Opportunities for improving the efficiency of paediatric HIV treatment programmes

Objectives: To conduct two economic analyses addressing whether to: routinely monitor HIV-infected children on antiretroviral therapy (ART) clinically or with laboratory tests; continue or stop cotrimoxazole prophylaxis when children become stabilized on ART. Design and methods: The ARROW randomized trial investigated alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in 1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of implementation analyses were undertaken. Scenario analyses investigated whether laboratory monitoring (CD4 tests for efficacy monitoring; haematology/biochemistry for toxicity) could be tailored and targeted to be delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and non-endemic settings. Results: Using all trial data, clinical monitoring delivered similar health outcomes to routine laboratory monitoring, but at a reduced cost, so was cost-effective. Continuing cotrimoxazole improved health outcomes at reduced costs. Restricting routine CD4+ monitoring to after 52 weeks following ART initiation and removing toxicity testing was associated with an incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year (QALY) across all age groups, but was much lower for older children (12+ years at initiation; incremental cost-effectiveness ratio =$769/QALY). Committing resources to improve cotrimoxazole implementation appears cost-effective. A healthcare system that could pay $600/QALY should be willing to spend up to$12.0 per patient-year to ensure continued provision of cotrimoxazole. Conclusion: Clinically driven monitoring of ART is cost-effective in most circumstances. Routine laboratory monitoring is generally not cost-effective at current prices, except possibly CD4 testing amongst adolescents initiating ART. Committing resources to ensure continued provision of cotrimoxazole in health facilities is more likely to represent an efficient use of resources

Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study

Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery

Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences.

The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings

A randomized trial of prolonged co-trimoxazole in HIV-infected children in Africa

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) prophylaxis administered before antiretroviral therapy (ART) reduces morbidity in children infected with the human immunodeficiency virus (HIV). We investigated whether children and adolescents receiving long-term ART in sub-Saharan Africa could discontinue co-trimoxazole

Young HIV-Infected Children and Their Adult Caregivers Prefer Tablets to Syrup Antiretroviral Medications in Africa

Background: Provision of anti-retroviral therapy (ART) for HIV-infected children is complicated using syrup formulations, which are costlier than tablets, harder to transport and store and difficult for health-workers to prescribe and caregivers to administer. Dispersible/crushable tablets may be more appropriate. We studied the acceptability of syrups and scored tablets among young children who used both in the AntiRetroviral Research fOr Watoto (ARROW) trial. Methods: ARROW is an ongoing randomized trial of paediatric ART monitoring and treatment strategies in 1206 children in Uganda and Zimbabwe. 405 children initially received syrups of combination ART including Nevirapine, Zidovudine, Abacavir and Lamivudine before changing, when reaching the 12-,15 kg weightband, to scored adult-dose tablets prescribed according to WHO weightband tables. Caregiver expectations and experiences were collected in questionnaires at their last visit on syrups and after 8 and 24 weeks on tablets. Results: Questionnaires were completed by caregivers of 267 children (median age 2.9 years (IQR 2.5, 3.4)). At last visit on syrups, 79 % caregivers reported problems with syrups, mostly related to number, weight, transportation and conspicuousness of bottles. Difficulties taking tablets were expected by 127(48%) caregivers; however, after 8 and 24 weeks, only 26 % and 18 % reported their children had problems with tablets and no problems were reported with transportation/conspicuousness. Taste, swallowing or vomiting were reported as problems ‘sometimes/often ’ for 14%, 9%

The relationship between leadership style and health worker motivation, job satisfaction and teamwork in Uganda

Conrad Musinguzi,1 Leticia Namale,1 Elizeus Rutebemberwa,2 Aruna Dahal,1 Patricia Nahirya-Ntege,1 Adeodata Kekitiinwa1 1Directorate of Health Systems Strengthening, Baylor College of Medicine Children’s Foundation, Kampala, Uganda; 2Department of Health Policy, Planning and Management, School of Public Health Uganda, College of Health Sciences, Makerere University, Kampala, Uganda Background: Leadership is key to strengthening performance of Health Systems. Leadership styles are important organizational antecedents, especially in influencing employee’s motivation, job satisfaction, and teamwork. There is limited research exploring this relationship among health workers in resource-limited settings such as Uganda. The aim of this study was to examine the relationship between transformational, transactional, and laissez-faire leadership styles and motivation, job satisfaction, and teamwork of health workers in Uganda. Method: We conducted a cross-sectional study in 3 geographic regions of Uganda in November 2015, using self-administered questionnaires with 564 health workers from 228 health facilities. Data were collected on health workers’ perception of leadership styles displayed by their facility leaders, their level of motivation, job satisfaction, and team work. Using Pearson correlation, relationships among variables were identified and associations of the components of leadership styles with motivation, job satisfaction, and teamwork was found using multivariable logistic regression. Results: Health workers in Uganda preferred leaders who were transformational (62%) compared with being transactional (42%) or laissez-faire (14%). Transformational leadership was positively correlated with motivation (r=0.32), job satisfaction (r=0.38), and team work (r=0.48), while transactional leadership was positively correlated with job satisfaction (r=0.21) and teamwork (r=0.18). Motivation was positively associated with leaders who displayed idealized influence-behavior (odds ratio [OR]=3.7; 95% CI, 1.33–10.48) and intellectual stimulation (OR=2.4; 95% CI, 1.13–5.15) but negatively associated with management by exception (OR=0.4; 95% CI, 0.19–0.82). Job satisfaction was positively associated with intellectual stimulation (OR=5.7; 95% CI, 1.83–17.79). Teamwork was positively associated with idealized influence-behavior (OR=1.07–8.57), idealized influence-attributed (OR=3.9; 95% CI, 1.24–12.36), and contingent reward (OR=5.6; 95% CI, 1.87–17.01). Conclusion: Transformational styles had a positive impact on stimulating motivation, assuring job satisfaction, and consolidating teamwork among health workers compared with those who demonstrated transactional skills or laissez-faire styles. Recommendation: Supporting transformational leadership skills development in health facility leaders could encourage health worker motivation, strengthen job satisfaction, and maintain cohesion among health workers for better service delivery. Keywords: transformational leadership, transactional leadership, laissez-faire leadership, motivation, job satisfaction, teamwor

Prevalence and correlates of HIV testing among adolescents 10–19 years in a post-conflict pastoralist community of Karamoja region, Uganda

Abstract Background Adolescents are a priority group in HIV prevention and treatment. This study sought to determine the prevalence and correlates of HIV testing services (HTS) among adolescents in the pastoralist post-conflict area of Karamoja sub region, Uganda. Methods A cross sectional study of 1439 adolescents aged 10–19 years, attending nine public health facilities in five of the seven districts of Karamoja, was conducted between August to September 2016. Adolescents were consecutively selected and interviewed using structured interviewer administered questionnaires. All respondents who had never tested for HIV were offered HTS. The main outcome was ever tested for HIV. Correlates of ever tested were analysed using multivariate logistic regression model. Results Of the 1439 adolescents, 904 (62.8%) were females, 1203 (83.6%) were aged 15–19 years, 618 (43.0%) had attained primary education and 885 (61.5%) had ever had sex. Overall 1177 (81.8%) had ever tested and received HIV results. Older age (15–19 years) (adj.OR = 2.71, 95% CI: 1.85–3.96), secondary level education or higher (adj.OR = 2.33, 95% CI: 1.33–4.10), and ever had sex (adj.OR = 2.03, 95% CI: 1.42–2.90) were associated with higher odds of HIV testing. Of the 262 who had never tested, 169 (64.5%) accepted testing and 2.4% were HIV positive. Reasons for not accepting the test included fear of being tested and not ready for an HIV test because of perceived suffering HIV positive clients go through. Conclusion Awareness of HIV status and uptake of HTS among adolescents in this hard-to-reach post-conflict region was high and close to the global UNAIDS target of 90%. However, the HIV prevalence of 2.4% among the non-testers who accepted to be tested was high and emphasises the need for targeted testing to reach the undiagnosed HIV infected adolescents in this region

Single-dose nevirapine exposure does not affect response to antiretroviral therapy in HIV-infected African children aged below 3 years.

OBJECTIVES: To assess the impact of exposure to single-dose nevirapine (sdNVP) on virological response in young Ugandan/Zimbabwean children (<3 years) initiating antiretroviral therapy (ART), and to investigate other predictors of response. DESIGN: Observational analysis within the ARROW randomized trial. METHODS: sdNVP exposure was ascertained by the caregiver's self-report when the child initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Viral load was assayed retrospectively over a median 4.1 years of follow-up. Multivariable logistic regression models were used to identify independent predictors of viral load below 80 copies/ml, 48 and 144 weeks after ART initiation (backwards elimination, exit P = 0.1). RESULTS: Median (IQR) age at ART initiation was 17 (10-23) months in 78 sdNVP-exposed children vs. 21 (14-27) months in 289 non-exposed children (36 vs. 20% <12 months). At week 48, 49 of 73 (67%) sdNVP-exposed and 154 of 272 (57%) non-exposed children had viral load below 80 copies/ml [adjusted odds ratio (aOR) 2.34 (1.26-4.34), P = 0.007]; 79 and 77% had viral load below 400 copies/ml. Suppression was significantly lower in males (P = 0.009), those with higher pre-ART viral load (P = 0.001), taking syrups (P = 0.05) and with lower self-reported adherence (P = 0.04). At week 144, 55 of 73 (75%) exposed and 188 of 272 (69%) non-exposed children had less than 80 copies/ml [aOR 1.75 (0.93-3.29), P = 0.08]. There was no difference between children with and without previous sdNVP exposure in intermediate/high-level resistance to NRTIs (P > 0.3) or NNRTIs (P > 0.1) (n = 88) at week 144. CONCLUSION: Given the limited global availability of lopinavir/ritonavir, its significant formulation challenges in young children, and the significant paediatric treatment gap, tablet fixed-dose-combination NVP-based ART remains a good alternative to syrup lopinavir-based ART for children, particularly those over 1 year and even if exposed to sdNVP.This is an open access article distributed under the Creative Commons Attribution-Non Commercial License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0

Pubertal development in HIV-infected African children on first-line antiretroviral therapy.

OBJECTIVES: To estimate age at attaining Tanner stages in Ugandan/Zimbabwean HIV-infected children initiating antiretroviral therapy (ART) in older childhood and investigate predictors of delayed puberty, particularly age at ART initiation. DESIGN: Observational analysis within a randomized trial. METHODS: Tanner staging was assessed every 24 weeks from 10 years of age, menarche every 12 weeks and height every 4-6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering predictors using multivariable regression. Growth was estimated using multilevel models with child-specific intercepts and trajectories. RESULTS: Median age at ART initiation was 9.4 years (inter-quartile range 7.8, 11.3) (n = 582). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (P < 0.05) and menarche (P = 0.02); in boys the delaying effect generally weakened with older age. There were additional significant delays associated with greater impairments in pre-ART height-for-age Z-score (P < 0.05) in both sexes and pre-ART BMI-for-age in girls (P < 0.05). There was no evidence that pre-ART immuno-suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and were still significantly increasing their height when in Tanner stage 5 (P < 0.01). CONCLUSION: Delaying ART initiation until older childhood substantially delays pubertal development and menarche, independently of immuno-suppression. This highlights that factors other than CD4, such as pubertal development, need consideration when making decisions about timing of ART initiation in older children