Winstone M. Nyandiko

A systematic review of pediatric adherence to antiretroviral therapy in low- and middle-income countries.

Background: Sustaining antiretroviral therapy (ART) adherence requires accurate, consistent monitoring, a particular challenge for low-income countries. The optimal strategy to measure pediatric adherence remains unclear. Objective: To conduct a systematic review of pediatric ART adherence measurement techniques, adherence estimates, and clinical correlates in low- and middle-income countries to inform ART adherence monitoring. Methods: We searched online bibliographic databases, including MEDLINE and EMBASE, using systematic criteria. Two reviewers selected all descriptive or interventional studies involving nonpregnant, HIV-positive individuals ≤18 years old that measured ART adherence in low- or middle-income countries as defined by World Bank criteria. Data were extracted regarding sample characteristics, study setting, measurement strategy, adherence estimate, and adherence correlates. Results: The search yielded 1566 titles, of which 17 met selection criteria. Adherence measurement strategies included self- or proxy-report measures (14 studies), pill counts (4 studies), pharmacy records, drug levels, clinic adherence, and directly observed therapy (1 study each). The self- or proxy-report measures were heterogeneous, and few employed validation strategies. Caregiver-reported adherence was generally higher than self-report estimates. Pill counts revealed lower adherence estimates. Estimates of ART adherence ranged from 49% to 100%, with 76% of articles reporting >75% adherence. Factors related to family structure, socioeconomic status, disclosure, and medication regimen were all significantly associated with ART adherence. Conclusions: Pediatric HIV care programs in low- and middle-income countries use heterogeneous methods to measure ART adherence. Adherence estimates vary substantially, but most studies from low- and middle-income countries report >75% adherence, whereas most studies from high-income countries report <75% adherence.

An electronic medical record system for ambulatory care of HIV-infected patients in Kenya

Administering and monitoring therapy is crucial to the battle against HIV/AIDS in sub-Saharan Africa. Electronic medical records (EMRs) can aid in documenting care, monitoring drug adherence and response to therapy, and providing data for quality improvement and research. Faculty at Moi University in Kenya and Indiana and University in the USA opened adult and pediatric HIV clinics in a national referral hospital, a district hospital, and six rural health centers in western Kenya using a newly developed EMR to support comprehensive outpatient HIV/AIDS care. Demographic, clinical, and HIV risk data, diagnostic test results, and treatment information are recorded on paper encounter forms and hand-entered into a central database that prints summary flowsheets and reminders for appropriate testing and treatment. There are separate modules for monitoring the Antenatal Clinic and Pharmacy. The EMR was designed with input from clinicians who understand the local community and constraints of providing care in resource poor settings. To date, the EMR contains more than 30,000 visit records for more than 4000 patients, almost half taking antiretroviral drugs. We describe the development and structure of this EMR and plans for future development that include wireless connections, tablet computers, and migration to a Web-based platform.

Disclosure of HIV status to children in resource-limited settings: a systematic review

Informing 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.

Outcomes of HIV-infected orphaned and non-orphaned children on antiretroviral therapy in western Kenya

Objectives:Determine outcome differences between orphaned and non-orphaned children receiving antiretroviral therapy (ART). Design:Retrospective review of prospectively recorded electronic data. Setting:Nine HIV clinics in western Kenya. Population:279 children on ART enrolled between August 2002 and February 2005. Main Measures:Orphan status, CD4%, sex- and age-adjusted height (HAZ) and weight (WAZ) z scores, ART adherence, mortality. Results:Median follow-up was 34 months. Cohort included 51% males and 54% orphans. At ART initiation (baseline), 71% of children had CDC clinical stage B or C disease. Median CD4% was 9% and increased dramatically the first 30 weeks of therapy, then leveled off. Parents and guardians reported perfect adherence at every visit for 75% of children. Adherence and orphan status were not significantly associated with CD4% response. Adjusted for baseline age, follow-up was significantly shorter among orphaned children (median 33 vs. 41 weeks, P = 0.096). One-year mortality was 7.1% for orphaned and 6.6% for non-orphaned children (P = 0.836). HAZ and WAZ were significantly below norm in both groups. With ART, HAZ remained stable, while WAZ tended to increase toward the norm, especially among non-orphans. Orphans showed identical weight gains as non-orphans the first 70 weeks after start of ART but experienced reductions afterwards. Conclusions:Good ART adherence is possible in western rural Kenya. ART for HIV-infected children produced substantial and sustainable CD4% improvement. Orphan status was not associated with worse short-term outcomes but may be a factor for long-term therapy response. ART alone may not be sufficient to reverse significant developmental lags in the HIV-positive pediatric population.

‘Wamepotea’ (They have become lost): Outcomes of HIV-positive and HIV-exposed children lost to follow-up from a large HIV treatment program in western Kenya

Objective:The objective of this study was to identify the vital status and reasons for children becoming loss to follow-up (LTFU) from a large program in western Kenya. Methods:This was a prospective evaluation of a random sample of 30% of HIV-exposed and HIV-positive children LTFU from either an urban or rural HIV Academic Model Providing Access to Healthcare clinic. LTFU is defined as absence from clinic for >6 months if on combination antiretroviral therapy and > 12 months if not. Experienced community health workers were engaged to locate them. Results:There were 97 children sampled (78 urban, 19 rural). Of these, 82% were located (78% urban, 100% rural). Among the HIV positive, 16% of the children were deceased, and 16% had not returned to clinic because of disclosure issues/discrimination in the family or community. Among the HIV exposed, 30% never returned to care because their guardians either had not disclosed their own HIV status or were afraid of family/community stigma related to their HIV status or that of the child. Among children whose HIV status was unknown, 29% of those found had actually died, and disclosure/discrimination accounted for 14% of the reasons for becoming LTFU. Other reasons included believing the child was healed by faith or through the use of traditional medicine (7%), transport costs (6%), and transferring care to other programs or clinics (8%). Conclusion:After locating >80% of the children in our sample, we identified that mortality and disclosure issues including fear of family or community discrimination were the most important reasons why these children became LTFU.

Outcomes of HIV-exposed children in western Kenya: efficacy of prevention of mother to child transmission in a resource-constrained setting.

Objectives:To compare rates of mother to child transmission of HIV and infant survival in women-infant dyads receiving different interventions in a prevention of Mother to Child Transmission (pMTCT) program in western Kenya. Design:Retrospective cohort study using prospectively collected data stored in an electronic medical record system. Setting:Eighteen HIV clinics in western Kenya. Population:HIV-exposed infants enrolled between February 2002 and July 2007, at any of the United States Agency for International Development-Academic Model Providing Access To Healthcare partnership clinics. Main outcome measures:Combined endpoint (CE) of infant HIV status and mortality at 3 and 18 months. Analysis:Descriptive statistics, χ2 Fisher exact test, and multivariable modeling. Results:Between February 2002 and July 2007, 2477 HIV-exposed children were registered for care by the United States Agency for International Development-Academic Model Providing Access To Healthcare partnership pMTCT program before 3 months of age. Median age at enrollment was 6.1 weeks; 50.4% infants were male. By 3 months, 31 of 2477 infants (1.3%) were dead and 183 (7.4%) were lost to follow-up. One thousand (40%) underwent HIV DNA Polymerase Chain Reaction virologic test at a median age of 8.3 weeks: 5% were HIV infected, 89% uninfected, and 6% were indeterminate. Of the 968 infants with specific test results or mortality data at 3 months, the CE of HIV infection or death was reached in 84 of 968 (8.7%) infants. The 3-month CE was significantly impacted (A) by maternal prophylaxis [51 of 752 (6.8%) combination antiretroviral therapy (cART); 8 of 69 (11.6%) single-dose nevirapine (sdNVP); and 25 of 147 (17%) no prophylaxis (P < 0.001)] and (B) by feeding method for the 889 of 968 (91.8%) mother-infant pairs for which feeding choice was documented [5 of 29 (17.2%) exclusive breastfeeding; 13 of 110 (11.8%) mixed feeding; and 54 of 750 (7.2%) formula feeding (P = 0.041)]. Of the 1201 infants ≥18 months of age: 41 (3.4%) were deceased and 329 (27.4%) were lost to follow-up. Of 621 of 831 (74.7%) infants tested, 65 (10.5%) were infected resulting in a CE of 103 of 659 (15.6%). CE differed significantly by maternal prophylaxis [52 of 441 (11.8%) for cART; 13 of 96 (13.5%) for sdNVP; and 38 of 122 (31.2%) no therapy group (P < 0.001)] but not by feeding method for the 638 of 659 (96.8%) children with documented feeding choice [7 of 35 (20%) exclusive breastfeeding, 14 of 63 (22.2%) mixed, and 74 of 540 (13.7%) formula (P = 0.131)]. On multivariate analysis, sdNVP (odds ratio: 0.4; 95% confidence interval: 0.2 to 0.8) and cART (odds ratio: 0.3; 95% confidence interval: 0.2 to 0.6) were associated with fewer CE. At 18 months, feeding method was not significantly associated with the CE. Conclusions:Though ascertainment bias is likely, results strongly suggest a benefit of antiretroviral prophylaxis in reducing infant death and HIV infection, but do not show a benefit at 18-months from the use of formula. There was a high rate of loss to follow up, and adherence to the HIV infant testing protocol was less than 50% indicating the need to address barriers related to infant HIV testing, and to improve outreach and follow-up services.

Association of antiretroviral and clinic adherence with orphan status among HIV-infected children in Western Kenya.

Background:Pediatric adherence to antiretroviral therapy (ART) is not well studied in resource-limited settings. Reported ART adherence may be influenced by contextual factors, such as orphan status. Objectives:The objectives of this study were to describe self- and proxy-reported pediatric ART adherence in a resource-limited population and to investigate associated contextual factors. Patients and Methods:This was a retrospective study involving pediatric, HIV-infected patients in Western Kenya. We included patients aged 0-14 years, who were on ART and had at least 1 adherence measurement (N = 1516). We performed logistic regression to assess the association between orphan status and odds of imperfect adherence, adjusting for sex, age, clinic site, number of adherence measures, and ART duration, stratified by age and ART duration. Results:Of the 1516 children, only 33% had both parents living when they started ART. Twenty-one percent had only father dead, 28% had only mother dead, and 18% had both parents dead. Twenty-nine percent reported imperfect ART adherence. The odds of ART nonadherence increase for children with both parents dead. Fifty-seven percent of children had imperfect clinic adherence. There was no significant association between orphan status and imperfect clinic adherence. Conclusions:The majority of pediatric patients in this resource-limited setting maintained perfect ART adherence, though only half kept all scheduled clinic appointments. Understanding contextual factors, such as orphan status, will strengthen adherence interventions.

Factors Sustaining Pediatric Adherence to Antiretroviral Therapy in Western Kenya

Antiretroviral therapy (ART) requires nearly perfect adherence to be effective. Although 90% of HIV-infected children live in Africa, there are limited data on pediatric adherence from this multicultural continent.We conducted a qualitative study to identify key factors contributing to pediatric ART adherence. Ten focus group discussions (N = 85) and 35 individual interviews were conducted with parents and guardians of HIV-infected children receiving ART in western Kenya. Interviews covered multiple aspects of the experience of having children take ART and factors that inhibited or facilitated medication adherence. Constant comparison, progressive coding, and triangulation methods were used to arrive at a culturally contextualized, conceptual model for pediatric ART adherence derived from the descriptions of the lived experience in this resource-limited setting. Child care, including sustained ART adherence, depends on interacting cultural and environmental determinants at the levels of the individual child, parent/caregiver, household, community, health care system, and society.

The clinical burden of tuberculosis among human immunodeficiency virus-infected children in Western Kenya and the impact of combination antiretroviral treatment.

Context: The burden of tuberculosis (TB) disease in children, particularly in HIV-infected children, is poorly described because of a lack of effective diagnostic tests and the emphasis of public health programs on transmissible TB. Objectives: The objectives of this study were to describe the observed incidence of and risk factors for TB diagnosis among HIV-infected children enrolled in a large network of HIV clinics in western Kenya. Design: Retrospective observational study. Setting: The USAID-Academic Model Providing Access to Healthcare (AMPATH) Partnership is Kenya’s largest HIV/AIDS care system. Since 2001, the program has enrolled over 70,000 HIV-infected patients in 18 clinics throughout Western Kenya. Patients: This analysis included all HIV-infected children aged 0 to 13 years attending an AMPATH clinic. Main Outcome Measure: The primary outcome was a diagnosis of any TB, defined either by a recorded diagnosis or by the initiation of anti-TB treatment. Diagnosis of TB is based on a modified Kenneth Jones scoring system and is consistent with WHO case definitions. Results: There were 6535 HIV-infected children aged 0 to 13 years, eligible for analysis, 50.1% were female. Of these, 234 (3.6%) were diagnosed with TB at enrollment. There were subsequently 765 new TB diagnoses in 4368.0 child-years of follow-up for an incidence rate of 17.5 diagnoses (16.3–18.8) per 100 child-years. The majority of these occurred in the first 6 months after enrollment (IR: 106.8 per 100 CY, 98.4–115.8). In multivariable analysis, being severely immune-suppressed at enrollment (Adjusted Hazard Ratio [AHR]: 4.44, 95% CI: 3.62–5.44), having ever attended school AHR: 2.65, 95% CI: 2.15–3.25), being an orphan (AHR: 1.57, 95% CI: 1.28–1.92), being severely low weight-for-height at enrollment (AHR: 1.46, 95% CI: 1.32–1.62), and attending an urban clinic (AHR: 1.39, 95% CI: 1.16–1.67) were all independent risk factors for having an incident TB diagnosis. Children receiving combination antiretroviral treatment were dramatically less likely to be diagnosed with incident TB (AHR: 0.15, 95% CI: 0.12–0.20). Conclusions: These data suggest a high rate of TB diagnosis among HIV-infected children, with severe immune suppression, school attendance, orphan status, very low weight-for-height, and attending an urban clinic being key risk factors. The use of combination antiretroviral treatment reduced the probability of an HIV-infected child being diagnosed with incident TB by 85%.

A Cross-Sectional Study of Disclosure of HIV Status to Children and Adolescents in Western Kenya

Introduction Disclosure of HIV status to children is essential for disease management but is not well characterized in resource-limited settings. This study aimed to describe the prevalence of disclosure and associated factors among a cohort of HIV-infected children and adolescents in Kenya. Methods We conducted a cross-sectional study, randomly sampling HIV-infected children ages 6–14 years attending 4 HIV clinics in western Kenya. Data were collected from questionnaires administered by clinicians to children and their caregivers, supplemented with chart review. Descriptive statistics and disclosure prevalence were calculated. Univariate analyses and multivariate logistic regression were performed to assess the association between disclosure and key child-level demographic, clinical and psychosocial characteristics. Results Among 792 caregiver-child dyads, mean age of the children was 9.7 years (SD = 2.6) and 51% were female. Prevalence of disclosure was 26% and varied significantly by age; while 62% of 14-year-olds knew their status, only 42% of 11-year-olds and 21% of 8-year-olds knew. In multivariate regression, older age (OR 1.49, 95%CI 1.35–1.63), taking antiretroviral drugs (OR 2.27, 95%CI 1.29–3.97), and caregiver-reported depression symptoms (OR 2.63, 95%CI 1.12–6.20) were significantly associated with knowing one’s status. Treatment site was associated with disclosure for children attending one of the rural clinics compared to the urban clinic (OR 3.44, 95%CI 1.75–6.76). Conclusions Few HIV-infected children in Kenya know their HIV status. The likelihood of disclosure is associated with clinical and psychosocial factors. More data are needed on the process of disclosure and its impact on children.