Treatment of Young Children with HIV Infection: Using Evidence to Inform Policymakers

PMCID: PMC3404108This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Estimating age-based antiretroviral therapy costs for HIV-infected children in resource-limited settings based on World Health Organization weight-based dosing recommendations

Background: Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. Methods: We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0–13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. Results: The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. Conclusions: The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments

World Health Organization Generic Protocol to Assess Drug-Resistant HIV Among Children <18 Months of Age and Newly Diagnosed With HIV in Resource-Limited Countries

Increased use of nonnucleoside reverse transcriptase inhibitors (NNRTIs) in pregnant and breastfeeding women will result in fewer children infected with human immunodeficiency virus (HIV). However, among children infected despite prevention of mother-to-child transmission (PMTCT), a substantial proportion will acquire NNRTI-resistant HIV, potentially compromising response to NNRTI-based antiretroviral therapy (ART). In countries scaling up PMTCT and pediatric ART programs, it is crucial to assess the proportion of young children with drug-resistant HIV to improve health outcomes and support national and global decision making on optimal selection of pediatric first-line ART. This article summarizes a new World Health Organization surveillance protocol to assess resistance using remnant dried blood spot specimens from a representative sample of children aged <18 months being tested for early infant diagnosi

Improving estimates of children living with HIV from the Spectrum AIDS Impact Model

Objective: Estimated numbers of children living with HIV determine programmatic and treatment needs. We explain the changes made to the UNAIDS estimates between 2015 and 2016, and describe the challenges around these estimates. Methods: Estimates of children newly infected, living with HIV, and dying of AIDS are developed by country teams using Spectrum software. Spectrum files are available for 160 countries, which represent 98% of the global population. In 2016, the methods were updated to reflect the latest evidence on mother-to-child HIV transmission and improved assumptions on the age children initiate antiretroviral therapy. We report updated results using the 2016 model and validate these estimates against mother-to-child transmission rates and HIV prevalence from population-based surveys for the survey year. Results: The revised 2016 model estimates 27% fewer children living with HIV in 2014 than the 2015 model, primarily due to changes in the probability of mother-to-child transmission among women with incident HIV during pregnancy. The revised estimates were consistent with population-based surveys of HIV transmission and HIV prevalence among children aged 5–9 years, but were lower than surveys among children aged 10–14 years. Conclusions: The revised 2016 model is an improvement on previous models. Paediatric HIV models will continue to evolve as further improvements are made to the assumptions. Commodities forecasting and programme planning rely on these estimates, and increasing accuracy will be critical to enable effective scale-up and optimal use of resources. Efforts are needed to improve empirical measures of HIV prevalence, incidence, and mortality among children

Viral suppression in adolescents on antiretroviral treatment: review of the literature and critical appraisal of methodological challenges.

OBJECTIVE: Medication adherence is often suboptimal for adolescents with HIV, and establishing correct weight-based antiretroviral therapy dosing is difficult, contributing to virological failure. This review aimed to determine the proportion of adolescents achieving virological suppression after initiating ART. METHODS: MEDLINE, EMBASE and Web of Science databases were searched. Studies published between January 2004 and September 2014 including ≥50 adolescents taking ART and reporting on the proportion of virological suppressed participants were included. RESULTS: From a total of 5316 potentially relevant citations, 20 studies were included. Only eight studies reported the proportion of adolescents that were virologically suppressed at a specified time point. The proportion of adolescents with virological suppression at 12 months ranged from 27 to 89%. CONCLUSION: Adolescent achievement of HIV virological suppression was highly variable. Improved reporting of virological outcomes from a wider range of settings is required to support efforts to improve HIV care and treatment for adolescents

COVID-19 and MIS-C treatment in children—results from an international survey

Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. In addition, access to COVID-19 therapeutics remains limited. Collecting physicians’ experiences with off-label use of therapeutics is important to inform global prioritization processes and better target pediatric research and development. A standardized questionnaire was designed to explore the use of therapeutics used to treat COVID-19 and multisystem inflammatory syndrome in children (MIS-C) in pediatric patients globally. Seventy-three physicians from 29 countries participated. For COVID-19, steroids were used by 75.6% of respondents; remdesivir and monoclonal antibodies were prescribed by 48.6% and 27.1% of respondents, respectively. For MIS-C, steroids were prescribed by 79.1% of respondents and intravenous immunoglobulins by 69.6%. The use of these products depended on their pediatric approval and the limited availability of antivirals and most monoclonal antibodies in Africa, South America, Southeast Asia, and Eastern Europe. Off-label prescription resulted widespread due to the paucity of clinical trials in young children at the time of the survey; though, based on our survey results, it was generally safe and led to clinical benefits. Conclusion: This survey provides a snapshot of current practice for treating pediatric COVID-19 worldwide, informing global prioritization efforts to better target pediatric research and development for COVID-19 therapeutics. Off-label use of such medicines is widespread for the paucity of clinical trials under 12 years and 40 kg, though appears to be safe and generally results in clinical benefits, even in young children. However, access to care, including medicine availability, differs widely globally. Clinical development of COVID-19 antivirals and monoclonal antibodies requires acceleration to ensure pediatric indication and allow worldwide availability of therapeutics that will enable more equitable access to COVID-19 treatment. What is Known: • Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. • Access to care differs widely globally, so because of the diversity of national healthcare systems; the unequal availability of medicines for COVID-19 treatment represents an obstacle to the pediatric population's universal right to health care. What is New: • Off-label COVID-19 drug prescription is widespread due to the lack of clinical trials in children younger than 12 years and weighing less than 40 kg, but relatively safe and generally leading to clinical benefit. • The application of the GAP-f framework to COVID-19 medicines is crucial, ensuring widespread access to all safe and effective drugs, enabling the rapid development of age-appropriate formulations, and developing specific access plans (including stability, storage, packaging, and labeling) for distribution in low- and middle-income countries (LMICs). Antivirals and monoclonal antibodies may benefit from the acceleration to reach widespread and equal diffusion

Community and service provider views to inform the 2013 WHO consolidated antiretroviral guidelines:key findings and lessons learnt

Objective:The objective was to evaluate community and healthcare worker (HCW) values and preferences on key topics to inform the development of the 2013 WHO consolidated guidelines for antiretroviral therapy in low and middle income countries. Design:Cross-sectional e-survey and e-forum discussion; focus group discussions (FGDs) Methods:Data were collected on community perspectives regarding a range of potential clinical and operational recommendations in the 2013 guidelines between November 2012 and January 2013 through an e-survey (n = 1088) and e-forum (n = 955). Additional FGDs were held with people living with HIV (PLHIV) in Malawi and Uganda (n = 88) on antiretroviral therapy (ART) use among pregnant women. Two surveys were also undertaken on similar topics covered in the e-survey for health care workers caring for adults (n = 98) and children (n = 348). Results:There were 1088 e-survey respondents from 117 countries: of whom 37.7% (298/791) were females, 49.9% (431/864) PLHIV, and 20.9% (174/831) from low-income countries. The proportion of e-survey respondents who supported raising the CD4 T-cell threshold for ART initiation in adults from 350 to 500 cells/μl was 51.0% (355/696), and regardless of CD4 T-cell count for all pregnant females 89.8% (607/676), HIV serodiscordant partners 71.9% (486/676), and all children on diagnosis of infection 47.4% (212/447). E-survey respondents strongly supported discontinuing use of stavudine (72.7%, 416/572), task-shifting/sharing from doctors to nurses (75.2%, 275/365) and from nurses to community health workers (71.1%, 261/367) as strategies to expand access to HIV testing, care, and treatment. Focus group discussion respondents identified service capacity, and social and legal concerns as key considerations influencing the decisions of women living with HIV to continue ART after the risk of vertical transmission has passed. Key lessons learnt in these consultations included the need for piloting and validation of questions; sufficient time to adequately disseminate the survey; and consideration of using FGDs and mobile phone technology to improve participation of people with limited internet access. Conclusion:Community participation in guideline development processes is important to ensure that their perspectives are considered in the resulting recommendations. Communities should be actively involved in the adaptation, implementation, and accountability processes related to the guidelines

Modeling of dropwise condensation on flat surfaces

There are two ways for a vapor to condense on a surface: filmwise condensation (FWC) and dropwise condensation (DWC). The interest in DWC is based on the potential increase of the condensation heat transfer coefficient (HTC) by 6 to 10 times compared to the values measured during filmwise condensation. For this reason, several research groups around the world have tried to promote the dropwise condensation and to describe the underneath mechanisms. Such models describe the phenomena that take place during dropwise condensation: the nucleation of a droplet until its departure, the heat exchanged by the drop during its lifetime and the droplets population on the surface. The present paper aims at presenting some of the models developed in the past years which can be used to describe the DWC process. In particular, similarities and differences between the models are highlighted and their predictions are compared against experimental data measured at the Two-phase Heat Transfer Laboratory of the University of Padova.Papers presented at the 13th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Portoroz, Slovenia on 17-19 July 2017 .International centre for heat and mass transfer.American society of thermal and fluids engineers

Patient-reported barriers to adherence to antiretroviral therapy : a systematic review and meta-analysis

Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities.; We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%-45.4%; adolescents 63.1%, 95% CI 46.3%-80.0%; children/caregivers 29.2%, 95% CI 20.1%-38.4%), being away from home (adults 30.4%, 95% CI 25.5%-35.2%; adolescents 40.7%, 95% CI 25.7%-55.6%; children/caregivers 18.5%, 95% CI 10.3%-26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%-35.0%; adolescents 32.4%, 95% CI 0%-75.0%; children/caregivers 26.3%, 95% CI 15.3%-37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%-18.3%; adolescents 25.7%, 95% CI 17.7%-33.6%; children 15.1%, 95% CI 3.9%-26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%-16.1%) and adolescents (28.8%, 95% CI 11.8%-45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%-15.3%; children/caregivers 22.3%, 95% CI 10.2%-34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%-18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%-11.4%). Health service-related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%-21.9%) and stock outs (adults 16.1%, 95% CI 11.7%-20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children.; Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence

The HIV drug optimization agenda: promoting standards for earlier investigation and approvals of antiretroviral drugs for use in adolescents living with HIV.

INTRODUCTION: Most clinical trials for new antiretroviral (ARV) agents are conducted among narrowly defined adult populations. Only after safety and efficacy have been clearly demonstrated among adults living with HIV are trials including adolescents, children and infants conducted. This approach contributes to significant delays in the availability of optimal new ARV regimens for infants, children and adolescents. This commentary discusses issues related to the inclusion of adolescents aged 12 to 18 years in initial HIV clinical phase 3 trials of novel antiretrovirals (ARVs) or conducting parallel phase 3 clinical trials among adolescents. DISCUSSION: The absorption, metabolic and excretion or elimination pathways for drugs do not significantly differ between adolescents and adults. In fact, dosing recommendations for ARVs are the same for adults and adolescents who meet the age and weight criteria. Although conducting clinical trials among adolescents present special challenges (e.g. consenting minors and concerns about trial completion and contraception), these challenges can be addressed to obtain high-quality trial results. Importantly, new agents and optimized combinations have more favourable dosing schedules and side-effect profiles and are more effective ARV agents with higher HIV drug resistance thresholds, which would be extremely beneficial to improve outcomes among HIV-positive adolescents. CONCLUSIONS: Adolescents may not present with significantly different pharmacokinetic characteristics from those in adults. Including HIV-positive adolescents in phase 3 ARV clinical trials, either with adults or in specific adolescent studies conducted in parallel, would allow adolescents to access promising, more effective treatment for HIV years earlier than with the current stepwise approach