The impact of HIV/AIDS on children in developing countries

HIV infection and AIDS among children continues to be a significant problem in developing countries despite the progress that has been made in HIV prevention and AIDS treatment elsewhere during the past two decades. The reasons for this difference are complex and multifactorial. They include the higher background prevalence of infection among adults in some communities in developing countries, the slow implementation in many countries of prenatal HIV screening programs and prophylaxis which can reduce the transmission to infants during labor and delivery, the social and health consequences of not breastfeeding, and the economic realities associated with expensive diagnostic testing and antiretroviral treatment. While the world waits for an effective HIV/AIDS vaccine, to reduce the prevalence of HIV in the community, public health programs need to continue to emphasize proven methods of HIV transmission prevention among groups with a high-risk of HIV acquisition, as well as provide counselling for the general population about personal protection and the provision of compassionate care for those affected.     

Clinical manifestations and management of pediatric HIV infection

HIV infection has emerged as a colossal problem with epidemic proportions. According to an estimate from UNAIDS about 36.1 million people all over the world are infected at present. In India about 3.5 million people are infected. The infection has evolved into phase II process of disease evolution, spreading from high-risk population to the general population. The antenatal HIV seropositivity has shown a steady increase from 0.1% to 2% in some tertiary care hospitals in Mumbai. Pediatric HIV infection presents with diverse clinical manifestations. In developing countries like India, diagnosis of infection during first year of life in perinatally exposed infants poses a problem due to lack of easy accessibility and increased cost of diagnostic facilities like HIV-PCR, CD4/CD8 counts and viral cultures. Moreover, lack of adequate drugs and exorbitant cost of sustaining antiretroviral therapy complicates the management issues. An assortment of antiretovirals is available in USA and other developed countries. In India drugs like zidovudine, lamivudine, stavudine, nevirapine and indinavir are available and are used in symptomatic patients. CDC has defined definite treatment guidelines for pediatric population recently. These guidelines need to be modified in our set up. At the present juncture in India the emphasis remains on the prevention and treatment of opportunistic infections like tuberculosis and pneumocystis carinii and on prevention of perinatal transmission with zidovudine. This brief review deals with various clinical manifestations as relevant in a developing country like India and recent advances in antiretroviral therapy.     

Recurrent ascites in an infant with perinatally acquired cytomegalovirus infection

We describe an infant with symptomatic perinatally-acquired cytomegalovirus (CMV) infection manifested by fever, anaemia, thrombocytopenia and hepatosplenomegaly. This infant developed recurrent episodes of severe ascites during which the virus was isolated from his urine. This rare hepatic manifestation of neonatal CMV infection has, to the best of our knowledge, only been reported twice in aborted fetuses with intrauterine systemic CMV infection.Abbreviation CMV cytomegalovirus     

IgG2 deficiency in children with human immunodeficiency virus infection

Infection with the human immunodeficiency virus (HIV) induces a polyclonal B-cell activation. Despite elevated serum immunoglobulin levels, a significant deterioration of the antigen specific humoral immune response exists in most cases. We studied the influence of HIV infection on the serum levels of IgG subclasses in children. We investigated 76 children (aged 15 months to 18 years) with HIV-1-infection. Most children (88%) showed elevated serum immunoglobulin levels. IgA (87%) and IgM (74%) were more often above normal levels for age than IgG (60%). IgG subclass serum levels were significantly altered. The increase in total IgG was mainly due to a marked augmentation of the IgG1 fraction. In most cases IgG3 was simultaneously elevated. Ten children (13%) had very low IgG4 levels (<0.03 g/l). Out of 61 patients older than 2 years 8 (13%) had a profound IgG2 deficiency with normal or elevated total IgG. Four of them also had low IgG4 levels (<0.03 g/l). A correlation between IgG2 deficiency and HIV infection according to the Centres for Disease Control classification for acquired immunodeficiency syndrome could not be demonstrated (three patients with symptomatic and five with asymptomatic infection).     

Epidemiology of HIV infection in children in Europe

In Europe the Human Immunodeficiency Virus (HIV) epidemic in children is an important public health problem. Reliable epidemiological information varies widely among countries, and there is no standard method to document the pandemia. By September 1992, a total of 81,849 AIDS cases were identified. France had 21,487, Spain 15,678 and Italy 14,784 (63% of all cases). The highest rate per 100,000 inhabitants occurred in Spain (88.9), France had 70.6 and Italy 63.5. The numbers of HIV⁺ newborns (NB) in Spain were 4673, in Italy 2,693, in Belgium 368, in Scotland 79 and in Holland 11. The highest rate of HIV⁺ NBs per 100,000 inhabitants occurred in Spain (120.1), the lowest in Holland (0.73). In Western Europe, 82% of all cases were due to vertical transmission. Mothers'venous drug use was the most common form of HIV transmission.     

Nutrition and HIV infection in children

HIV infection has profound effects on a patient’s nutritional status because it can modulate appetite, nutrient absorption and basal metabolic rate. In addition, HIV infection can lead to the depletion of a variety of vitamins and micronutrients including vitamins A, D, B₂, B₆, B₁₂, L-carnitine, iron, zinc and selenium. This review article summarizes existing data regarding nutritional defects in HIV-infected patients and the results of clinical studies addressing the effects of nutritional supplementation in infected patients.     

Association between steatorrhea, growth, and immunologic status in children with perinatally acquired HIV infection

OBJECTIVE: To examine the prevalence of steatorrhea and exocrine pancreatic insufficiency (EPI) and their association with growth and immune status variables in children with perinatally acquired human immunodeficiency virus (HIV) infection. DESIGN: Cross-sectional study. SETTING: Tertiary care HIV subspecialty practice. PARTICIPANTS: Children with perinatally acquired HIV infection. Exclusion criteria included being younger than 1 year and receiving mineral oil as a medication. METHODS: Weight, height, and upper arm anthropometric variables were measured. Spot stool samples were analyzed for steatorrhea using the Sudan III qualitative test and for EPI using fecal elastase-1 enzyme assay. Hormone-stimulated pancreatic function testing and 72-hour stool and dietary fat sample collection were performed when fecal elastase-1 enzyme was in the range of EPI, defined as less than 200 microgram/g. HIV RNA viral load, CD4 status, type of antiretroviral therapy, and biochemical evidence of hepatobiliary disease were measured within 3 months of stool sample collection. z Scores were computed for height, weight, triceps skinfold, and upper arm muscle area. RESULTS: We enrolled 44 patients (23 girls [52%]) with a mean +/- SD age of 7.4 +/- 3.1 years. None had hepatobiliary disease. The prevalence of steatorrhea was 39% (95% confidence interval, 23%-56%). The prevalence of EPI was 0% (95% confidence interval, 0%-9%). There were no associations between steatorrhea and EPI, growth, HIV RNA viral load, CD4 status, or type of antiretroviral therapy. Older children had decreased z scores for height (r = -0.42; P =.006). CONCLUSIONS: The clinical significance of steatorrhea in children with HIV infection is unclear. Furthermore, its evaluation should focus on nonpancreas-based conditions. Continual close monitoring of growth is essential in children with HIV infection.     

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.     

Autoimmune phenomena in children with Human Immunodeficiency Virus infection and Acquired Immunodeficiency Syndrome

We have studied sera from 44 children with Human Immunodeficiency Virus infection and Acquired Immunodeficiency Syndrome using immunoblotting, radioimmunoassay, enzymoimmunoassay and indirect immunofluorescence. We have detected a low incidence of antinuclear (2.9%), anti-reticulin (2.9%) and anti-smooth muscle (14.7%) antibodies by indirect immunofluorescence. By enzymoimmunoassay we have detected anti-dsDNA (20.5%) and anti-ENA [anti-nRNP (61.3%), anti-Sm (29.5%), anti-Ro (47.7%) and anti-La (18.1%)] antibodies. Tests for anti-dsDNA by radioimmunoassay were negative, suggesting the presence of low-avidity anti-DNA antibodies. By immunoblotting we have detected anti-C (nRNP) (33.3%), anti-BB' (Sm) (33.3%), anti-Ro (60 KD) (4.5%) and anti-La (11.3%) antibodies. The presence of anti-Ro antibodies was associated with progressive neurological disease. Long-term follow-up studies with larger numbers of patients are necessary to evaluate the clinical significance of the presence of anti-dsDNA and anti-ENA antibodies in children infected with Human Immunodeficiency Virus.     

Disclosure of HIV/AIDS diagnosis to HIV-infected children in Thailand

BACKGROUND: With the availability of highly active antiretroviral therapy, more HIV-infected children have lived longer. Many children are at the age that they should know the diagnosis. AIM: To identify the prevalence and patterns of disclosure of HIV/AIDS diagnosis to HIV-infected children. METHODS: A cross-sectional study was conducted among 103 main care givers of HIV-infected children aged > or =6 years who received highly active antiretroviral therapy at Chiang Mai University and Sanpatong district hospitals, northern Thailand. RESULTS: One-third (30.1%) of the children knew their HIV/AIDS status at an average age of 9.2 years. The care givers' understanding of 'knowing' did not always mean that the children were told the name of 'HIV' or 'AIDS'. Many of those care givers (84.3%) who reported that the child did not know their diagnosis had inaccurately explained to the child that he or she had some kind of disease such as allergy, lung, or liver disease. The most common reason for non-disclosure was the fear that disclosure might have negative psychological consequences to the child (53.4%). Almost all (88.7%) agreed that they should tell the children their diagnosis in the future but half needed health-care providers to help them at the event. CONCLUSION: There is a need for the development of disclosure guide-lines and models for health-care providers and care givers as there was a high rate of inaccurate disclosure and, in addition, care givers expressed their need for assistance from health-care providers for the future disclosure.     

Italian guidelines for antiretroviral therapy in children with human immunodeficiency virus-type 1 infection. Italian Register for HIV Infection in Children

Human immunodeficiency virus-type 1 (HIV-1) infection and its treatment are peculiar in children. Adherence and compliance must be carefully taken into account before initiating or changing therapy and in the choice of drugs. Even in the absence of paediatric-specific trial results and notwithstanding drug-labelling notations, all antiretroviral drugs should be used when indicated. A combined therapy is compulsory. Therapy is highly recommended in category C or category 3 and recommended in category B children. Indications in categories N1, N2, A1 or A2 are limited. A triple association is recommended in category C or category 3 children or in those with a high viral load, when compliance is guaranteed. A step-down strategy is not advisable. Infants'treatment should be inserted into controlled studies. Therapy should be changed when serious side effects or poor tolerance (choose drugs with a different toxicity and greater tolerance), poor compliance (individualize the motives) or treatment failure (evaluate progression and adherence) occurs.     

Personnel costs and perceived benefit of telephone care in the management of children with type 1 diabetes

Intensive management of patients with type 1 diabetes improves control and reduces rates of long-term complications. Telephone care as an adjunct to office visits is important in the management of children with type 1 diabetes in pediatric endocrine practices in the USA. The goal of this project was to assess the personnel costs and patients' perceptions of telephone care in a moderately sized pediatric diabetes care center (301 patients with a diagnosis of type 1 diabetes). There were two parts to this study. First, telephone logs were kept by three pediatric endocrine nurses (2.2 full-time equivalents [FTEs]) and three pediatric endocrinologists (2.0 FTEs) for two 1-wk blocks. Computerized databases were used to determine the number of clinic visits in 1998. Second, a survey assessing the frequency, perceived value and consequences of phone contact with the diabetes team was distributed to 40 families at clinic visits. Mean nurse/certified diabetes educator (CDE) time spent on the phone was 12.1 h/wk, with an additional 9.7 h/wk spent preparing and documenting. Physicians spent 6.4 h/wk on the phone, and 6.1 h/wk preparing/supervising/documenting. For our 301 patients with diabetes, the weekly personnel cost for telephone care at our institution was 1367 US dollars or 236 US dollars/patient/yr. Of the families surveyed, 80% reported that they had used the phone to obtain care for their child with diabetes and 55% had paged the doctor on call in the previous 6 months. Seven patients reported that phone contact prevented a total of 13 emergency department (ED) visits and 35 office visits. Using a cost estimate of 550 US dollars per ED visit, and 103 US dollars per office visit, the cost of prevented visits was 232 US dollars/patient/yr in our center. These data indicate that telephone care is effective in reducing the cost of reimbursable care via the ED and office visits, as well as avoiding hospitalization. However, the cost of providing this telephone care is not reimbursable to providers.     

Clinical practice treatment of HIV infection in children

Perinatal transmission remains the main cause of HIV infection in the pediatric population. Treatment of HIV-infected children has become less of a problem in resource-rich countries with a remarkable decrease of perinatal infections, resulting in an effective prevention of mother-to-child transmission and antiretroviral treatment of HIV infection in pediatrics because of differences in drug pharmacokinetics, the lack of available licensed drugs, the use of different immunologic markers and age-related adherence issues. This review, for the general pediatrician, summarizes the most recent pediatric data and guidelines for treatment of HIV. Recommendations for when to initiate therapy are more aggressive in children than in adults, particularly in infants because disease progression in children is more rapid. The indications to start therapy differ by age and are based on international immunologic and clinical classification system for HIV infection. At present, combination regimens of at least three drugs are recommended. Moreover, therapies must also consider the potential complications in these children currently treated for a long time.