HIV-infected Pediatric Patients Research Articles

Steady-State Pharmacokinetics of Tenofovir-Based Regimens in HIV-Infected Pediatric Patients

HIV-infected children are treated with tenofovir in combination with other, potentially interacting, antiretroviral agents. We report the pharmacokinetic parameters of tenofovir in combination with efavirenz, darunavir-ritonavir, or atazanavir-ritonavir in HIV-infected children. HIV-infected patients 8 to 18 years of age receiving a tenofovir (300 mg)-based regimen containing efavirenz (300 or 600 mg) once daily (group 1), darunavir (300 or 600 mg)-ritonavir (100 mg) twice daily (group 2), or atazanavir (150 to 400 mg)-ritonavir (100 mg) once daily (group 3) were enrolled. Plasma samples were collected over a 24-h time interval. The 90% confidence intervals (90% CI) of the geometric means for the area under the plasma concentration-time curve (AUC) and the minimum concentration of drug in serum (C(min)) of each antiretroviral were computed and checked for overlap with intervals bracketing published values obtained in adult or pediatric studies demonstrating safety and/or efficacy. Group 1 efavirenz plasma concentrations were observed to be higher in patients receiving fixed-dose combination tablets compared with subjects receiving the individual formulation. In group 2, tenofovir and darunavir exposure was observed to be lower than expected. In group 3, tenofovir and atazanavir administered concomitantly produced exposures similar to those published for adult patients. The 90% CI of AUC and C(min) for tenofovir overlapped the target range for all combinations. Informal comparisons of treatment groups did not indicate any advantage to any combination with respect to tenofovir exposure. Further study of exposures achieved with antiretrovirals administered in combination is warranted.

Antiretroviral Drugs in Pediatric HIV-Infected Patients

Antiretroviral (ARV) therapy has been shown to achieve high therapeutic efficacy in treating pediatric HIV disease. The delivery of affordable, child friendly, and easy to store and administer ARV drugs is key to the successful management of HIV in children. In recent years, significant progress has been made in scaling up the access to pediatric ARV therapy among children worldwide. Despite the improved ARV drug access, multiple challenges remain concerning palatability and efficient delivery of ARV drugs to children from infancy into adolescence. Data are limited regarding developmental changes in pharmacokinetics of individual ARV drugs, and pediatric and adult fixed-dose combinations. This review provides a practical discussion regarding the pharmacokinetics of ARV agents in pediatric HIV-infected patients, as well as the practical challenges of currently available formulations, such as palatability of liquid formulations, challenges of crushing tablets, and using adult and pediatric fixed-dose combinations.

Causes of Death in Pediatric Patients Vertically Infected by the Human Immunodeficiency Virus Type 1 in Madrid, Spain, From 1982 to Mid-2009

Effective therapies have increased life expectancy of human immunodeficiency virus (HIV)-infected pediatric patients. We investigated the underlying causes of death, mortality, and acquired immune deficiency syndrome (AIDS) rates in HIV-infected pediatric patients in Madrid, Spain. We studied a multicenter cohort of 478 HIV-infected pediatric patients in Madrid. Mortality and AIDS incidence rates, causes of death, CD4 T-cell, and HIV RNA were analyzed during calendar periods (CPs): pre-HAART (highly active antiretroviral therapy) (CP1: 1982-1996) and post-HAART era (CP2: 1997-2009). During 5690 person-years of follow-up 157 (32.8%) deaths occurred. Median age at death increased (CP1: 3.2 years [1.0-6.3] vs. CP2: 7.7 years [3.1-11.4]; P < 0.01). Mortality and AIDS rates decreased 10.6-fold (95% confidence intervals [CI]: 6.9-16.7) and 6.9-fold (95% CI: 5.0-9.6), respectively, between CPs. Nevertheless, mortality was 10.4-fold (95% CI: 5.8-18.8; P < 0.001) higher than in age-similar general population in late-CP2. In all, 169 causes of death were reported. Multiple causes were reported in 16 of 151 (10.6%) patients. In 81.1% (137/169), the causes were AIDS-defining, 11.8% (20/169) HIV-related, and 7.1% (12/169) non-HIV-related. Infections were the leading causes (60.8%, 101/166); from 1999 to 2007 the risk of death from infections was 115.9 times (95% CI: 42.0-265.8; P < 0.001) higher than in the age-similar general population. Comorbidity was reported in 66.9% (101/151) of patients. Median HIV-1 RNA at death decreased (CP1: 5.9 [5.0-6.3]; CP2: 5.3 [4.2-5.8]; P < 0.01). Despite decline in mortality and AIDS rates, it is important to monitor all causes of death as prolonged survival might allow underlying comorbidity to become more clinically relevant.

Epstein-Barr virus-associated leiomyosarcoma with cutaneous involvement in an African child with human immunodeficiency virus: a case report and review of the literature

Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) are infrequently encountered lesions restricted to immunocompromised patients. However, they represent the second most common tumor in children with human immunodeficiency virus (HIV) infection. We report a case of a progressively enlarging abdominal mass with cutaneous involvement in an HIV-infected, 4-year-old African girl in Malawi with clinical acquired immunodeficiency syndrome on highly active antiretroviral therapy. Analysis of an excisional specimen revealed a well-differentiated leiomyosarcoma and subsequent studies revealed diffuse nuclear positivity for Epstein-Barr virus early RNAs in lesional cells. We present a report of this case and provide a summary of the literature regarding SMTs in pediatric HIV-infected patients. In addition, we draw attention to the cutaneous manifestations of SMTs in immunosuppressed populations. We highlight EBV-related SMTs as a potential cutaneous complication of HIV infection in children and immunosuppressed patients populations as a whole.

PANDEMIC INFLUENZA A (2009 H1N1) IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CATALAN CHILDREN

No data are available on 2009 H1N1 influenza in human immunodeficiency virus (HIV)-infected children, a highly susceptible and vulnerable population. We report 13 cases of pandemic influenza among a cohort of HIV-infected pediatric patients. Clinical features of H1N1 influenza were similar to those described in the general population. Most patients received antivirals on an outpatient basis. An uneventful evolution was observed in all patients, only 2 of whom required hospitalization. Influenza had no effect on the evolution of HIV infection.

Prospective study of renal function in HIV-infected pediatric patients receiving tenofovir-containing HAART regimens

to describe the impact of tenofovir disoproxil fumarate (TDF) use on renal function in HIV-infected pediatric patients. it is a prospective, multicenter study. The setting consisted of five third-level pediatric hospitals in Spain. The study was conducted on patients aged 18 years and younger who had received TDF for at least 6 months. The intervention was based on the study of renal function parameters by urine and serum analyses. The main outcome measures were renal function results following at least 6 months of TDF therapy. forty patients were included (32 were white and 26 were diagnosed with AIDS). Median (range) duration of TDF treatment was 77 months (16-143). There were no significant changes in the estimated creatinine clearance. Urine osmolality was abnormal in eight of 37 patients, a decrease in tubular phosphate absorption was documented in 28 of 38 patients, and 33 of 37 patients had proteinuria. A statistically significant decrease in serum phosphate and potassium concentrations was observed during treatment (P = 0.005 and P = 0.003, respectively), as well as a significant relationship between final phosphate concentration and tubular phosphate absorption (P = 0.010). A negative correlation was found between phosphate concentration and time on TDF. TDF use showed a significant association with renal tubular dysfunction in HIV-infected pediatric patients. Periodic assessment of tubular function may be advisable in the follow-up of this population.

Evolution of Mitochondrial DNA Content After Planned Interruption of HAART in HIV-Infected Pediatric Patients

HAART-related long-term toxicities, many of them ascribed to mitochondrial (mt) toxicity of the nucleoside analogues, are being increasingly reported in HIV-infected children. HIV infection can also cause mt damage. Case series include 13 vertically HIV-infected pediatric patients (9 girls, median age 10.5 years) with optimal long-term response to a first-line HAART regimen who underwent planned treatment interruption (PTI). MtDNA content from peripheral blood mononuclear cells was assessed by means of a real-time PCR technique at PTI and 12 months later and expressed as an mtDNA/nuclear DNA ratio, together with lactate levels. At PTI, patients had remained a median time of 4.7 years on HAART and 4.3 years with complete suppression of viral replication. The main reason leading to PTI was treatment fatigue. One month after PTI, HIV plasmatic viral load had increased to 4.8 log copies/ml and stabilized thereafter. During the 12-month study period, all children remained free from any HIV-related clinical event. A progressive and significant decrease in median CD4 cell counts and percentages was observed 12 months after PTI. One year after PTI, the median mtDNA/nuclear DNA ratios had increased from 0.76 to 1.08 (p = 0.002) and lactate levels had decreased (from 1.12 to 0.73 mmol/liter; p = 0.019). Changes in mtDNA did not correlate with changes in lactate levels. No relationship was found between the evolution in mt toxicity markers and the rest of the clinical, immunological, and virological variables. In this series, PTI led to a partial restoration of mtDNA levels and a significant decrease in lactate values.

Mitochondrial Assessment in Asymptomatic HIV-Infected Paediatric Patients on Haart

HAART can cause mitochondrial DNA (mtDNA) depletion, which may lead to mitochondrial dysfunction. We aimed to determine whether mtDNA and mitochondrial function abnormalities are present in peripheral blood mononuclear cells from asymptomatic HIV-infected children. A cross-sectional study in peripheral blood mononuclear cells was performed in 47 asymptomatic (free from any HIV- or AIDS-related active condition or HAART-related toxicity), HIV-infected, HAART-treated children and adolescents and 27 uninfected healthy paediatric patients. We measured mtDNA and mitochondrial RNA (mtRNA) content by quantitative real-time PCR. Mitochondrial respiratory chain enzymatic activity of complex-IV (CIV) and mitochondrial mass (estimated by citrate synthase) were measured spectrophotometrically, and CIV protein subunit content was measured with western blot analysis. A reduction in mtDNA levels was observed in HIV-infected children compared with controls (mean ± sem 4.47 ± 0.31 and 5.82 ± 0.48, respectively; 23% depletion; P=0.018), whereas similar levels of mtRNA, CIV protein subunit content and enzymatic activity were found in the two groups. These findings remained unaltered after considering mitochondrial abundance. Among HIV-infected children, mtDNA levels did not correlate with viral load, CD4(+) T-cell counts or lactataemia at the time of assessment. No differences were observed when current or past use of individual antiretroviral drugs or HAART regimens were taken into account. Depletion in mtDNA from asymptomatic HIV-infected children did not lead to differences in mtRNA levels or mitochondrially-encoded CIV proteins, nor to CIV dysfunction. This may be explained by homeostatic-compensatory mechanisms at the transcription level or by the mild depletion we observed.

A young patient with perinatal HIV infection treated for 17 consecutive years with antiretroviral therapy: extremely severe lipo-accumulation picture

Background Like adults, also pediatric HIV-infected patients (p) are prone to suffer from a lipodystrophy syndrome, usually accompanied by dysmetabolic disorders. The psychological consequences of the morphologic changes are expected to be particularly devastating in development ages. Methods Like adults, also pediatric HIV-infected patients (p) are prone to suffer from a lipodystrophy syndrome, usually accompanied by dysmetabolic disorders. The psychological consequences of the morphologic changes are expected to be particularly devastating in development ages.

Autologous Neutralizing Antibody to Human Immunodeficiency Virus-1 and Replication-Competent Virus Recovered from CD4+T-Cell Reservoirs in Pediatric HIV-1–Infected Patients on HAART

A patient's ability to produce autologous neutralizing antibody (ANAB) to current and past HIV isolates correlates with reduced disease progression and protects against maternal-fetal transmission. Little is known about the effects of prolonged viral suppression on the ANAB response in pediatric HIV-infected patients receiving HAART because the virus is hard to isolate, except by special methods. We therefore assessed ANAB to pre-HAART PBMC virus isolates and post-HAART replication-competent virus (RCV) isolates recovered from latent CD4(+) T-cell reservoirs in perinatally HIV-infected children by using a PBMC-based assay and 90% neutralization titers. We studied two infants and three children before and after HAART. At the time of RCV isolation (n = 4), plasma HIV RNA was <50 copies/ml. At baseline, four of five children had detectable ANAB titers to concurrent pre-HAART virus isolates. Although ANAB was detected in all subjects at several time points despite prolonged HAART and undetectable viremia, the response was variable. ANAB titers to concurrent post-HAART RCV and earlier pre-HAART plasma were present in 3 children suggesting prior exposure to this virus. Post-HAART RCV isolates had reduced replication kinetics in vitro compared to pre-HAART viruses. The presence of ANAB over time suggests that low levels of viral replication may still be ongoing despite HAART. The observation of baseline ANAB activity with earlier plasma against a later RCV suggests that the "latent" reservoir may be established early in life before HAART.

Metabolic complications associated with antiretroviral therapy in HIV-infected and HIV-exposed uninfected paediatric patients

Importance of the field: HIV-infection has become a chronic disease in paediatric patients with the potential for long-term survival and exposure to antiretroviral (ARV) therapies for 2 decades longer than HIV-infected adults. On the other hand, the administration of ARV to HIV-infected pregnant women has greatly increased both treatment of HIV infection and prevention of perinatal HIV transmission. Therefore, researches aiming to evaluate the safety of ARV therapies in HIV-infected children as well as in HIV-uninfected infants born to HIV-infected mothers are emerging as a new challenge and urgent priority.Areas covered in this review: The purpose of this review is to describe some of the more concerning metabolic complications associated with ARV in paediatric population: hyperlactataemia (HLA) syndromes, body shape abnormalities, disorders of glucose homeostasis and dyslipidaemia in HIV-infected children and adolescents. Frequency, risk factors, clinical findings, prevention and intervention strategies of the previously described abnormalities are discussed in depth.What the reader will gain: This review covers our current understanding of HLA syndromes in ARV-exposed uninfected infants born to HIV-infected mothers.Take home message: Prevention of these metabolic complications should assume prominence and future researches should address several of the existing treatment gaps.

Barriers and facilitators to antiretroviral medication adherence among HIV-infected paediatric patients in Ethiopia: A qualitative study

Medication adherence is a complex behaviour with multiple determinants. Understanding the barriers and facilitators of adherence is invaluable for programme improvement, which assists the foundation of adherence intervention strategies. A qualitative study was conducted in six selected hospitals of Addis Ababa in 2008, to explore barriers and facilitators to antiretroviral medication adherence among HIV-infected paediatric patients. Twelve caregivers of adherent and non-adherent children and 14 key informants in five hospitals were included in the study. The findings revealed that over-dosage (heavy pill burden), fear of stigma and discrimination, cost and access to transportation, lack of understanding of the benefit of taking the medication, economic problems in the household, and lack of nutritional support were the barriers to adherence to HAART. The presence of mobile/wall alarm, the presence of follow-up counselling, improved health of the child, ART clinic setups, and disclosure of HIV serostatus were among the facilitators. This study indicated that paediatric adherence to antiretroviral therapy faces a huge challenge. It suggests the provision of income-generating schemes to caregivers for assisting HIV-infected children. Health care providers should address proper usage of medication reminders.

No Influence of Nevirapine on Vitamin D Deficiency in HIV-Infected Patients

AIDS Research and Human RetrovirusesVol. 25, No. 8 Letter to the EditorNo Influence of Nevirapine on Vitamin D Deficiency in HIV-Infected PatientsEmanuela Lattuada, Massimiliano Lanzafame, Giacomo Zoppini, Ercole Concia, and Sandro VentoEmanuela LattuadaInfectious Diseases Unit, Policlinico G.B. Rossi B.go Roma, Verona, Italy.Search for more papers by this author, Massimiliano LanzafameInfectious Diseases Unit, Policlinico G.B. Rossi B.go Roma, Verona, Italy.Search for more papers by this author, Giacomo ZoppiniEndocrinologic Unit, Department of Biomedical and Surgical Sciences, University of Verona, Ospedale Civile Maggiore B.go Trento, Verona, Italy.Search for more papers by this author, Ercole ConciaInfectious Diseases Unit, Policlinico G.B. Rossi B.go Roma, Verona, Italy.Search for more papers by this author, and Sandro VentoInfectious Diseases Unit, Annunziata Hospital, Cosenza, Italy.Search for more papers by this authorPublished Online:13 Aug 2009https://doi.org/10.1089/aid.2009.0063AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"No Influence of Nevirapine on Vitamin D Deficiency in HIV-Infected Patients." , 25(8), pp. 849–850FiguresReferencesRelatedDetailsCited byDetermination of optimal vitamin D 3 dosing regimens in HIV-infected paediatric patients using a population pharmacokinetic approach20 October 2014 | British Journal of Clinical Pharmacology, Vol. 78, No. 5Vitamin D and Calcium Abnormalities in the HIV-Infected PopulationEndocrinology and Metabolism Clinics of North America, Vol. 43, No. 3Change in Vitamin D Levels and Risk of Severe Vitamin D Deficiency over 48 Weeks among HIV-1-Infected, Treatment-Naive Adults Receiving Rilpivirine or Efavirenz in a Phase III Trial (Echo)1 February 2013 | Antiviral Therapy, Vol. 19, No. 2Vitamin D 3 supplementation scheme in HIV-infected patients based upon pharmacokinetic modelling of 25-hydroxycholecalciferol8 April 2013 | British Journal of Clinical Pharmacology, Vol. 75, No. 5A potential influence of vitamin D on HIV infection and bone disease in HIV-positive patientsHIV & AIDS Review, Vol. 12, No. 4Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patientsAIDS, Vol. 26, No. 3Prevalence of Hypovitaminosis D and Factors Associated With Vitamin D Deficiency and Morbidity Among HIV-Infected Patients Enrolled in a Large Italian CohortJAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 58, No. 2Vitamin D in HIV-Infected Patients7 June 2011 | Current HIV/AIDS Reports, Vol. 8, No. 3Do nevirapine and efavirenz affect vitamin D homeostasis similarly?AIDS, Vol. 25, No. 6Is lower serum 25-hydroxy vitamin D associated with efavirenz or the non-nucleoside reverse transcriptase inhibitor class?AIDS, Vol. 25, No. 6Vitamin D deficiency is associated with type 2 diabetes mellitus in HIV infectionAIDS, Vol. 25, No. 4The Rapidly Evolving Research on Vitamin D Among HIV-Infected Populations23 November 2010 | Current Infectious Disease Reports, Vol. 13, No. 1Low Vitamin D among HIV-Infected Adults: Prevalence of and Risk Factors for Low Vitamin D Levels in a Cohort of HIV-Infected Adults and Comparison to Prevalence among Adults in the US General Population9 January 2011 | Clinical Infectious Diseases, Vol. 52, No. 3 Volume 25Issue 8Aug 2009 InformationCopyright 2009, Mary Ann Liebert, Inc.To cite this article:Emanuela Lattuada, Massimiliano Lanzafame, Giacomo Zoppini, Ercole Concia, and Sandro Vento.No Influence of Nevirapine on Vitamin D Deficiency in HIV-Infected Patients.AIDS Research and Human Retroviruses.Aug 2009.849-850.http://doi.org/10.1089/aid.2009.0063Published in Volume: 25 Issue 8: August 13, 2009Online Ahead of Print:July 20, 2009PDF download

Diagnosis and Management of Tuberculous Meningitis in HIV-Infected Pediatric Patients

Rowe, Jack S. BA*; Shah, Samir S. MD, MSCE*†‡§; Marais, Ben J. MD, PhD¶; Steenhoff, Andrew P. MD*†§∥ Author Information

Adherence to highly active antiretroviral therapy and its correlates among HIV infected pediatric patients in Ethiopia

BackgroundThe introduction of combination antiretroviral therapy (ART) has resulted in striking reductions in HIV-related mortality. Despite increased availability of ART, children remain a neglected population. This may be due to concerns that failure to adhere appears to be related to continued viral replication, treatment failure and the emergence of drug-resistant strains of HIV. This study determines the rates and factors associated with adherence to Antiretroviral (ARV) Drug therapy in HIV-infected children who were receiving Highly Active Antiretroviral Therapy (HAART) in Addis Ababa, Ethiopia in 2008.MethodsA cross-sectional study was conducted in five hospitals in Addis Ababa from February 18 – April 28, 2008. The study population entailed parents/caretaker and index children who were following ART in the health facilities. A structured questionnaire was used for data collection.ResultsA total of 390 children respondents were included in the study with a response rate of 91%. The majority, equaling 205 (52.6%) of the children, were greater than 9 years of age. Fifty five percent of the children were girls. A total of 339 children (86.9%) as reported by caregivers were adherent to antiretroviral drugs for the past 7 days before the interview. Numerous variables were found to be significantly associated with adherence: children whose parents did not pay a fee for treatment [OR = 0.39 (95%CI: 0.16, 0.92)], children who had ever received any nutritional support from the clinic [OR = 0.34 (95%CI: 0.14, 0.79)] were less likely to adhere. Whereas children who took co-trimoxazole medication/syrup besides ARVs [OR = 3.65 (95%CI: 1.24, 10.74)], children who did not know their sero-status [OR = 2.53 (95%CI: 1.24, 5.19)] and children who were not aware of their caregiver's health problem [OR = 2.45 (95%CI: 1.25, 4.81)] were more likely to adhere than their counterparts.ConclusionAdherence to HAART in children in Addis Ababa was higher than other similar setups. However, there are still significant numbers of children who are non-adherent to HAART.

Tipranavir: a new protease inhibitor for the pediatric population

Highly active antiretroviral therapy can provide sustained viral suppression and a beneficial immunological response in both antiretroviral-naive and -experienced pediatric patients infected with HIV. While there have been many antiretroviral studies in adults infected with HIV, considerably less information is available in similar HIV-infected pediatric or adolescent patients. Tipranavir, a new-generation protease inhibitor approved for use in adults with resistant HIV strains, has recently been studied in HIV-infected children and adolescents. In this article, we summarize available pharmacokinetic, safety, tolerability and efficacy data obtained from children and adolescents treated with a pediatric tipranavir formulation.

Long-term use of bisphosphonates in the treatment of HIV-related bone pain in perinatally infected pediatric patients

Long-term use of bisphosphonates in the treatment of HIV-related bone pain in perinatally infected pediatric patients

CD4 T cell measurements in the management of antiretroviral therapy-A review with an emphasis on pediatric HIV-infected patients

The measurement of both the percentage (in pediatric patients aged less than 5 or 6 years) and the absolute number of circulating CD4+ T cells remains the single most important parameter for establishing prognosis and determining when to treat HIV-1 infected infants. The predictive power of CD4+ T cell measurements in HIV-1 infected individuals has resulted in robust guidelines from numerous agencies on the use of CD4+ T cell measurements ranging from pretreatment evaluations to the initial assessment and monitoring of therapeutic responses and treatment failures. The increase in availability of HIV-1 antiretroviral drugs in resource limited setting has led to the urgent need to develop systems and technologies for the accurate and cost-effective measurement of CD4+ T cells. The establishment of standardized guidelines for antiretroviral therapy (including CD4 testing) along with significant advancements in the development of structured access to health care, centralized CD4 testing programs, improved quality assurance programs, and inexpensive CD4 measurement technologies are making CD4 testing more universally available. Recent evidence suggests that a CD4/CD8 ratio of less than 1 may provide a reliable marker of presumptive HIV-1 infection in HIV-1 exposed infants. This review will summarize the current guidelines for the use of CD4 testing in HIV-1 infected infants and the potential for the CD4:CD8 ratio to be used as a surrogate of HIV-1 infection in resource limited settings.

Role of common gamma chain utilizing cytokines for immune reconstitution in HIV infection

Many cytokines that utilize the common gamma (Cgamma) chain signaling pathway, viz Interleukin (IL)-2, IL-15, and IL-7 are known to be important for inducing T cell maturation, proliferation, or survival. Untreated chronic HIV infection is associated with profound quantitative and qualitative deficiency of CD4 T cells, which is partially reversed following highly active antiretroviral therapy (HAART). A subset of patients, however, fail to recover CD4 T cells despite virologic suppression. The role of Cgamma chain cytokines in influencing immune reconstitution following potent antiretroviral therapy is discussed. Maturation markers (naïve, central memory, effector memory, and effector), cytokine receptors IL-2Rbeta, Cgamma chain, IL-7Ralpha, IL-15Ralpha, and cytokine-induced proliferative responses of T cells in a cohort of HIV-infected pediatric patients and adults classified on the basis of immunologic and virologic response to antiretroviral therapy were examined. The studies indicated that patients had increased percentages of effector memory CD8+ T cells in comparison to healthy volunteers. While patients with partially controlled viremia and poor CD4 T cell reconstitution manifested poor proliferative responses to anti-CD3 or HIV gag antigen stimulation, proliferative responses to Cgamma chain utilizing cytokines IL-2, IL-7, and IL-15 were robust. Another Cgamma chain utilizing cytokine, IL-21 had no influence on cellular proliferation but enhanced perforin expression in effector CD8 T cells. Thus, cytokine receptor deficiencies may contribute to immune deficiency in HIV-infected patients, and Cgamma chain cytokines may play an important role in vivo in immune homeostasis in lymphopenic patients by maintaining the memory subsets of T cells in patients with CD4 T cell deficiency.

The Benign Lymphoepithelial Cyst and a Classification System for Lymphocytic Parotid Gland Enlargement in the Pediatric HIV Population

The objectives of this study are to present a series of parotid gland benign lymphoepithelial cysts (BLEC) in HIV-positive children and to propose a three-tiered classification system for HIV-associated lymphocytic parotid gland enlargement. The authors conducted a retrospective case series and literature review. The authors conducted a retrospective chart review of four pediatric patients with HIV-associated parotid gland BLEC who presented to a tertiary care university medical center. Four pediatric HIV-positive patients (four girls; age range, 7-17 years [mean age, 12.8 years]) were diagnosed with parotid gland BLEC. Two patients presented with acute parotitis and the others presented with asymptomatic enlargement of the parotid glands. Three patients had bilateral parotid gland BLEC. The other patient demonstrated persistent generalized lymphadenopathy (PGL) of the intraparotid and cervical lymph nodes and early BLEC limited to the left parotid gland. One patient also displayed parotid gland microcalcifications and cystic changes in the adenoids, neither of which have been described previously in the setting of HIV-associated BLEC. Computed tomography was performed on all patients, and one patient underwent fine needle aspiration to confirm the diagnosis. All patients opted for observation and antiretroviral medication therapy as long-term treatment. Based on these findings and a review of the literature, we propose a three-tiered classification system for lymphocytic parotid gland enlargement in the HIV population: 1) PGL, 2) benign lymphoepithelial lesions (BLEL), and 3) BLEC. This series equals the largest pediatric series of HIV-associated parotid gland BLEC in the English literature. One patient in our series also demonstrated PGL; there were no cases of BLEL. A classification system based on morphology is proposed to help resolve the confusion in terminology used to describe this entity. Most pediatric HIV-infected patients with parotid gland BLEC can be treated with observation and antiretroviral medication therapy. For others, who are symptomatic or more concerned about their cosmetic appearance, sclerotherapy may offer a reasonable option. Radiation therapy and surgery should be reserved for select cases.