Models of lifelong care for children and adolescents with chronic conditions in low-income and middle-income countries: a scoping review.

Globally, non-communicable diseases (NCDs) or chronic conditions account for one-third of disability-adjusted life-years among children and adolescents under the age of 20. Health systems must adapt to respond to the growing burden of NCDs among children and adolescents who are more likely to be marginalised from healthcare access and are at higher risk for poor outcomes. We undertook a review of recent literature on existing models of chronic lifelong care for children and adolescents in low-income and middle-income countries with a variety of NCDs and chronic conditions to summarise common care components, service delivery approaches, resources invested and health outcomes.

Evidence-based service delivery interventions for testing, linking, treating, and retaining children and adolescents living with HIV in primary health care settings: Protocol for a systematic review.

BACKGROUND: At the end of 2019, there were about 2.8 million children and adolescents aged 0-19 living with HIV. In contrast to pregnant women and adults, service delivery for children and adolescents living with HIV continues to lag behind with regard to access to care, components of care delivery, treatment options, and clinical and immunologic outcomes. AIM: The aim of this systematic review is to synthesize the evidence on the most effective interventions, models, programs, and strategies to optimize the delivery of services for the testing, linkage, treatment and retention of children and adolescents living with HIV globally. METHODS: This review protocol is registered at PROSPERO with Registration number: CRD42020209553. The systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). We will use a comprehensive search strategy to search several bibliographic databases including MEDLINE, Embase, CINAHL, Cochrane Library, Global Health, and Psycinfo to identify relevant studies published in the last ten years (2010 to 2020). In addition, we will review cited and citing references of included studies. A pair of reviewers will independently screen titles, abstracts and full texts of articles, extract data from articles meeting inclusion criteria and perform quality assessments of the evidence collected. We will conduct a narrative synthesis of our findings, and if there are sufficient clinically similar studies available, we will conduct meta-analysis using a random-effects model. DISCUSSION: This review will provide evidence on service delivery models that have been evaluated in a range of settings to efficiently and effectively locate, link, treat and retain in care, children and adolescents living with HIV. The synthesized evidence will help guide national governments and health care providers in prioritizing and adopting evidence-based service delivery approaches for children and adolescents living with HIV. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020209553.

Cost-effectiveness of Routine Provider-Initiated Testing and Counseling for Children With Undiagnosed HIV in South Africa.

BACKGROUND: We compared the cost-effectiveness of pediatric provider-initiated HIV testing and counseling (PITC) vs no PITC in a range of clinical care settings in South Africa. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications Pediatric model to simulate a cohort of children, aged 2-10 years, presenting for care in 4 settings (outpatient, malnutrition, inpatient, tuberculosis clinic) with varying prevalence of undiagnosed HIV (1.0%, 15.0%, 17.5%, 50.0%, respectively). We compared "PITC" (routine testing offered to all patients; 97% acceptance and 71% linkage to care after HIV diagnosis) with no PITC. Model outcomes included life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs) from the health care system perspective and the proportion of children with HIV (CWH) diagnosed, on antiretroviral therapy (ART), and virally suppressed. We assumed a threshold of $3200/year of life saved (YLS) to determine cost-effectiveness. Sensitivity analyses varied the age distribution of children seeking care and costs for PITC, HIV care, and ART. RESULTS: PITC improved the proportion of CWH diagnosed (45.2% to 83.2%), on ART (40.8% to 80.4%), and virally suppressed (32.6% to 63.7%) at 1 year in all settings. PITC increased life expectancy by 0.1-0.7 years for children seeking care (including those with and without HIV). In all settings, the ICER of PITC vs no PITC was very similar, ranging from $710 to $1240/YLS. PITC remained cost-effective unless undiagnosed HIV prevalence was <0.2%. CONCLUSIONS: Routine testing improves HIV clinical outcomes and is cost-effective in South Africa if the prevalence of undiagnosed HIV among children exceeds 0.2%. These findings support current recommendations for PITC in outpatient, inpatient, tuberculosis, and malnutrition clinical settings.

Making Implementation Science Work for Children and Adolescents Living With HIV.

The global HIV response is leaving children and adolescents behind. Because of a paucity of studies on treatment and care models for these age groups, there are gaps in our understanding of how best to implement services to improve their health outcomes. Without this evidence, policymakers are left to extrapolate from adult studies, which may not be appropriate, and can lead to inefficiencies in service delivery, hampered uptake, and ineffective mechanisms to support optimal outcomes. Implementation science research seeks to investigate how interventions known to be efficacious in study settings are, or are not, routinely implemented within real-world programmes. Effective implementation science research must be a collaborative effort between government, funding agencies, investigators, and implementers, each playing a key role. Successful implementation science research in children and adolescents requires clearer policies about age of consent for services and research that conform to ethical standards but allow for rational modifications. Implementation research in these age groups also necessitates age-appropriate consultation and engagement of children, adolescents, and their caregivers. Finally, resource, systems, technology, and training must be prioritized to improve the availability and quality of age-/sex-disaggregated data. Implementation science has a clear role to play in facilitating understanding of how the multiple complex barriers to HIV services for children and adolescents prevent effective interventions from reaching more children and adolescents living with HIV, and is well positioned to redress gaps in the HIV response for these age groups. This is truer now more than ever, with urgent and ambitious 2020 global targets on the horizon and insufficient progress in these age groups to date.

Optimal time on HAART for prevention of mother-to-child transmission of HIV.

OBJECTIVES: To determine the impact of time between initiating highly active antiretroviral therapy (HAART) and delivery-duration of antenatal HAART-on perinatal HIV infection. DESIGN: We conducted a retrospective cohort analysis of pregnant HIV-infected women in Lusaka, Zambia. Women in our cohort were receiving HAART and had an infant HIV polymerase chain reaction test between 3 and 12 weeks of life. METHODS: We examined factors associated with infant HIV infection and performed a locally weighted regression analysis to examine the effect of duration of antenatal HAART on perinatal HIV infection. RESULTS: : From January 2007 to March 2010, 1813 HIV-infected pregnant women met inclusion criteria. Mean gestational age at first antenatal visit was 21 weeks (SD ± 6), median CD4+ cell count was 231 cells per microliter (interquartile range: 164-329), and median duration of antenatal HAART was 13 weeks (interquartile range 8-19). Fifty-nine (3.3%) infants were HIV infected. Duration of antenatal HAART was the most important predictor of perinatal HIV transmission. Compared with women initiating HAART at least 13 weeks before delivery, women on HAART for ≤4 weeks had a 5.5-fold increased odds of HIV transmission (95% confidence interval: 2.6 to 11.7). Locally weighted regression analysis suggested limited additional prophylactic benefit beyond 13 weeks on antenatal HAART. CONCLUSIONS: Low rates of mother-to-child HIV transmission can be achieved within programmatic settings in Africa. Maximal effectiveness of prevention of mother-to-child transmission programs is achieved by initiating HAART at least 13 weeks before delivery.

Predictors of CD4 eligibility for antiretroviral therapy initiation among HIV-infected pregnant women in Lusaka, Zambia.

BACKGROUND: In resource-limited settings, CD4 testing is a barrier to antiretroviral therapy initiation in pregnancy. METHODS: We used logistic regression to identify predictors of CD4 cell count ≤ 350 cells/uL in 20,233 pregnant women. RESULTS: The best-performing model included any 3 of: age ≥ 28 years old, hemoglobin ≤ 9.8 g/dL, gestational age ≤ 30 weeks, weight ≤ 64 kg, history of tuberculosis or previous death of an infant prior to one year old. Sensitivity was 45.7% (95% CI: 44.5-47.0), specificity 70.7% (95% CI: 69.6-71.8), and misclassification rate 41.4% (95% CI: 40.5-42.2). CONCLUSION: CD4 triage remains a critical element of maternal HIV care and PMTCT.

Implementation of the Zambia electronic perinatal record system for comprehensive prenatal and delivery care.

OBJECTIVE: To characterize prenatal and delivery care in an urban African setting. METHODS: The Zambia Electronic Perinatal Record System (ZEPRS) was implemented to record demographic characteristics, past medical and obstetric history, prenatal care, and delivery and newborn care for pregnant women across 25 facilities in the Lusaka public health sector. RESULTS: From June 1, 2007, to January 31, 2010, 115552 pregnant women had prenatal and delivery information recorded in ZEPRS. Median gestation age at first prenatal visit was 23weeks (interquartile range [IQR] 19-26). Syphilis screening was documented in 95663 (83%) pregnancies: 2449 (2.6%) women tested positive, of whom 1589 (64.9%) were treated appropriately. 111108 (96%) women agreed to HIV testing, of whom 22% were diagnosed with HIV. Overall, 112813 (98%) of recorded pregnancies resulted in a live birth, and 2739 (2%) in a stillbirth. The median gestational age was 38weeks (IQR 35-40) at delivery; the median birth weight of newborns was 3000g (IQR 2700-3300g). CONCLUSION: The results demonstrate the feasibility of using a comprehensive electronic medical record in an urban African setting, and highlight its important role in ongoing efforts to improve clinical care.

Peripartum nevirapine exposure and subsequent clinical outcomes among HIV-infected women receiving antiretroviral therapy for at least 12 months.

OBJECTIVE: Prior exposure to intrapartum/neonatal nevirapine (NVP) is associated with compromised virologic treatment outcomes once non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is initiated. We examined the longer-term clinical outcomes in a programmatic setting. METHODS: We compared post-12 month mortality and clinical treatment failure (defined by WHO clinical and immunologic criteria) among women with and without prior NVP exposure in Lusaka, Zambia. RESULTS: Between April 2004 and July 2006, 6740 women initiated an NNRTI-containing regimen. At 12 months, 5172 (78%) remained active and were included in this analysis. Of these, 596 (12%) reported prior NVP exposure, whose time from exposure to ART initiation was: <6 months for 11%, 6-12 months for 13%, >12 months for 37%, unknown for 39%. Overall, women with prior NVP exposure trended towards increased survival (adjusted hazard ratio [AHR]: 0.53; 95% confidence interval [CI]: 0.27-1.06, P = 0.07) and towards increased hazard of clinical treatment failure (AHR: 1.18; 95% CI: 0.95-1.47, P = 0.14), particularly those with exposure for <6 months (AHR: 1.52; 95% CI: 0.94-2.45, P = 0.09). CONCLUSIONS: Prior NVP exposure appeared to increase risk for clinical treatment failure after 12 months of follow-up, but this finding did not reach statistical significance. With growing evidence linking recent NVP exposure to virologic failure, optimized monitoring algorithms should be considered for women with starting NNRTI-based ART. The association between prior NVP exposure and improved survival has not been previously shown and may be a result of residual confounding around health-seeking behaviours.