Correlation of CD4 count, CD4% and HIV viral load with clinical manifestations of HIV in infected Indian children

AIM: To correlate the absolute CD4 count, CD4% and HIV viral load with different clinical manifestations of HIV in antiretroviral-naive children. SETTING: The paediatric and perinatal HIV clinic in a tertiary care hospital over a period of 4 years, from January 1999 to December 2003. MATERIALS AND METHODS: A total of 92 highly active antiretroviral-naive, HIV-1-infected children were enrolled in a cross-sectional study. The clinical manifestations, age, sex and CDC classification of each patient were determined. CD4 count, CD4% and HIV-1 viral load were estimated at presentation and correlated with various clinical manifestations of HIV disease. RESULTS: CD4% was higher in infants (p < 0.001) and lower in children over 5 years of age (p = 0.01). Boys had a higher absolute CD4 count than girls (769 +/- 517 vs 532 +/- 430 cells/mm3, p = 0.02). Patients with lymphadenopathy (n = 43) had a high CD4 count (840 +/- 487 cells/mm3, p = 0.01) whereas patients with HIV cardiomyopathy (n = 4) had low CD4 counts (mean 182 cells/mm3, p = 0.04). In patients with failure to thrive (n = 29), the CD4% was low (14 +/- 9%, p = 0.02) and HIV-1 viral load was high (mean 4.5 x 10(5) copies/ml, p = 0.03). CD4 count, CD4% and HIV viral load did not correlate with the stage of the disease as per the CDC classification. CONCLUSION: HIV viral load, CD4 cell count and CD4% vary with age and disease complications in HIV-infected children. However, CD4 count, CD4% and viral load did not correlate with CDC classification.     

Acute poststreptococcal glomerulonephritis: a manifestation of immune reconstitution inflammatory syndrome

Immune reconstitution inflammatory syndrome (IRIS) is a well-described complication of initiation of highly active antiretroviral therapy in HIV-infected patients. As the immune system recovers, an inappropriate inflammatory response often occurs that causes significant disease. It is most commonly seen in patients na?ve to therapy with CD4+ T-lymphocyte counts <100 cells/cmm and usually presents as a flare of mycobacterial, cytomegalovirus, or herpes zoster infections. Less commonly, this syndrome occurs in response to noninfectious triggers and results in autoimmune or malignant disease. Here we present the first case of acute poststreptococcal glomerulonephritis associated with varicella zoster virus and IRIS in an adolescent with perinatally acquired HIV and hepatitis C virus infections. Our patient was not na?ve to therapy but was starting a new regimen of therapy because of virologic failure and had a relatively high CD4+ T-lymphocyte count. This case report indicates that IRIS remains a concern after initiation of a new highly active antiretroviral therapy regimen in HIV-infected patients with high viral loads, even in the presence of CD4+ T-lymphocyte counts >100 cells/cmm. It may present as infectious, malignant, or autoimmune conditions including poststreptococcal glomerulonephritis.     

Randomized controlled trial of short-term withdrawal of i.v. immunoglobulin therapy for selected children with human immunodeficiency virus infection

BACKGROUND: The aim of the present paper was to determine whether monthly i.v. immunoglobulin (IVIG) could be safely discontinued in antiretroviral-treated human immunodeficiency virus (HIV)-infected children. METHODS: In a double-blind cross-over trial, children < or =18 years with HIV infection, well controlled on antiretroviral therapy, were randomized to alternating courses of 3 consecutive months of IVIG (400 mg/kg once a month) and 3 consecutive months of placebo for 1 year. The primary outcome was days of fever per month. Secondary outcomes were frequency of serious infections, changes in HIV viral load (VL), CD4+ counts and IgG levels. RESULTS: Fifteen children were enrolled. Using the revised pediatric HIV clinical classification system of the Centers for Disease Control and Prevention, eight were severely symptomatic (C), four were moderately symptomatic (B) and three were mildly symptomatic (A). There were no statistically significant outcome measures. The mean number of days of fever per month with IVIG versus placebo was 0.55 days versus 1.48 days (P = 0.11). The difference was 0.9 days (95% confidence interval: +2.05 to -0.25). There were no serious infections in either period. For the IVIG versus placebo periods, mean CD4 counts were 970 cells/microL versus 906 cells/microL (P = 0.12), VL 2.90 log(10) copies/mL versus 2.82 log(10) copies/mL (P = 0.70) and IgG levels were 17.41 g/L versus 16.6 g/L (P = 0.13). CONCLUSION: In antiretroviral-treated HIV-infected children short-term withdrawal of monthly IVIG was not associated with a significant increase in incidence of infections or a decline in immunologic function (CD4 count, viral load and IgG levels). These results suggest that monthly IVIG can be safely discontinued in HIV-infected children who are clinically stable and receiving combination antiretroviral therapy.     

Homeostatic role of IL-7 in HIV-1 infected children on HAART: association with immunological and virological parameters

AiM: To investigate the role of IL-7 in HIV-infected children on highly active antiretroviral therapy (HAART) and its association with laboratory parameters related to disease progression. PATIENTS AND METHODS: A cross-sectional study in 31 vertically HIV-infected children (median age 8.4 y) treated with HAART, and a longitudinal study in four of those same children was carried out. In both studies, viral load, CD4+ T-cell counts, thymic production of T cells by TCR rearrangement excision circles (TRECs), IL-7 plasma levels and viral phenotype were determined. RESULTS: IL-7 levels were higher in HIV-infected children than in age-matched, uninfected controls. In addition, HIV children with CD4+ T cells between 200 and 500 T cells/mm3 had higher IL-7 levels and lower TREC values than HIV-infected children with CD4+ T cells >500 T cells/mm3. IL-7 levels were higher in children with syncytium-inducing (SI) phenotype than in those with non-syncytium-inducing (NSI) variants. During the follow-up of four HIV children, the decrease in viral load after HAART was always associated with a recovery of CD4+ T cells and TRECs, which was followed by a decrease in IL-7 returning to the levels present prior to the drop in CD4+ T cells. The four HIV-infected children had SI/X4 isolates in PBMC before HAART, and the viral phenotype switched to NSI/R5 after HAART. CONCLUSION: Our data suggest that IL-7 plays a key role in the maintenance of T-cell homeostasis in HIV-infected children on HAART, both through peripheral expansion and through a thymus-dependent mechanism.     

Acquired immunodeficiency syndrome in children: pathogenesis, prognostic markers, and treatment

OBJECTIVE: To review recent knowledge about Acquired Immunodeficiency Syndrome in children to help pediatricians provide care for these patients.METHOD: We reviewed the most recent papers about pathogenesis, prognostic markers and treatment of the HIV- infected child.RESULTS: We present the main HIV features that may interfere in the pathogenesis of this syndrome and that should be taken into consideration when the antiretroviral therapy starts.CONCLUSIONS: Viral replication in children is very intense, and the persistence of high levels of viral load may be a sign of immunological immaturity. Viral load measurement and CD4+ lymphocytes count are important markers of the disease progression. At least two drugs should be administered as antiretroviral therapy, which should aim at reducing the viral load to undetectable levels. This will slow down the progression of the disease and the emergence of resistant viral strains.     

高效抗逆转录病毒治疗对艾滋病患儿CD8+T细胞活化分子CD38和人类白细胞抗原DR表达水平的影响及其与病毒载量的关系

目的 观察高效抗逆转录病毒治疗(HAART)对我国艾滋病患儿CD8+T细胞活化标志分子CD38和人类白细胞抗原DR(HLA-DR)表达水平的影响及其与病毒载量的关系.方法 对194例接受HAART的艾滋病患儿进行横断面研究,用流式细胞术检测CD4+、CD8+T细胞数,以及CD8+/CD38+和CD8+/HLA-DR+T细胞比例,RT-PCR检测血浆HIV RNA载量.并检测52名健康儿童CD8+/CD38+和CD8+/HLA-DR+T细胞比例作为正常对照.结果 本组中,135例病毒载量＜400 copies/ml,59例病毒载量≥400 copies/ml.病毒载量≥400 copies/ml组CD8+/CD38+T和CD8+/HLA-DR+T细胞水平显著高于病毒载量＜400 copies/ml组,差异有统计学意义(29.6±10.1 vs19.9±9.8;17.7±6.4 vs 9.6±6.1,P＜0.05);病毒载量＜400 copies/ml组,CD8+/CD38+T细胞接近正常水平,而CD8+/HLA-DR+T细胞仍高于正常水平,差异有统计学意义(19.9±9.8 vs 15.6±9.0;9.6±6.1 vs 5.8±3.3,P＜0.05).CD8+/CD38+和CD8+/HLA-DR+T细胞百分比均与病毒载量成正相关(前者相关系数R=0.403,P=0.03,后者相关系数R=0.569,P=0.09).结论 艾滋病患儿CD8+T细胞活化程度与病毒载量成正比,有效的HAART治疗能够显著地降低HIV感染者免疫活化程度,CD8+/CD38+和CD8+/HLA-DR+T细胞百分比可能是资源有限地区替代病毒载量检测的潜在指标.

Abstract：

Objective To study the expression of CD38 and HLA-DR on CD8 + T cells in pediatric AIDS patients receiving highly active antiretroviral therapy (HAART) and the relationship of immune activation and disease progression. Methods A cross-section study of 194 pediatric AIDS patients receiving HAART was carried out and 52 age-matched healthy children were recruited as control. The percentage of CD4+ , CD8+ , CD8+/CD38 + and CD8+/HLA-DR+ T cells was tested using flow cytometry, and HIVRNA in plasma was detected by quantitative RT-PCR. Results One hundred and ninety-four pediatric AIDS patients were divided into two groups according to the viral load: 59 patients with VL≥400 copies/ml and 135 patients with VL＜400 copies/ml. The percentage of CD8 +/CD38+ and CD8 +/HLA-DR+ T cells of patients with VL≥400 copies/ml was significantly higher than that of patients with VL ＜ 400 copies/ml (P ＜ 0. 05 ). Of patients with VL ＜ 400 copies/ml, the percentage of CD8 +/CD38 + T cells was nearly normal, and the percentage of CD8 +/HLA-DR+ T cells was higher than normal level ( P ＜ 0. 05 ). There was a positive correlation between percentage of CD8+/CD38+ and of CD8 +/HLA-DR+ T cells and viral load ( R = 0. 403, P = 0. 03 for the former and R = 0. 569, P = 0. 09 for the later). Conclusions Effective HAART could decrease immune activation of HIV-infected children significantly. And there was a positive correlation between percentage of CD8 +/CD38 + and of CD8 +/HLA-DR + T cells and viral load, suggesting that the two indicators might be used as the substitution of viral load in resource-limited areas.     

IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.     

Intravenous immunoglobulin in HIV-I infected haemophilic patients.

In order to evaluate the efficacy of intravenous immunoglobulin (IVIG) in the early stages of HIV infection (patients without AIDS or AIDS related complex) a prospective controlled open trial was conducted in 36 patients (age 6-19 years) with haemophilia. Eighteen patients received 0.3 g/kg IVIG at two week intervals; 18 patients served as controls. Major criteria for the evaluation were progression of HIV disease assessed by the modified Brodt/Helm classification, number of infectious events and HIV associated thrombocytopenia, and the CD4+ T cell count. After 24 months of evaluation seven patients in the IVIG group and five patients in the control group deteriorated according to their staging, with one patient in each group developing AIDS. Thrombocytopenia and infectious events, but no severe bacterial infections, occurred in both groups in similar numbers. The absolute CD4+ T cell count decreased by 284/microliters in the IVIG group and by 143/microliters in the control group respectively (mean values). The statistical analysis of these criteria did not reveal any significant difference. In conclusion, IVIG was not effective in the early stages of HIV infection in patients with haemophilia. IVIG did not slow down the progression of HIV disease and did not prevent the development of an immunodeficiency as assessed by the CD4+ T cell count.     

Infection à VIH de l''enfant : quand débuter le traitement antirétroviral ?

Administration of highly active antiretroviral treatment (HAART) has led in the developed world to a dramatic reduction in the incidence of HIV related pediatric mortality. HAART is now the standard-of-care therapy in infected children but the occurrence of short- and long-term drug-related toxic effects and emergence of drug-resistant viral variants temper its success. In children, both CD4 cell percent and viral load have independent predictive value for disease progression, CD4 cell being the stronger predictor of AIDS and death. Concerning children aged 12 months or oder current French recommendations for immediate therapy are based on the presence of clinical symptoms (of categories B or C) or the occurrence of a severe immunodeficiency (CD4 cell percent < 15%). In infants, risk of disease progression is higher and the viral load and CD4 percent are less reliable markers. HAART should theoretically be initiated in all infants in order to prevent HIV encephalopathy and early death. However, viral failure under HAART is often encountered in children less than 12 months because of high levels of replication as well as limited data on pharmacokinetics and drug dosing. A possible alternative approach for infants without risk factor for early progression is to defer HAART under close mentoring.     

Correlation of serum antigen and antibody concentration with clinical features in HIV infection.

Serum antigen and antibody values were studied in 164 infants and children infected perinatally with HIV. HIV antigens p17, p24, gp41, and gp120 were determined in sera by immunoblot and antigen capture assays. Lymphocyte blast transformation, serum immunoglobulins, and circulating immune complexes were also evaluated. Altogether 50 patients had HIV antigens measured: 31 (62%) patients had p17 antigen in the serum and 29 (58%) had p24 antigen present. In 19 (38%) and nine (18%) patients, respectively, gp120 and gp41 were detected. All four HIV antigens were detected in seven (14%) patients. There was a positive correlation between the concentration of each HIV sequential specimens were outcome. When sequential specimens were analysed, 120 (73%) patients had p24 antigen present. Patients with stage P2B and P2D (Centers for Disease Control classification) had the highest concentrations of p24 antigen with a mean of approximately 200 pg/ml. Altogether 70% of patients with a p24 antigen concentration of greater than 30 pg/ml eventually died or had severe clinical disease within six to 24 months. Infants under 15 months of age with a p24 antigen concentration as low as 5 pg/ml also did poorly. Increased immunoglobulins and decreases in mitogenic responses and absolute CD4+ lymphocyte counts were more prevalent in patients with raised p24 antigen. Raised concentrations of circulating immune complexes were seen in the symptomatic phase of the disease whereas in the terminal stage of the disease raised serum antigen and a decrease in circulating immune complexes and absolute CD4+ lymphocyte count were evident. Loss of p24 and/or p17 antibody as well as a decreasing ELISA optical density for HIV antibody also signalled progression of the disease.     

T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents: retention of naive T lymphocytes in HIV-infected adolescents. The Adolescent Medicine HIV/AIDS Research Network

BACKGROUND: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. OBJECTIVE: To assess lymphocyte subsets in HIV-infected and high-risk HIV-negative adolescents. DESIGN: The Reaching for Excellence in Adolescent Care and Health Project of the Adolescent Medicine HIV/AIDS Research Network recruits a cohort of HIV-infected and high-risk HIV-uninfected adolescents, aged 13 to 18 years 364 days, into a study of biomedical and behavioral features of HIV infection as seen in the context of full availability of primary care and HIV-related consultative services. Lymphocyte phenotypes were determined using standard 3-color flow cytometry. SETTING: The Reaching for Excellence in Adolescent Care and Health Project is carried out at 16 clinical sites in 14 urban areas. PARTICIPANTS: T-lymphocyte subsets are reported in 192 HIV-positive and 78 HIV-negative youths. RESULTS: For HIV-positive subjects, the total CD4+ cell count and the percentage of CD4+ cells are decreased when compared with those of the HIV-negative controls (P<.001). The reduction in total CD4+ cells reflects a loss of naive, and memory, CD4+ cells compared with HIV-negative youths. Human immunodeficiency virus-infected adolescents, many of whom have been infected recently (ie, those with CD4+ cell counts > or =0.500 x 10(9)/L [500/microL]), have a significant increase in naive CD8+ cells compared with HIV-negative youths (P<.01). There also is a significant increase in memory CD8+ cells at all strata of total CD4+ cells compared with HIV-negative youths (P<.01). The increase in naive CD8+ cells in those subjects with CD4+ cell counts of 0.500 x 10(9)/L or greater is a unique finding in this cohort. CONCLUSIONS: This study demonstrates high levels of naive CD8+ cells in response to HIV infection in adolescents with CD4+ cell counts of 0.500 X 10(9)/L or greater. The presence of high levels of naive CD8+ cells suggests functioning thymic tissue in some adolescents infected with HIV. Furthermore, the normal level of naive CD4+ cells in adolescents with CD4+ levels of 0.500 x 10(9)/L or greater provides additional support for the concept of a more robust immune system in HIV-infected adolescents compared with HIV-infected adults. These observations suggest that the immune system of HIV-infected adolescents may be capable of better responses to neoantigens and cytotoxic T-lymphocyte responses to HIV than the immune system of infected children or adults. Human immunodeficiency virus-infected adolescents may have an immune system that is capable of reconstitution following highly active antiretroviral therapy.     

Natural history of HIV infected pediatric long-term or slow progressor population after the first decade of life

BACKGROUND: Perinatally infected long-term nonprogressors/slow progressors represent a select group of individuals. There is very limited information on this group of children beyond the first decade of life. A group of HIV-infected long-term nonprogressor/slow progressor children was studied. METHODS: We enrolled 20 HIV-infected adolescents who were receiving no or minimal therapy (defined as single or dual nucleoside therapy) before the age of 10 years and who had maintained CD4 counts above 25% for the first decade of life. We analyzed immunologic and virologic characteristics. Thymic receptor excision circles (TREC) were measured on stored frozen peripheral blood mononuclear cells. CD4 count, viral load and other pertinent information including race and age were obtained from individual medical records. RESULTS: Nine of the 20 patients recruited were noted to have developed falling CD4 counts at or around puberty, whereas the other 11 remained stable. There was no difference in TREC values or HIV RNA values before or after puberty between the 2 groups of patients. Those who remained stable, in terms of maintaining CD4 T cells as a group had falling viral loads with age. Those whose CD4 values declined after puberty had viral loads that did not decrease with age. CONCLUSION: A select group of patients who never received HAART during their first decade of life will continue to maintain good CD4 associated with declining HIV RNA values. Thymic output is not predictive of those that don't maintain CD4 T cells.     

Thymic size on chest radiograph and rapid disease progression in human immunodeficiency virus 1-infected children.

BACKGROUND: Early infection of the thymus, an organ central to the ontogeny of the immune system, has been proposed as a cause of rapid progression in pediatric HIV disease. OBJECTIVE: To test the hypothesis that small thymic volume is associated with rapid disease progression in HIV-infected children. DESIGN: Three pediatric radiologists established criteria for rating the size of the thymic profile on chest radiographs. All available baseline chest radiographs were reviewed in a random sequence, with radiologists blinded to study subjects' clinical status. A consensus was reached on whether the thymus was normal or small for age. SETTING: A prospective multicenter study of the natural history of HIV-1 infection in children, the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted Human Immunodeficiency Virus Infection (P2C2) Study. PATIENTS: Fifty-eight HIV-infected children and 38 control children (uninfected but born to HIV-infected women) for whom chest radiographs in the first year of life were available. MAIN OUTCOME MEASURE: Rapid progression of HIV disease, defined as CDC Clinical Category C (severely symptomatic) or Immunologic Category 3 (severe immunosuppression) by 1 year of age. RESULTS: The mean age at the time of chest radiography was 3.5 months. Ten (17%) HIV-infected children had reduced thymic profile size, whereas no controls did (P = 0.006). Of the 58 (59%) HIV-infected children 34 were classified as rapid progressors, and 9 (26%) of them had reduced thymus size, compared with 1 (4%) of the non-rapid progressor children [odds ratio, 8.28; 95% confidence interval (CI), 1.0, 70.5; P = 0.035]. Baseline mean CD4+ count was 1642 (95% CI 1322 to 2009) cells/microl for those with normal thymus and 740 (95% CI 380 to 1275) cells/microl for those with reduced thymus (P = 0.007). CONCLUSION: Early thymic involution is associated with rapidly progressive disease in HIV-infected children.     

Relevance of viral phenotype in the early AIDS outcome of pediatric HIV-1 primary infection

In infants the clinical course of HIV-1 infection is bimodal, differing considerably from that of adults. The effect of HIV-1 phenotypic features and plasma viral load on the clinical course of infection has been well established in adults, whereas in children it remains controversial. The aim of this study was to prospectively evaluate the effect of HIV-1 replication phenotypes during the first year of primary infection in the development of premature immunosuppression and early pediatric AIDS. In 62 vertically infected children replication rates of HIV-1 isolates from primary cultures and syncytium-inducing capability in MT-2 cell line were evaluated, together with plasma viral load. It was observed that rapid replication rate and syncytium-inducing phenotype accelerate the early onset of pediatric AIDS (p = 0.02 and p = 0.04, respectively). Rapid replication kinetics was the only significantly independent variable for early clinical outcome (risk ratio, 2.48; p = 0.02). Both viral properties contributed to rapid CD4+ T-cell depletion (p = 0.05 for rapid replication rate, p = 0.01 for syncytium-inducing viral phenotype). Plasma viral burden higher than 5.5 log(10) copies/mL after 6 mo of age tended to be associated with disease progression. In conclusion, initial HIV-1 biologic features in pediatric primary infection by vertical transmission may influence the progression to early immunosuppression and development of AIDS.     

Immunological manifestations of HIV-infected children

This cross-sectional study of stable HIV-infected children was designed to document the immunological manifestations of paediatric HIV infection and to determine whether inexpensive markers of immunosuppression could be identified. Investigations included lymphocyte count and subset analysis, levels of total protein, albumin, immunoglobulins, beta-2 microglobulin and neopterin. The median age of the 74 children studied was 16.5 months and 76% and 39% had subnormal percentage CD4+ counts and absolute CD4+ counts, respectively. According to the Centers for Disease Control (CDC) guidelines, 85% were moderately or severely immunosuppressed. The majority had elevated neopterin, beta-2 microglobulin, IgG, IgM and IgA concentrations. The IgG concentration correlated positively with total globulin, IgG1 and IgG3 concentrations. On bivariate analysis, the absolute CD4+ count correlated positively with total lymphocyte count (r = 0.28 < 0.48 < 0.64) and negatively with total IgG concentration (r = -0.47 < -0.27 < -0.04), IgG1 concentration (r = -0.51 < -0.31 < -0.08), and neopterin concentration (r = -0.49 < -0.28 < -0.04). There was no correlation between CD4+ count, total globulin or beta-2 microglobulin concentration. On multiple linear regression analysis only the total lymphocyte count correlated with CD4+ count. Furthermore, on bivariate analysis total lymphocyte count correlated positively with absolute CD8+ count (r = 0.82 < 0.88 < 0.92). In conclusion, although there was a positive correlation between absolute CD4+ count and total lymphocyte count, the clinical significance is questionable as the total lymphocyte count correlated more strongly with the absolute CD8+ count.     

Disruption in cytokine and chemokine production by T-cells in vertically HIV-1-infected children

This study measured cytokine production by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) from 55 human immunodeficiency virus (HIV)-infected children born to HIV-infected mothers, and compared it with vertically exposed but uninfected age-matched children. A significant defect was observed in Th1 cytokine production [interferon-gamma and interleukin-2 (IL-2)] in HIV-infected children compared with controls, but without a concomitant increase in Th2 cytokines. Indeed, IL-5 and IL-10 production was even lower in HIV-infected children than in controls, with the decrease in IL-5 being the best predictive marker of immunodeficiency. In addition, an increased release of tumour necrosis factor-alpha (TNF-alpha) that correlated well with CD4+ levels, and a positive correlation of the TNF-alpha/IL-10 ratio with disease progression was observed. A correlation between AIDS-free status and higher %CD4+ and %CD8+ T-lymphocytes and RANTES (regulated on activation, normal T-cell expressed and secreted) production was also found. Conclusion: A dysfunctional cytokine production of PBMCs was observed in HIV-infected children in both Th1 and Th2 cytokines due to quantitative and qualitative defects induced by HIV-1. An important observation was an increased RANTES production associated with viral isolates of NSI/R5 phenotype and S/L kinetics.