Management Of HIV-infected Children Research Articles

Causes of death in HIV-infected and HIV-uninfected children aged under-five years in western Kenya.

Describe the causes of death among infants and children less than 5 years stratified by HIV status. Cross-sectional analysis of causes of death ascertained through minimally invasive tissue sampling (MITS) in the Kenya Child Health and Mortality Prevention Surveillance site. We included decedents aged 28 days to less than 5 years, whose death was reported within 36 h, underwent MITS, and had HIV test results and causes of death determined. MITS specimens were tested using Taqman Array Cards, culture, cytology, histopathology and immunohistochemistry and HIV PCR. A panel evaluated epidemiologic, clinical, verbal autopsy and laboratory data to assign causes of death using ICD-10 guidelines. Causes of death and etiological agents were stratified by HIV status. Of 176 included decedents, 14% (n = 25) were HIV-infected, median viral load was 112 205 copies/ml [interquartile range (IQR) = 9349-2 670 143). HIV-disease (96%; n = 24) and malnutrition (23%; n = 34) were the leading underlying causes of death in HIV-infected and HIV-uninfected decedents, respectively. Malnutrition was more frequent in the causal chain of HIV-infected (56%; n = 14) than HIV-uninfected decedents (31%; n = 49) (P value = 0.03). Viral pneumonia was twice as common in HIV-infected (50%; n = 9) than HIV-uninfected decedents (22%; n = 7) (P value = 0.04). Nearly all HIV-infected decedents' underlying cause of death was HIV disease, which was associated with malnutrition. Our findings underscore the need for strengthening early identification and management of HIV-infected children. Prevention, early diagnosis and treatment of malnutrition could be instrumental in improving the survival of HIV-infected and HIV-uninfected children.

Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018.

Background: Combined antiretroviral therapy (cART) has been associated with a steep decrease in mortality and morbidity in HIV-1 infected children. New antiretroviral molecules and drug classes have been developed and the management of HIV-infected children has improved, but recent data on survival are limited.Methods: An observational retrospective study investigating changes in mortality and morbidity was conducted on 1,091 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018.Results: Three hundred and fifty-four (32%) AIDS events and 26 (2%) deaths occurred overtime. Mortality rates decreased from 0.4/100 person-years in 2001–2006 to 0.27/100 person-years in 2007–2012 and 0.07/100 person-years in 2013–2018. Notably, 92% of the dead children were born in Italy, but only 50% were followed-up since birth or within three months of age. Seventy three percent of children had started cART at age ≥6 months; 23% were treated for <30 days before death. B and C clinical events progressively decreased (P < 0.0001). Opportunistic infections significantly decreased over time, but still were the most common events in all the periods (6.76/100 person-years in 2013–2018). In the last period, severe bacterial infections were the most common ones. Cancer rates were 0.07/100; 0.17/100; 0.07/100 person-years in the three periods, respectively.Conclusions: Progressive reductions both in mortality and in rates of class B and C clinical events and OIs have been observed during the cART era. However, deaths were still registered; more than half of dead children were enrolled after birth and had belatedly started cART.

First-line antiretroviral drug discontinuations in children.

IntroductionThere are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.MethodsWe included children (<16 years at ART initiation) who initiated ≥3 antiretrovirals between 2004–2014 with ≥1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity.ResultsWe included 3579 children with median follow-up duration of 41 months (IQR 14–72). At ART initiation, median age was 44 months (IQR 13–89) and median CD4 percent was 15% (IQR 9–21%). At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%), treatment failure (18%), treatment simplification (5%), drug interactions (3%), and other or unspecified reasons (18%). The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2–55.4), 1.6 (0.5–4.8), 2.0 (1.2–3.3), and 1.3 (0.6–2.8) per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively.ConclusionsWhile stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health Organization recommendation to replace stavudine with abacavir or zidovudine in paediatric first-line ART regimens in order to improve paediatric first-line ART durability.

Antiretroviral Stewardship in a Pediatric HIV Clinic: Development, Implementation and Improved Clinical Outcomes.

Antiretroviral (ARV) management in pediatrics is a challenging process in which multiple barriers to optimal therapy can lead to poor clinical outcomes. In a pediatric HIV clinic, we implemented a systematic ARV stewardship program to evaluate ARV regimens and make recommendations for optimization when indicated. A comprehensive assessment tool was used to screen for issues related to genotypic resistance, virologic/immunologic response, drug-drug interactions, side effects and potential for regimen simplification. The ARV stewardship team (AST) made recommendations to the HIV clinic provider, and followed patients prospectively to assess clinical outcomes at 6 and 12 months. The most common interventions made by the AST included regimen optimization in patients on suboptimal regimens based on resistance mutations (35.4%), switching to safer ARVs (33.3%) and averting significant drug-drug interactions (10.4%). In patients anticipated to have a change in viral load (VL) as a result of the AST recommendations, we identified a significant benefit in virologic outcomes at 6 and 12 months when recommendations were implemented within 6 months of ARV review. Patients who had recommendations implemented within 6 months had a 7-fold higher probability of achieving a 0.7 log10 reduction in VL by 6 months, and this benefit remained significant after controlling for adherence [adjusted odds ratio: 6.8 (95% confidence interval: 1.03-44.9; P <0.05)]. A systematic ARV stewardship program implemented at a pediatric HIV clinic significantly improved clinical outcomes. ARV stewardship programs can be considered a core strategy for continuous quality improvement in the management of HIV-infected children and adolescents.

NOVEL APP FOR PRACTICAL DOSING OF COMBINATION ANTIRETROVIRAL THERAPY IN PEDIATRIC PATIENTS WITH HIV/AIDS

BackgroundCombination antiretroviral therapy (ART) of HIV infection in pediatric patients requires lifetime daily administration of a minimum of three antiretroviral drugs (ARVs). A wide range of dosing regimens is used in these patients. Dosing errors are common and may result in ARVs overdosing with associated toxicities orARVs underdosing resulting in the development of viral resistance. Attempts have been made to produce compact ARVs dosing charts, but have not been successful due to the complexity of regimens, ARV drug-drug interactions and compatibility restrictions. Advances in mobile technology have brought new opportunities for creating dosing support tools, including smartphone applications (Apps). In middle and low income countries, most affected by HIV epidemic,smartphones and tablets are widespread among medicalprofessionals. A mobile Appthat produces correct pediatric ARVs dosing, warnings for compatibility and most important drug interactions,has the potential to significantly improve the quality of ART in HIV-infected children.MethodsUsing reference ARVs guidelines from the 2014 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection by the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children and 2013 World Health Organization pediatric HIV treatment guidelines we have developed a novel drug prescription App for pediatric ART.ResultsA noveldrug prescription App, based on up to date references, permits health care providers to easily access up-to-date dosing information and quickly calculate individualdoses of all ARVsbased on a patient's characteristics (e.g. weight, height, age, serum creatinine value). Most importantly, the App can be easily updated and synchronized remotely, allowing for timelydelivery of most important pediatric ARVs dosing updates.ConclusionThe smartphone App for pediatric ARVs can serve as an important healthcare worker support tool in the treatment of HIV-infected infants and children. Pharmacometric modelingcan be built in such App to leverage resistance and clinical patient data, individualize dosing strategies particularly for co-morbidities and optimize ART outcome. Most importantly, in the era of the global scale up of pediatric ART and task shifting of ART management to nursing staff, this App can have significant capacitating effect on the healthcare workforce.

Nutritional Supplementation in HIV-Infected Children: A Review

The nutritional status of HIV-infected children in terms of anthropometric indices and micronutrient concentrations is commonly compromised. Malnutrition is a risk factor for mortality at initiation of highly active antiretroviral therapy (HAART). The role of HAART is pivotal in the management of HIV-infected children. Treatment with HAART has been shown to decrease mortality and improve CD4 counts and reduce viral load

Text messages as a learning tool for midwives

The use of cell phone text messaging to improve access to continuing healthcare education in under-resourced settings is not well documented. We aimed to assess whether this method of education is acceptable to South African midwives in both the public and private sectors. Essential healthcare lessons from the Maternal Care book of the Perinatal Education Programme (PEP) were delivered via text message to more than 2 500 midwives each week for a period of 6 months. Each message concluded with a link to a website, where additional information about each lesson could be accessed. Results of a survey, conducted with 50 of the message recipients, demonstrated that the text messages were well received by the midwives; the information was widely shared with colleagues and was believed to improve learning and patient care. Lack of access to the internet, or failure to utilise this facility to obtain additional information, indicated that limitations still exist in internet-based distance education, especially in the public sector. The use of text messaging promises to provide cost-effective learning opportunities, and improve a wide range of clinical services, such as the management of HIV-infected children and adults.

Management of HIV-infected children in Africa: progress and challenges

Over the past three decades HIV has caused significant morbidity and mortality among children, with sub-Saharan Africa bearing the brunt of the epidemic.1 Of the estimated 33 million people living...

Development of a clinical algorithm to prioritise HIV testing of hospitalised paediatric patients in a low resource moderate prevalence setting

ObjectiveTo develop a clinical algorithm to identify paediatric patients who should be offered HIV testing in a setting of moderate HIV prevalence and limited resources.MethodsIn a prospective cross-sectional study at...

Antiretroviral Therapy in HIV-Infected Infants and Children

Antiretroviral (ARV) therapy in human immunodeficiency virus(HIV)-infected infants and children has changed dramatically over the past several years, from monotherapy in the 1990s to the current use of combination regimens, including highly active ARV therapy (HAART). HAART has been associated with increased survival, reduction in opportunistic infections, improved growth and neurocognitive function, and improved quality of life. The goal of HAART is to achieve maximal suppression of viral replication to prevent disease progression, preserve immunologic function, and reduce the development of resistance while minimizing therapy-related side effects. A total of 16 ARV drugs have an approved pediatric treatment indication and are available as a pediatric formulation, tablet, or capsule size as of February 2009 (Table 1). ARV treatment options are continually being updated because of availability of new medications, formulations, and dosing recommendations. Although this review summarizes the current information, US readers should refer to the Working Group Guidelines on Antiretroviral Therapy and Medical Management of HIV-Infected Children for details, including the evidence basis for the treatment recommendations and future updates. International readers should refer to the World Health Organization and Pediatric European Network for Treatment of acquired immunodeficiency syndrome guidelines as well as locally applicable national and regional guidelines.

British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children

SUMMARY AND KEY RECOMMENDATIONS: The aim of these guidelines is to describe a practical but evidence-based approach to the diagnosis and treatment of central nervous system tuberculosis in children and adults. We have presented guidance on tuberculous meningitis (TBM), intra-cerebral tuberculoma without meningitis, and tuberculosis affecting the spinal cord. Our key recommendations are as follows: 1. TBM is a medical emergency. Treatment delay is strongly associated with death and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of TBM is suspected. Do not wait for microbiological or molecular diagnostic confirmation. 2. The diagnosis of TBM is best made with lumbar puncture and examination of the cerebrospinal fluid (CSF). Suspect TBM if there is a CSF leucocytosis (predominantly lymphocytes), the CSF protein is raised, and the CSF:plasma glucose is <50%. The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with the volume of CSF submitted; repeat the lumbar puncture if the diagnosis remains uncertain. 3. Imaging is essential for the diagnosis of cerebral tuberculoma and tuberculosis involving the spinal cord, although the radiological appearances do not confirm the diagnosis. A tissue diagnosis (by histopathology and mycobacterial culture) should be attempted whenever possible, either by biopsy of the lesion itself, or through diagnostic sampling from extra-neural sites of disease e.g. lung, gastric fluid, lymph nodes, liver, bone marrow. 4. Treatment for all forms of CNS tuberculosis should consist of 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months followed by 2 drugs (isoniazid, rifampicin) for at least 10 months. Adjunctive corticosteroids (either dexamethasone or prednisolone) should be given to all patients with TBM, regardless of disease severity. 5. Children with CNS tuberculosis should ideally be managed by a paediatrician with familiarity and expertise in paediatric tuberculosis or otherwise with input from a paediatric infectious diseases unit. The Children's HIV Association of UK and Ireland (CHIVA) provide further guidance on the management of HIV-infected children (www.chiva.org.uk). 6. All patients with suspected or proven tuberculosis should be offered testing for HIV infection. The principles of CNS tuberculosis diagnosis and treatment are the same for HIV infected and uninfected individuals, although HIV infection broadens the differential diagnosis and anti-retroviral treatment complicates management. Tuberculosis in HIV infected patients should be managed either within specialist units by physicians with expertise in both HIV and tuberculosis, or in a combined approach between HIV and tuberculosis experts. The co-administration of anti-retroviral and anti-tuberculosis drugs should follow guidance issued by the British HIV association (www.bhiva.org).

Managing HIV in the PICU — The experience at the red cross War Memorial Children’s Hospital in Cape Town

The HIV pandemic has affected children throughout the developing world. This article describes the experience of the Paediatric Intensive Care Unit at the Red Cross War Memorial Children's Hospital in Cape Town, South Africa. Over the last 20 years we have improved our management of HIV infected children requiring intensive care admission. In the absence of anti-retroviral therapy, long term outcomes from PICU admission of HIV infected children have not improved significantly, and it is debatable whether PICU admission is justified. Once anti-retroviral therapy is available to children, there may be significant improvements in outcome and possible affected children should be admitted to the PICU if resources are available.

Presentation, diagnosis and management of tuberculosis in HIV-infected children in the UK

Management of HIV-infected children with tuberculosis (TB) is challenging. The objective of this study was to assess current treatment and outcomes in a resource-rich setting in the era of highly active antiretroviral therapy (HAART). A retrospective case-note review of coinfected children was carried out in a large UK-based HIV family clinic. Of 328 HIV-infected children, 18 were diagnosed and treated for active TB. TB presentation led to HIV diagnosis in eight of these 18 children. TB was confirmed microbiologically in 33% of children. Fifteen of the 18 children presented with pulmonary TB, and three with extrapulmonary TB (EPTB). Immunological status at TB diagnosis did not predict EPTB. The mean CD4 T-cell count at TB presentation was 402 cells/microL (mean CD4 percentage 16%), with a range of 0-790 cells/microL (0-34%). In seven children concurrently treated with HAART and anti-tuberculous therapy (ATT), therapeutic drug monitoring (TDM) guided management. No immune reconstitution disease occurred. There was one death, unrelated to TB, 2 years after completion of ATT. An HIV test should be considered in all children diagnosed with TB, especially if there are epidemiological risk factors. Our experience shows that, even with deferral of HAART in concurrently infected children, good therapeutic responses to ATT can be achieved. Where necessary, TDM guiding concurrent HAART and ATT can facilitate good clinical and virological responses.

Seroprevalence of hepatitis B and C viral co-infections among children infected with human immunodeficiency virus attending the paediatric HIV care and treatment center at Muhimbili National Hospital in Dar-es-Salaam, Tanzania

BackgroundWith increased availability of antibiotics and antifungal agents hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are becoming a cause for significant concern in HIV infected children. We determined the seroprevalence and risk factors for HBV and HCV among HIV infected children aged 18 months to 17 years, attending the Paediatric HIV Care and Treatment Center (CTC) at Muhimbili National Hospital (MNH) in Dar-es-Salaam, Tanzania.MethodsInvestigations included; interviews, physical examination and serology for HBsAg, IgG antibodies to HCV and alanine aminotransferase (ALT) levels. HIV serostatus and CD4 counts were obtained from patient records.Results167 HIV infected children, 88(52.7%) males and 79(47.3%) females were enrolled. The overall prevalence of hepatitis co-infection was 15%, with the seroprevalence of HBV and HCV being 1.2% and 13.8%, respectively. Hepatitis virus co-infection was not associated with any of the investigated risk factors and there was no association between HBV and HCV. Elevated ALT was associated with hepatitis viral co-infection but not with ART usage or immune status.ConclusionThe high seroprevalence (15%) of hepatitis co-infection in HIV infected children attending the Paediatrics HIV CTC at the MNH calls for routine screening of hepatitis viral co-infection and modification in the management of HIV infected children.

Recommendations in pediatric antiretroviral therapy

The pathogenesis of HIV infection and the general principles of therapy are the same for HIV-infected adults, adolescents, children and infants. However, antiretroviral treatment of HIV infection in pediatrics requires the consideration of a number of factors specific to its population, including differences in drug pharmacokinetics and the use of virologic and immunologic markers, as well as age-related adherence issues. This review summarizes the text of the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, which was updated in October 2006. The guidelines are the work of the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, a group of the Office of AIDS Research Advisory Council of the National Institutes of Health, which reviews new data on an ongoing basis and provides regular updates to the guidelines. As these guidelines were developed for the US, they may not be applicable in other countries. This summary does not attempt to place the Working Group guidelines in the context of international guidelines, nor does it attempt to detail the use of antiretroviral medication in the prevention of perinatal transmission of HIV, such as addressing the use of zidovudine versus single-dose nevirapine.

Actualités thérapeutiques dans l'infection à Virus de l'immunodéficience humaine (VIH) de l'enfant

More than 2 millions of children worldwide are HIV-infected. Recently, the HIV related mortality and morbidity has dramatically decreased due to the use of antiretroviral multitherapies in the HIV-infected children. However the therapeutic management of HIV-infected children is complex and may be complicated by socio-familial issues. Short and long term toxicity of antiretrovirals but also of HIV itself are of concern. Despite the good clinical and immunological results of antiretroviral multitherapies, virological failure may occur. Paediatric pharmacokinetic specificities and inadequate galenic presentation of drugs could lead to virological failure. However, the use of more potent drugs with more adapted presentation actually reduces this risk of failure. Prospective cohorts of HIV-infected children and new antiretroviral drugs paediatric evaluation are of key importance and can improve the paediatric therapeutic management. Finally, universal access to antiretroviral drugs in children, particularly in developing countries is the major actual and future challenge.

Progress and challenges in antiretroviral therapy for HIV-infected children

The treatment and prognosis of pediatric HIV infection in the developed world has been transformed with the introduction of highly active antiretroviral therapy. Perinatally infected children are now living into adulthood, changing the face of this epidemic from one of pessimism to one of hope. However, this transformation has brought with it many unforeseen challenges. In this review, we attempt to highlight key issues in the management of HIV-infected children, such as adherence, treatment strategies, drug resistance, and toxicities. We trust that the experience that we have accumulated can be successfully implemented in countries where treatment is urgently needed.

Growth Hormone in T-Lymphocyte Thymic and Postthymic Development: A Study in HIV-Infected Children

Vigano A, Saresella M, Trabattoni D, et al. J Pediatr. 2004;145:542–548Growth hormone (GH) plays a role in thymic function, and decreased hormone secretion has been reported in HIV-infected children. Highly active antiretroviral therapy suppresses HIV replication and results in increases in CD4+ T cells in HIV-infected patients. The aim of this study was to determine if the level of immune reconstitution associated with antiretroviral therapy is influenced by the status of the GH insulin-like growth factor 1 axis.HIV-infected children (n = 26) were studied. Half of them had GH deficiency as defined by a reduced peak GH response to GH-releasing hormone and arginine-stimulation test. These patients were matched to 13 patients of similar age, pubertal status, and clinical findings but with normal GH-response tests.Thymic volume was measured with magnetic resonance imaging. Peripheral blood lymphocyte subsets were evaluated with standard monoclonal antibody techniques. Serum interleukin 7 levels were measured with an enzyme-linked immunosorbent assay.The 2 patient populations did not differ in age, weight, height, body mass index, pubertal status, clinical or immunologic stage of disease, or number and percentage of CD4+ T cells before beginning antiretroviral therapy. After antiretroviral therapy, children with GH deficiency had reduced CD4+ T-cell numbers and percentages, reduced interleukin 7 concentrations, and reduced thymic volumes. “Naive” CD4+ T cells were lower in the GH-deficient children, as were central memory T cells. In contrast, effector memory CD4+ T cells and effector CD8+ T cells were increased in the GH-deficient children.Thymic and postthymic lymphocyte pathways are impaired in HIV-infected children, and antiretroviral therapy–associated immune reconstitution is often incomplete. GH might be useful in the management of HIV-infected children with GH deficiency and incomplete immune reconstitution with antiretroviral therapy.The reasons why some patients respond to antiretroviral therapy more effectively than others is generally unknown. However, this study suggests that some of this variation may be related to the GH axis of the infected patients. Whether GH-replacement therapy will improve the immune reconstitution in GH-deficient subjects awaits clinical trials. Of interest, also, would be the effect of GH treatment on subjects with incomplete immune reconstitution but normal GH-stimulation studies.

Advances in the prevention and treatment of paediatric HIV infection in the United Kingdom.

A summary of recent developments In the five years since our last review there have been considerable advances, both in the prevention of mother to child transmission (MTCT) of HIV, and in the treatment of HIV infected children with highly active antiretroviral therapy (HAART).1 There are now over 600 children living with HIV in the UK, the majority of whom were born to mothers who acquired HIV in Africa.2 Currently, about two thirds live in London, but this may change if refugees continue to be dispersed to other parts of the country. Antenatal testing for HIV has been shown to be cost effective throughout the UK.3 However, although uptake of testing has increased in London, rates of detection of previously undiagnosed women during pregnancy are about 60% outside London.2 HIV infected babies are still presenting seriously ill and dying with Pneumocystis carinii pneumonia (PCP) in the first months of life.4 In 1999 the Department of Health (DoH) set targets that by the end of 2002, all UK health authorities should increase uptake of antenatal HIV testing to 90%, with the aim that 80% of HIV infected pregnant women nationally would be identified and offered treatment.5 These targets will only be met if testing rates are increased outside London.6 Paediatricians throughout the UK need to be familiar with how MTCT of HIV is prevented, and how to manage children born to HIV infected mothers. This paper summarises the recent developments in prevention and management of HIV infected children. The rate of MTCT prior to the advent of interventions in Europe and USA was around 15–20%, compared with about 30% in Africa. Most of this difference is a result of breast feeding, which approximately doubles the transmission rate. In non-breast feeding populations, around two thirds …

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, January 7, 2000

These guidelines were developed by the Working Group on Antiretroviral Therapy and Medical Management of HIV Infected Children convened by the National Pediatric and Family HIV Resource Center (NPHRC), the Health Resources and Services Administration (HRSA), and the National Institutes of Health (NIH). The Co-Chairs of the Working Group were James Oleske, MD, MPH, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey, and Gwendolyn B. Scott, MD, University of Miami School of Medicine, Miami, Florida.