The US Centers for Disease Control and Prevention (CDC) issued a report on the number of children diagnosed with AIDS after the Public Health Service recommended 1) use of zidovudine to reduce perinatal transmission of HIV and 2) that testing and counseling for HIV become part of routine prenatal treatment. The CDC found that the number of children with HIV/AIDS apparently peaked at 905 in 1992 and the number of those infected perinatally declined 27% by 1996. This encouraging news is shadowed by the facts that the number of cases of AIDS caused by heterosexual contact has increased by 10% in women and 5% in men women made up 7% of the reported new cases of AIDS in 1985 and 17% in 1995 most cases now involve Blacks and Hispanics and an increasing number of cases are being reported in the southern states. Meanwhile 50% of the 2.7 million new cases of HIV reported worldwide occurred in women and 40000 of the new cases reported in 1996 occurred in children. Most of the new cases of HIV in the developing world are linked to heterosexual transmission and the epidemic is unabated in some areas such as India Thailand and Africa. Increases were found in women and adolescents in South America and the Caribbean. Much work also remains to be done in the US to reduce the number of women infected and strengthen the protocol to prevent perinatal transmission while offering pregnant women continued therapy. Globally efforts must be made to prevent transmission especially in settings where therapies are not available and to develop a simple accessible inexpensive easy and effective intervention to prevent perinatal transmission.
BACKGROUND The purpose of this study is to (1) describe client and maternal demographic, social, and medical characteristics of pediatric clients receiving medical and social services at Ryan White (Title IV) program sites, and (2) determine the impact of on-site social work services in documenting client and family-related information used to assess the psychosocial needs of the families affected by human immunodeficiency syndrome and acquired immunodeficiency syndrome (HIV/AIDS). METHODS We studied infants born to known HIV-infected women who received HIV-related medical services at a federally funded Title IV Ryan White CARE Act provider site in Maryland. Eligibility criteria included < 24 months of age at time of initial clinic visit, a history of birth to a known HIV-infected woman, and a minimum of one comprehensive clinical visit for medical evaluation at a selected Title IV provider site. Study populations were categorized into three independent clinic cohorts. A pre- and postintervention study design was used to assess the impact of the intervention (i.e., on-site social work activities) on variables of interest. Clinic cohorts were (a) preintervention group (N = 181), from January 1, 1986 to December 31, 1989; (b) initial postintervention group (N = 216), from January 1, 1991 to December 31, 1992; and, (c) long-term postintervention group (N = 197), from January 1, 1993 to March 1, 1994. Client and maternal demographic, social, and medical information were recorded and statistical comparisons between pre- and postintervention clinic cohorts were completed with the use of standard statistical methods. RESULTS Pediatric clients were predominantly African American (94%), lived in low-income family units reflected by the prevalence of public assistance programs (i.e., Medicaid), had a high likelihood of Medicaid enrollment (> 80%), and reported a high frequency of social disruption (e.g., protective services interventions and housing difficulties). Greater than half of all medical records documented the "mother" as the client's primary caregiver in the three cohorts (a,b,c, above) pre- and postintervention cohorts, 51%, 65%, and 66.5%, respectively. Over two-thirds of the mothers among all cohorts were reported to have a current or past history of illicit drug use or alcohol abuse, 69%, 62%, and 67.5%, respectively. Postintervention groups, both initial and long term, were significantly more likely than the preintervention group to have documented medical record information relevant to a history of protective services, housing problems, and maternal demographic, social, and clinical information. Maternal HIV-related clinical status and select social factors (e.g., drug use, housing) remained underreported in both postintervention groups. CONCLUSIONS Title IV pediatric clinical sites deliver services to a predominantly urban, poor, minority community-the population at greatest risk for pediatric HIV-infection in Maryland. Alternative family members as the primary caregiver for infants and children was common and increased over time. These findings demonstrate that Title IV funded programs have been successful in the documentation of valuable client and maternal information necessary for the development of family-centered clinical and support services to a highly vulnerable population of HIV at-risk or infected infants and children in Maryland.
The objectives of this study were to compare the costs and benefits of recombinant human erythropoietin (r-HuEPO) relative to repeated transfusions in the treatment of zidovudine (AZT)-related anemia among HIV-infected children. The study was based on a tertiary care Canadian Pediatric Hospital Model. A decision analytic structure was used for the evaluation of cost-effectiveness. The decision tree involved two options. In option A:r-HuEPO, subjects receive r-HuEPO three times weekly at home for 1 year, whereas in B:no r-HuEPO, transfusions are given on a monthly basis in a medical short-stay unit over a 1-year period. Probabilities of various outcomes and downstream events were obtained from a literature review. The analysis was conducted from the perspective of the health-care system and utilized standard cost-effectiveness methodology. The results indicated that for every child receiving r-HuEPO, the total cost is Can $11,245 for 1 year compared with $3,130 per year for those in B:no r-HuEPO. The incremental cost effectiveness of A:r-HuEPO relative to B:no r-HuEPO is $1,373 per transfusion episode averted. The order of magnitude of the results was not significantly affected by changes in any of the assumptions used for the cost estimates or baseline probability values.
To characterize the cellular basis of IgE responses in HIV-positive (HIV+) children, we obtained central (bone marrow [BM], thymus) and peripheral (Peyer's patches [PP], mesenteric [MLN], and other lymph nodes [OLN], spleen), lymphoid organs from two children with AIDS (females, 2 and 8 years old), and from a non-HIV-infected trauma victim (female, 5 years old) at autopsy. PP were obtained from one of the HIV+ children (2 yr old) and from the non-infected child, but no PP were detected in small intestine of the 8-yr-old HIV+ child. Numbers of lymphocytes bearing surface IgE, CD19, CD3, CD4, and CD8 in lymphoid organs were determined (flow cytometry) and evaluated for expression of epsilon-specific (E) mRNA (RT-PCR). Thymus and MLN of the HIV+ child without PP contained high numbers of IgE+ (34% and 41%, respectively) and CD19+ (32% and 28%, respectively) cells; IgE+ cells were not found in any other organ. In contrast, in the HIV+ child with PP, IgE+ cells were detected in all organs, except BM. The thymus of this child contained fewer CD19+ cells (7%). However, in both HIV+ children, all lymphoid organs, including thymus, contained E mRNA. Because numbers of IgE+ cells often far exceeded numbers of CD19+ B cells, and because CD8+ T cells predominated in all organs, some of the IgE+ cells were probably CD8+ T cells with cytophilic IgE and may include IgE-specific regulatory and/or memory T cells. IgE responses were not detected in the healthy trauma victim nor were B cells found in thymus. The data suggest that during HIV infection, IgE+ B cells may be found in thymus and that synthesis of IgE may occur in all lymphoid organs except BM.
PURPOSE:The efficacy of zidovudine (ZDV) in patients with HIV-1 infection may decrease over time due to its decreased activation. The objectives of this study were to determine ZDV concentrations in plasma, active phosphorylated zidovudine (pZDV) concentrations in mononuclear cells, and assess the markers of immune function and drug toxicity during extended therapy.METHODS:Pediatric patients (aged 3 months to 18 years) with HIV-1-infection were enrolled in the study. For each patient, one blood sample was collected at each of eight routine visits to measure plasma ZDV and ZDV concentrations by a radioimmunoassay. Data including demographic information, immunological markers (CD2+, CD3+, CD4+, CD5+/19+, CD8+, CD16+, CD19+, CD38+/8+ lymphocytes), hematologic function (absolute neutrophil count, white blood cell with differential, hemoglobin, and red blood cell count), concurrent medications, and dosage regimens were obtained.RESULTS:The data from 13 patients were as follows: age: 2-18 years; range of ZDV dose: 76-238 mg/m2, total ZDV daily dosage: 264-720 mg/m2; duration of ZDV therapy prior to study: 1 to 37 months; time in study: 180-394 days; plasma ZDV concentration range: 5-1021 ng/ml; and pZDV concentration range: 0-5.382 pmol/10(6) cells. Both plasma ZDV and intracellular pZDV concentrations had a marked inter- and intrapatient variability. The pZDV concentrations decreased significantly over time in one pediatric patient (p < 0.05), tended to decrease but not significantly in three patients, and no decrease was detected in nine patients due to high variability. In our population, neither immunological nor drug toxicity markers changed over time.CONCLUSIONS:Marked inter- and intrapatient variability in pZDV concentrations was observed. The ability to phosphorylate ZDV, however, did not appear to change significantly in 12 of 13 pediatric patients with HIV-1 infection during the study period of 6-13 months.
This report describes the absence of neuropsychologic change observed over a 2-year period for 25 HIV-seropositive (HIV+) children and adolescents with hemophilia and 33 HIV-seronegative (HIV-) controls. Efforts were made to match the groups on the basis of chronological age, race, and hemophilia severity. The baseline evaluation included blinded neuropsychologic measurement of motor, attention, language, visual processing, memory, and general intelligence. HIV+ and HIV-group means did not differ at baseline on any neuropsychologic domain, and this trend continued at the 2-year follow-up. Mixed models analyses did not indicate that the HIV+ group performed more poorly than the HIV- group on any of the neuropsychological domains, nor did they show different patterns of change over time on these variables for the HIV+ group. Consistent with emergent findings, it continues to be premature to attribute subtle neuropsychologic deficits in seropositive children with hemophilia directly to the central nervous system (CNS) effects of HIV infection.
OBJECTIVE:To examine factors associated with perinatal HIV-1 transmission among twins.METHODS:We identified twins delivered by a population-based cohort of HIV-infected mothers on New York State Medicaid. Tested algorithms were applied to Medicaid files to identify HIV infection in mothers and twins. The HIV transmission rate 3 years after delivery was assessed from Kaplan-Meier curves. Proportional hazards models with adjustment for twin clustering were used to determine the relative hazard (RH) of transmission.RESULTS:In 35 twin pairs, transmission was 20.5%. The risk of transmission was increased significantly for advanced maternal HIV infection (rh = 10.8, 95% confidence interval 2.11, 54.9). We found no association of birth order with twin HIV status.CONCLUSIONS:These data suggest that maternal stage of disease plays a greater role in vertical HIV transmission than birth order. To prevent maternal-child HIV transmission, reducing maternal viral load is likely to have a greater impact than modifying delivery factors.
Although biologic and environmental risk factors show an age-dependent effect on children's cognitive development, outcome studies have yet to consider the role such factors play in the development of children born to HIV-1-infected women. This study explored the age-dependent differential impact of such risk factors on the cognitive functioning of children exposed in utero to HIV-1. Eighty-two children were administered a standardized measure of cognitive functioning and divided into two groups depending on their age when tested. Group 1 included children age 2 to 29 months (n = 46); Group 2 included children age 30 to 101 months (n = 36). Correlations between cognitive test scores and specific risk factors revealed an age-related double-dissociation. Serostatus and percent of CD4 cells correlated moderately with cognitive test scores in Group 1; however, these correlations were attenuated and nonsignificant in Group 2. Conversely, caregiver status and cognitive test scores were uncorrelated in Group 1, but were correlated in Group 2. These findings support a risk and resilience model of development. That is, in the context of biologic risk factors, aspects of the child's environment may either facilitate or hinder cognitive development.
Objective: To review the impact of routine followup cranial computed tomography (CT) scans on the management of children with human immunodeficiency virus (HIV) infection.Design: Longitudinal data collected from 58 HIV-infected children followed in one center for mean of 3.8 +/- 1.8 years. Setting: HIV/AIDS pediatric program following over 90% of the identified HIV-infected children in one region in Canada.Results: The baseline CT scans showed intracranial abnormalities in 35 of 58 children (60%). In five children with basal ganglia calcifications (BGC) without cerebral atrophy, there has not been progressive encephalopathy. For the 43 children who had serial CT scans for routine follow-up, 34 (79%) had changes in the scans that were concordant with the clinical assessment. In all but five children with progressive ventricular and sulcal dilatation on CT scan, there was simultaneous clinical evidence of encephalopathy. Those five children were already on antiretroviral therapy, and therapy was not changed in response to the CT scan findings.Conclusion: Baseline CT scans provide useful diagnostic and prognostic information. Further research is needed to evaluate the role of cranial CT imaging in the management of pediatric HIV encephalopathy.
Due to the increased risk of human immunodeficiency virus (HIV) infection during the childbearing years, voluntary screening during the prenatal period has been suggested. To study the impact of such a program in our population of pregnant women, we offered HIV testing to all prenatal patients with informed consent, beginning January 1, 1992. After 18 months (July 1993), HIV testing was offered as a component of our prenatal laboratory panel, using informed refusal. During the first screening period, there were 20 seropositive women among the 14,143 patients (1.4/1000), with 74 refusing testing. During the next 36 months (July 1993 to June 1996), 91 seropositive gravidas were identified among 31,496 parturients (2.9/1000), with only 17 refusing assessment. Free treatment with zidovudine (AZT) for both mother and baby, sponsored by the Mississippi state health department, began in January 1994. The perinatal transmission rate was 33% before AZT treatment, during our period of assessment, and was reduced to 10% during the next 30 months. Based on our data, it appears that a program of universal voluntary screening for HIV infection using informed refusal and free AZT for patients at risk for perinatal transmission results in almost 100% testing and a reduction in vertical transmission.
Objective: This article, the third in a 3-part series, describes recommendations for the reporting of cost-effective analyses (CEAs) intended to improve the quality and accessibility of CEA reports.Participants: The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, convened by the US Public Health Service.Evidence: The panel reviewed the theoretical foundations of CEA, current practices, alternative methods, published critiques of CEAs, and criticisms of general CEA methods and reporting practices.Consensus Process: The panel developed recommendations through 2 1/2 years of discussions. Comments on preliminary drafts were solicited from federal government methodologists, health agency officials, and academic methodologists.Conclusions: These recommendations are proposed to enhance the transparency of study methods, assist analysts in providing complete information, and facilitate the presentation of comparable cost-effectiveness results across studies. Adherence to reporting conventions and attention to providing information required to understand and interpret study results will improve the relevance and accessibility of CEAs.
UNLABELLED A number of clinical and laboratory features of human immunodeficiency virus (HIV) infection are found in systemic lupus erythematosus (SLE). OBJECTIVE To analyze the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP) in both diseases. METHODS We studied sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE, and from 50 healthy children. Anti-snRNP antibodies were detected by (ELISA) using recombinant and affinity-purified nuclear antigens, by counterimmunoelectrophoresis (CIE), and by immunoblotting using extractable nuclear antigens. RESULTS Anti-snRNP antibodies were detected by ELISA in 30 HIV-infected patients (68.1%) and 19 SLE patients (86.3%). These antibodies were directed against U1-RNP (61.3% and 77.2%), Sm (29.5% and 54.5%), 60kD-Ro/SS-A (47.7% and 50%), and La/SS-B proteins (18.1% and 9%), respectively. None of the HIV-infected children and 11 SLE patients (50%) showed anti-snRNP antibodies by CIE. None of the HIV-infected patients showed anti-70 kD U1-RNP or anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted relative to the presence of nonprecipitating anti-snRNP antibodies. No such reactivities were observed among the normal sera tested. CONCLUSIONS Nonprecipitating anti-snRNP antibodies in HIV-infected children are as frequent as in childhood-onset SLE. The significance of these antibodies is not clear at present. Perhaps they are polyreactive and low-affinity antibodies and a mechanism of molecular mimicry may explain these results; however, we cannot exclude a specific stimulation of B-cells by nuclear antigens.
