lower for children of LW (87.9%) versus RW (98.7%). At 3 years, 230 WLH were retained in care (including 51 previously LTFU before 6 months), 30 transferred, 70 LTFU, and 3 deceased. 3-year child HIV-free survival was 81.9% (92.0% for children of RW, 58.6% for LW), 3.7% were living with HIV, 3.7% deceased, and 10.8% had unknown HIV/vital status. Being newly diagnosed with HIV at ANC enrollment was the only factor associated with becoming LTFU (aRR 1.21, 95% CI: 1.11 to 1.31). Conclusions: Outcomes among those LTFU were worse than those retained in care, underscoring the importance of retention in PVT services. Some, but not all, LW re-engaged in care by 3 years, suggesting the need for PVT services must better address the barriers and transitions women experience during pregnancy and postpartum.Item Prevalence, incidence and chronicity of child abuse among orphaned, separated, and street-connected children and adolescents in western Kenya: What is the impact of care environment?(Elsevier, 2023) Ayaya, Samuel; DeLong, Allison; Embleton, Lonnie; Ayuku, David; Sang, Edwin; Hogan, Joseph; Kamanda, Allan; Atwoli, Lukoye; Makori, Dominic; Ott, Mary A.; Ombok, Caroline; Braitstein, Paula; Pediatrics, School of MedicineBackground: The effect of different types of care environment on orphaned and separated children and adolescents' (OSCA) experiences of abuse in sub-Saharan Africa is uncertain. Objective: Our two primary objectives were 1) to compare recent child abuse (physical, emotional, and sexual) between OSCA living in institutional environments and those in family-based care; and 2) to understand how recent child abuse among street-connected children and youth compared to these other vulnerable youth populations. Participants and setting: This project followed a cohort of OSCA in Uasin Gishu County, Kenya (2009-2019). This analysis includes 2393 participants aged 18 years and below, 1017 from institutional environments, 1227 from family-based care, and 95 street-connected participants. Methods: The primary outcome of interest was recent abuse. Multiple logistic regression was used to estimate the odds of recent abuse at baseline, follow-up, and chronically for each abuse domain and adjusted odds ratios (AOR) between care environments, controlling for multiple factors. Results: In total, 47 % of OSCA reported ever experiencing any kind of recent abuse at baseline and 54 % in follow-up. Compared to those in family-based care, street-connected participants had a much higher reported prevalence of all types of recent abuse at baseline (AOR: 5.01, 95 % CI: 2.89, 9.35), in follow-up (AOR: 5.22, 95 % CI: 2.41, 13.98), and over time (AOR: 3.44, 95 % CI: 1.93, 6.45). OSCA in institutional care were no more likely than those in family-based care of reporting any recent abuse at baseline (AOR: 0.85 95 % CI: 0.59-1.17) or incident abuse at follow-up (AOR: 0.91, 95 % CI: 0.61-1.47). Conclusion: OSCA, irrespective of care environment, reported high levels of recent physical, emotional, and sexual abuse. Street-connected participants had the highest prevalence of all kinds of abuse. OSCA living in institutional care did not experience more child abuse than those living in family-based care.Item Retention of HIV-infected and exposed children in a comprehensive HIV clinical care program in Western Kenya(2010-07) Braitstein, Paula; Katshcke, Adrian; Shen, Changyu; Sang, Edwin; Nyandiko, Winstone; Ochieng, Vincent Ooko; Vreeman, Rachel; Yiannoutsos, Constantin; Wools-Kaloustian, Kara; Ayaya, SamwelBackground To describe incidence rates (IR) and risk factors for loss-to-follow-up (LTFU) among HIV-infected and HIV-exposed children in a large HIV treatment programme in Western Kenya. Methods The USAID-AMPATH Partnership has enrolled >100 000 patients (20% children) at 23 clinic sites throughout western Kenya. LTFU is defined as being absent from the clinic for >3 months if on combination antiretroviral treatment (cART) and >6 months if not. Included in this analysis were children aged <14 years, HIV exposed or infected at enrolment, and enrolled between April 2002 and March 2009. The IR for LTFU are presented per 100 child-years (CY) of follow-up. Proportional hazards models with time-independent and time-dependent covariates were used to model factors associated with LTFU. Weight for height Z-scores were calculated using EpiInfo, with severe malnutrition being defined as a Z-score ≤−3.0. Immune suppression was defined as per WHO age-specific categories. Results There were 13 510 children eligible for analysis, comprising 3106 children who at enrolment were HIV infected and 10 404 children who were HIV exposed. The overall IR of LTFU was 18.4 (17.8–18.9) per 100 CY. Among HIV-infected children, 15.2 (13.8–16.7) and 14.1 (13.1–15.8) per 100 CY became LTFU, pre- and post-cART initiation, respectively. The only independent risk factor for becoming LTFU among the HIV-infected children was severe immune suppression (AHR: 2.17, 95% CI: 1.51–3.12). Among the HIV-exposed children, 20.1 per 100 (19.4–20.7) became LTFU. Independent risk factors for LTFU among them were being severely low weight for height (AHR: 1.69, 95% CI: 1.25–2.28), being orphaned at enrolment (AHR: 1.57, 95% CI: 1.23–1.64), being CDC Class B or C (AHR: 1.41, 95% CI: 1.14–1.74), and having received cART (AHR: 1.56, 95% CI: 1.23–1.99). Protective against becoming LTFU among the HIV exposed were testing HIV positive (AHR: 0.26, 95% CI: 0.21–0.32), older age (AHR: 0.90, 95% CI: 0.85–0.96), enrolling in later time periods, and receiving food supplementation (AHR: 0.58, 95% CI: 0.32–1.04). Conclusions There is a high rate of LTFU among these highly vulnerable children, particularly among the HIV exposed. These data suggest that HIV-infected and HIV-exposed children are at especially high risk for LTFU if they are sick or malnourished.Item Trends Over Time for Adolescents Enrolling in HIV Care in Kenya, Tanzania, and Uganda From 2001–2014(Wolters Kluwer, 2018-10) Apondi, Edith; Humphrey, John M.; Sang, Edwin; Mwangi, Ann; Keter, Alfred; Musick, Beverly S.; Nalugoda, Fred K.; Ssali, John; Bukusi, Elizabeth; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara; Ayaya, Samuel; Medicine, School of MedicineBackground: The data needed to understand the characteristics and outcomes, over time, of adolescents enrolling in HIV care in East Africa are limited. Setting: Six HIV care programs in Kenya, Tanzania, and Uganda. Methods: This retrospective cohort study included individuals enrolling in HIV care as younger adolescents (10–14 years) and older adolescents (15–19 years) from 2001–2014. Descriptive statistics were used to compare groups at enrollment and antiretroviral therapy (ART) initiation over time. The proportion of adolescents was compared with the total number of individuals aged 10 years and older enrolling over time. Competing-risk analysis was used to estimate 12-month attrition after enrollment/pre-ART initiation; post-ART attrition was estimated by Kaplan–Meier method. Results: A total of 6344 adolescents enrolled between 2001 and 2014. The proportion of adolescents enrolling among all individuals increased from 2.5% (2001–2004) to 3.9% (2013–2014, P < 0.0001). At enrollment, median CD4 counts in 2001–2004 compared with 2013–2014 increased for younger (188 vs. 379 cells/mm3, P < 0.0001) and older (225 vs. 427 cells/mm3, P < 0.0001) adolescents. At ART initiation, CD4 counts increased for younger (140 vs. 233 cells/mm3, P < 0.0001) and older (64 vs. 323 cells/mm3, P < 0.0001) adolescents. Twelve-month attrition also increased for all adolescents both after enrollment/pre-ART initiation (4.7% vs. 12.0%, P < 0.001) and post-ART initiation (18.7% vs. 31.2%, P < 0.001). Conclusions: Expanding HIV services and ART coverage was likely associated with earlier adolescent enrollment and ART initiation but also with higher attrition rates before and after ART initiation. Interventions are needed to promote retention in care among adolescents.