Pediatric HIV Patients Research Articles

Treatment Response in Association with Adherence Patterns to Highly Active Antiretroviral Therapy in Pediatric Patients with Perinatally Acquired HIV Infection

Assessment of longitudinal adherence patterns on virologic and immunologic responses to HAART in perinatally acquired HIV patients has not been studied. Perinatally infected pediatric HIV patients with adherence documented at least twice and corresponding viral load and T-cell (%) data measured during 2008-2009 were studied. Multiple adherence measures were utilized to identify patients with persistent adherence, nonadherence, or alteration of adherence. Virologic and immunologic outcomes were assessed. Persistent adherence, nonadherence, and alteration of adherence to HAART were recorded in 41.9%, 8.1%, and 50.0% of 62 studied patients. Persistent adherence was associated with higher likelihood for persistent virologic suppression and lower risk for persistent virologic failure. Alteration of adherence to HAART is a significant predictor of persistent virologic failure and high viremia in perinatally infected HIV patients. Implementation of longitudinal adherence assessments may target patients with nonsustained adherence patterns and help decrease the risk for virologic failure and disease progression.

Prevalence of Oral and Systemic Manifestations in Pediatric HIV Cohorts with and without Drug Therapy

The prevalence of orofacial and systemic manifestations and their association with drug therapy in pediatric HIV patients is scarce in the literature. The aim of the study was to determine the prevalence of oro-facial and systemic manifestations in HIV sero-positive children with and without highly active antiretroviral therapy (HAART). The study population consisted of 100 pediatric HIV patients (n=47 on HAART and n=53 not on HAART). The majority of the children (n=56) had at least one or more oro-facial manifestation associated with HIV. Oral candidiasis was the most common oral finding present in the HAART (14/33) and non-HAART groups (19/33). Recurrent aphthous ulcers was the only significant oral finding, present more in the HAART group. The percentage of children with upper respiratory tract infection was also more in the HAART group. The other lesions which were found to be significant were seborrheic dermatitis, pulmonary tuberculosis and otitis media. There was no significant difference in the participants' oral findings based on CD4 counts in the HAART and non- HAART groups. The prevalence of oral and systemic manifestations is a persistent feature associated with pediatric HIV, though of moderate intensity in those using HAART and may vary according to individual immune status.

Does a significant reduction in malaria risk make lopinavir/ritonavir-based ART cost-effective for children with HIV in co-endemic, low-resource settings?

HIV infection and malaria co-infection is not uncommon among children in co-endemic regions, and evidence suggests that HIV is a risk factor for severe malaria among children. HIV protease inhibitors (PIs) are highly effective in pediatric HIV treatment regimens, however, their effectiveness against malaria has been mixed, with some PIs demonstrating in vitro activity against Plasmodium falciparum. Recent findings suggest lopinavir/ritonavir (LPV/r)-based treatment regimens reduce the incidence of malaria infection by over 40% in pediatric HIV patients compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We assessed whether a significant reduction in malaria risk makes LPV/r-based ART regimens cost-effective compared to NNRTI-based regimens in co-endemic, low-resource settings. We modeled the difference in unit cost per disability adjusted life year (DALY) gained among two theoretical groups of HIV+ children under 5 years old receiving ART in a resource-limited setting co-endemic for malaria. The first group received standard NNRTI-based antiretrovirals, the second group received a standard regimen containing LPV/r. We used recent cohort data for the incidence reduction for malaria. Drug costs were taken from the 2011 Clinton Health Access Initiative Antiretroviral (ARV) ceiling price list. DALYs for HIV and malaria were derived from WHO estimates. Our model suggests a unit cost of US$147 per DALY gained for the LPV/r-based group compared to US$37 per DALY gained for the NNRTI-based group. In HIV and malaria co-endemic settings, considerations of PI cost effectiveness incorporating known reductions in malaria mortality suggest a nominal increase in DALYs gained for PIs over NNRTI-based regimens for HIV positive children under five on ART. Our analysis was based on several assumptions due to lack of sound data on malaria and HIV DALY attribution among pediatric populations. Further study in this area is required.

Hepatitis E virus infections in HIV-infected patients in Ghana and Cameroon

BackgroundChronic hepatitis E virus (HEV) infections have recently been described in HIV-infected patients. Only few data are available for sub-Saharan Africa, where HIV and HEV are highly co-endemic, and where liver pathology is common in HIV-infected individuals. ObjectivesTo assess the prevalence of HEV viremia, anti-HEV antibodies, and serum aminotransferase levels in HIV patients in Ghana and Cameroon. Study designWe retrospectively surveyed a cross-section of patients who were enrolled in cohort studies in Ghana (West Africa), and Cameroon (Central Africa). Plasma samples from 1029 HIV patients from Ghana and 515 patients from Cameroon including 214 children were analyzed for HEV-RNA by two reverse transcription PCR methods. In a subset of 791 patients, anti-HEV IgG and IgM antibodies were analyzed. ResultsNo HEV-RNA was detected in any of the plasma samples of 1544 patients. HEV seroprevalence was high in adult HIV patients from Ghana (45.3%, n=402) and Cameroon (14.2%, n=289), but low in pediatric HIV patients from Cameroon (2.0%, n=100). Elevations of alanine aminotransferase and aspartate aminotransferase levels were common in adult patients from Ghana (20.8% and 25.4%) and Cameroon (38.9% and 69.8%). The prevalence of hepatitis B virus surface antigen was 11.8% and of hepatitis C virus antibodies 2.5% in our adult Cameroonian study population. ConclusionsAcute or chronic HEV infections did not play a role in liver pathology in two HIV cohorts in Ghana and Cameroon. A better understanding of the epidemiology and genotype-specific characteristics of HEV infections in HIV patients in sub-Saharan Africa is needed.

CPC-058 Factors Associated with Antiretroviral Medicines Adherence Among HIV-Infected Children

BackgroundThe aims of highly active antiretroviral therapy (HAART) in HIV-infected children are to achieve and sustain full HIV-RNA viral load (VL) suppression and CD4-reconstitution, in order to prevent the progression...

Orofacial and systemic manifestations in 212 paediatric HIV patients from Chennai, South India

Lesions in the mouth and in other tissues and organs (oral and systemic lesions) in paediatric HIV infection are diverse and show differences in clinical presentation and severity from that of adults. Very little data exist for oral lesions in paediatric population in India. To document and study oral and more widespread lesions in paediatric HIV seropositive patients. A cross-sectional study. Paediatric HIV seropositive patients at tertiary centers: Ragas Dental College and Hospital and YRG CARE, Chennai, India. Two hundred and twelve paediatric HIV patients aged 0-14 years seen over a period of 1 year were included in the study. Clinical history, oral and systemic examinations were recorded by qualified dental surgeons and physicians. One hundred and thirty-two patients had oral lesions ranging in number from one to three. Oral lesions included oral candidiasis (OC) (56.1%), gingivitis (10.8%), oral pigmentation (6.1%), depapillation of the tongue (5.7%), ulcers (4.2%), and oral hairy leukoplakia (1.4%). The most common systemic lesion observed was nonspecific lymphadenopathy (74.1%) followed by pruritic eruptions (53.8%), measles (51.4%), and tuberculosis (TB) (49.1%). Thirty-three (26%) patients were not immunosuppressed, 74 (58%) were moderately immunosuppressed, and 20 (15%) were severely immunosuppressed. Oral lesions exhibited positive correlation with lesions in other parts of the body. Oral lesions are a common feature in paediatric HIV infection. Their management is vital to improve the quality of life of the infected children.

Impact of Antiretroviral Therapy on Growth, Body Composition and Metabolism in Pediatric HIV Patients

Highly active antiretroviral therapy improves survival and growth in children with HIV infection. However, its use can be associated with adverse changes in body composition and metabolism. Bone mineral density can be adversely affected in HIV-positive children due to nutritional compromise or certain antiretrovirals. HIV-associated lipodystrophy, consisting of redistribution of adipose tissue, insulin resistance, and dyslipidemia, has also been described in children. Pediatric HIV patients may be at greater risk for these problems because of their longer potential lifetime exposure to these agents and because childhood is normally a period of rapid growth and tissue accretion. Healthcare providers for children with HIV infection must be aware of the potential complications associated with HIV antiretrovirals so that their antiviral efficacy can be balanced against their risk for side effects. In this review, we discuss the alterations in childhood growth and body composition that occur in HIV-infected children, and describe the impact of antiretroviral therapy on these outcomes. The problem of HIV-associated lipodystrophy syndrome in children is also discussed. Children with HIV should have their growth and body composition systematically monitored. Antiretroviral regimens should be tailored to optimize adherence and viral suppression while minimizing the potential for adverse side effects.

The link between religion and HAART adherence in pediatric HIV patients

HIV is a chronic illness that requires strict adherence to medication regimens. This study attempts to examine the patterns of highly active antiretroviral therapy adherence relative to religious beliefs in a population of perinatally HIV-infected adolescents. Eligible subjects included perinatally HIV-infected youth aged 14–22 years who knew their HIV status. Assessment tools included an antiretroviral adherence form, a standardized depression questionnaire, and a religious observance questionnaire. All of these forms were completed at the time of study enrollment. Twenty subjects met entry criteria and were enrolled. Subjects who had excellent adherence had significantly higher religious belief scores than those who had poor adherence (3.46±0.46 vs. 2.34±0.69, p<0.05). Those with excellent adherence also had higher religious practice scores than those with poor adherence (2.66±1.02 vs. 2.23±1.45, p=0.46). Beck Depression Inventory (BDI)-II depression score was also lower in those with excellent adherence versus those with poor adherence (4.64±3.41 vs. 8.86±9.77, p=0.39). Physicians may be able to consider spirituality as a factor that may influence medication adherence in pediatric HIV patients. As perinatally HIV-infected youth age into adulthood, future studies will be needed to explore the ongoing intimate relationship between a patient's religious views and their compliance to medical regimens.

A Highly Concentrated and Taste-Improved Aqueous Formulation of Efavirenz for a More Appropriate Pediatric Management of the Anti-HIV Therapy

Pediatric HIV is scarce in developed countries; 90% of pediatric HIV patients are in developing countries. In contrast, children represent 15% of the new infections in poor countries. Approximately 90% of the HIV-positive children do not have access to antiretrovirals (ARVs). Without treatment, 50% of the patients die before the 2 years of age. Efavirenz (EFV, aqueous solubility approximately 4 microg/mL, 40-45% bioavailability), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is a first-choice pediatric ARV. To assure therapeutic plasma concentrations, the low oral bioavailability demands the administration of relatively high EFV doses. Aqueous EFV irritates the oral mucosa, causing a Burning Mouth Syndrome (BMS). A triglyceride-based liquid formulation of EFV (30 mg/mL) is not commercially available worldwide, making the appropriate dose adjustment and the swallowing difficult. More importantly, clinical trials indicated that the oral bioavailability of this oily solution is lower than that of the solid one. Moreover, a relatively high inter-subject variability has been found. The present work reports the development and full characterization of a concentrated (20 mg/mL, 2%) and taste-masked aqueous formulation of EFV for a more appropriate management of the pediatric anti-HIV therapy. Formulations displayed high physicochemical stability over time under regular storage conditions. Release assays in vitro showed a burst effect (2 h) and zero-order kinetics later on (between 2 and 24 h), compatible with the oral administration route and release. Finally, taste tests performed by adult healthy volunteers indicated that the unique combination of flavors and sweeteners employed (i) reduced the intensity of the BMS and (ii) shortened its duration significantly. Overall results indicate that the cost-effective and scalable nanotechnological strategy proposed could enable the more convenient and compliant administration of lower EFV doses. Due to a better pharmacokinetic profile, this would result in similar plasma levels than higher doses administered in solid or triglyceride-soluble form. In this context, some reduction of the treatment cost can be envisioned. This could improve the access of less affluent pediatric patients to medication in poor countries.

PROTEASE INHIBITOR RESISTANCE IN SOUTH AFRICAN CHILDREN WITH VIROLOGIC FAILURE

In South Africa, first-line antiretroviral therapy for children younger than 3 years of age combines a protease inhibitor (PI) with 2 nucleoside reverse transcription inhibitors. In our study, some pediatric patients received ritonavir (RTV) as single PI (RTV-sPI) and others ritonavir-boosted lopinavir (LPV/r), which has a higher resistance barrier. We explored antiretroviral resistance mutations in pediatric patients failing PI-based antiretroviral therapy and the predictors of major PI resistance mutations (MPIRM) in these patients. We studied pediatric HIV patients at Tygerberg Academic Hospital experiencing virologic failure on a PI regimen. Mixed-effects linear- and mixed-effect logistic regression modeling, were used to explore predictors of MPIRM. MPIRM were found in 12 of 17 patients exposed to RTV-sPI compared with 1 of 13 patients treated with LPV/r. Exposure to RTV-sPI was significantly associated with MPIRM, with both exposure time and estimated failing time on RTV-sPI being significant positive predictors of MPIRM. Neither CD4 count, viral load, age at first visit nor receiving rifampin predicted MPIRM. RTV-sPI in infants and children poses a significant risk of MPIRM which is dependent on the exposure time and time failing while receiving the regimen.

POLYSOMNOGRAM FINDINGS OF OBSTRUCTIVE SLEEP APNEA FOR CHILDREN WITH HIV

PURPOSE: There is a paucity of literature in the PubMed Database regarding sleep characteristics and polysomnographic findings regarding pediatric HIV patients. The objective of this abstract is to provide some preliminary data regarding the prevalence of obstructive sleep apnea in this patient population.

Managing treatment-experienced pediatric and adolescent HIV patients: role of darunavir

Darunavir is currently the most recently approved HIV-1 protease inhibitor. It is approved for twice-daily dosing with ritonavir in treatment-experienced patients as young as 6 years of age and is available in numerous pill strengths. Emergence of darunavir-specific mutations is generally slow; therefore it can retain activity against viral strains that are resistant to other protease inhibitors, including tipranavir. Darunavir pharmacokinetics, clinical efficacy, resistance mutations and pharmacodynamics, and adverse effects are reviewed here. Substantial data support its use as a potent, well-tolerated option for salvage therapy in highly treatment-experienced children and adolescents.

Implementation of a comprehensive program including psycho-social and treatment literacy activities to improve adherence to HIV care and treatment for a pediatric population in Kenya

BackgroundTo achieve good clinical outcomes with HAART, patient adherence to treatment and care is a key factor. Since the literature on how to care for pediatric HIV patients is limited, we describe here adherence interventions implemented in our comprehensive care program in a resource-limited setting in Kenya.MethodsWe based our program on factors reported to influence adherence to HIV care and treatment. We describe, in detail, our program with respect to how we adapted our clinical settings, implemented psycho-social support activities for children and their caregivers and developed treatment literacy for children and teenagers living with HIV/AIDS.ResultsThis paper focused on the details of the program, with the treatment outcomes as secondary. However, our program appeared to have been effective; for 648 children under 15 years of age who were started on HAART, the Kaplan-Meier mortality survival estimate was 95.27% (95%CI 93.16–96.74) at 12 months after the time of initiation of HAART.ConclusionOur model of pediatric HIV/AIDS care, focused on a child-centered approach with inclusion of caregivers and extended family, addressed the main factors influencing treatment adherence. It appeared to produce good results and is replicable in resource-limited settings.

Development of fixed dose combination tablets containing zidovudine and lamivudine for paediatric applications

In view of the lack of suitable paediatric antiretroviral formulations on the market, a novel fixed dose combination (FDC) tablet containing 300 mg zidovudine (AZT) and 160 mg lamivudine (3TC) was developed to improve dosing accuracy and allow flexible drug dosing in function of the body weight of paediatric HIV patients as recommended by WHO. Rectangular tablets with multiple fraction bars were designed and each tablet can be broken into 8 subunits, each subunit containing a drug dose corresponding to a body weight of 5 kg. These fast-disintegrating subunits can easily be administered to children after dispersion in a liquid or mixing with food. In vitro quality control of the FDC tablets was determined and a crossover bioavailability study using 18 adult volunteers was performed after oral administration of the novel FDC tablet and a Duovir tablet. The results of the study showed that the novel tablets as well as its subunits disintegrated fast (<20 s). After 30 min dissolution, AZT and 3TC released from Duovir ® and the novel tablets was above 95%, the similarity factors f2 were above 50 for both AZT and 3TC. A tablet breakability test showed low weight variability (125.1 ± 5 mg, R.S.D. = 4.4%), with limited weight loss (0.3%). There was no significant difference in pharmacokinetic parameters ( C max, t max and AUC 0–12 h values) between Duovir and the novel tablets formulated for paediatric applications.

Viral loads in pediatric HIV patients with antiretroviral treatment

Viral load in pediatric patients with HIV infections can help to make therapeutic decisions to modify the evolution of the disease. To evaluate viral load in positive HIV children with antiretroviral treatment. Viral load was measured every six months during three years in fifty pediatric patients chosen randomly in aged 1 to 12 years, using the Test Monitor HIV-1 AMPLICOR, version 1.5. During the three years follow up, there was an increase in CD4 and CD8 lymphocyte count and decrease in the viral load. However, there was no significant relationship between lymphocyte subpopulation counts and viral loads. Viral load demonstrated to be an appropriate method to quantify plasma HIV-RNA. This tool can help to define the condition of a particular patient to predict clinical course of the disease and to assess the response to the treatment.

Solid Organ Transplantation and HIV: A Changing Paradigm

Solid Organ Transplantation and HIV: A Changing Paradigm

The frequency of oral findings in pediatric HIV patients

Objective. The purpose of this ongoing observational study is to evaluate the frequency of abnormal oral findings in HIV-infected children. In addition, the relationship between immune status and oral findings will be explored.

Immunological Analysis in Paediatric HIV Patients at Different Stages of the Disease

There are only few clinical studies on complement in well-defined (or characterized) paediatric HIV patients. Aim of this study was to evaluate the complement system and immunoglobulins in HIV-infected children and to correlate data to stage of disease. Blood samples of 127 HIV-infected children (11-134 months; 62 male : 65 female) were collected in order to evaluate humoral immunity. The patients were classified according to CDC clinical (N-asymptomatic; A-mild symptoms such as common recurrent infections; B-moderate symptoms such as Candidiasis and herpes infections, meningitis, sepsis and anaemia; C-severe symptoms such as opportunistic infections and neoplasia) and with respect to immunological criteria (T CD4(+) cell count). Analysis of complement system included the classical (CH50), alternative (APH50) pathway activities and plasma concentrations of mannan-binding lectin (MBL), of the C4 allotypic variants C4A and C4B. (ELISA), and of the C3 split product C3d (rocket immunoeletrophoresis). Immunodiagnosis also included CD4(+) and CD8(+) lymphocyte count and immunoglobulin concentrations. Complement activation and consumption was observed in all patients correlating with disease activity. Activated classical and alternative pathways and elevated C3d were significantly correlated with immunologic category 3. C3d levels were also significantly correlated with immunologic category 1. Undetectable CH50 and APH50 were found in two (group C) and 10 patients (n = 2, A = 2, B = 2, C = 4), respectively. Low MBL values were found in 13/127 but without correlation to disease severity. Undetectable C4B levels were observed in three patients, favouring the diagnosis of a complete deficiency. Although not related to clinical symptomatology, a strong ongoing complement activation can be observed in all stages of HIV infection. In contrast to earlier reports MBL could not be considered as a risk factor for HIV.

Evaluation of Short Course Direct Observational Therapy in Pediatric Hiv Patients

Evaluation of Short Course Direct Observational Therapy in Pediatric Hiv Patients

Nutrition Management Guidelines for Pediatric HIV+ Patients

Six regions of the United States developed multidisciplinary pediatric HIV-specialist working groups to address nutrition issues in pediatric HIV disease. Literature reviews and professional experiences were summarized and translated into nutrition assessment and management guidelines. The groups included physicians, nurses, nurse practitioners, dietitians, and social workers from Chicago, Los Angeles, Miami/Tampa, New York/New Jersey, San Francisco/Oakland, and Washington DC. Members of the groups agreed that cases of newborn transmission have been dramatically reduced while cases of long-term survivors infected prior to perinatal use of anti-HIV drugs, children of undiagnosed mothers, and sexually infected children and adolescents may be rising. Nutritional issues of failure-to-thrive still exist, especially in antiretroviral naive children. Cultural issues, family dynamics, inadequate housing, and health care access play a large role in the support of health and survival in the pediatric HIV patient and are often the higher priority above nutrition assessment and management. However, nutrition issues are considered an equal priority with other medical issues. The Centers for Disease Control definition of wasting in pediatric HIV disease was considered inadequate and alternate definitions for the identification of nutritional compromise varied from region to region. Nutrition-related interventions were primarily food-based with supplements as needed. Adjunctive therapies included appetite stimulants and anabolic therapies, though few were commonly used. Particular concern was expressed for culturally appropriate educational materials and methods. Multidisciplinary approaches were encouraged. Guidelines based on the input from the six groups and other reviewers were developed for field testing in the San Francisco/Oakland area and will be available for field-testing and as a basis for nutrition program development for pediatric HIV patients elsewhere in the United States.