Search PubMed⌕ Search

Biomedical subjects

R E McKinney

Publications and source records attributed to R E McKinney.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evaluation of surrogate markers and clinical outcomes in two-year follow-up of eighty-six human immunodeficiency virus-infected pediatric patients.

OBJECTIVES: To evaluate the prognostic value of surrogate markers (HIV RNA copy number, CD4 counts and CDC clinical and immunologic categories) in HIV-infected children through a 2-year period. METHODS: Eighty-six HIV-infected children followed by the Duke Pediatric HIV Clinic in the fall of 1994 were evaluated for plasma HIV RNA concentration (viral load), CD4 lymphocyte percentage, age, antiretroviral treatment status and CDC clinical and immunologic categories. Follow-up evaluations were performed for approximately 2 years, and the time to progression to a new CDC category C diagnosis or death was noted. RESULTS: Of 86 children 22 had progression to new Category C diagnosis or death. Seven children died, 17 had a new Category C diagnosis and 2 had both. Among children who progressed, the median CD4 percentage at entry was 3% (absolute count, 75 cells/mm3), whereas children who had no disease progression entered with a median of 29% (868 cells/mm3). The overall median viral load at study entry was 4.58 log10 copies/ml (38,019 copies/ml, with a range of 1.7 to 6.78 logs). Children who had no disease progression had a median log copy number of 4.43, whereas 5.18 was the median for children whose disease progressed. Log copy number declined over time in children < 3 years of age, whereas it remained fairly consistent for children 3 years or older. Progression rates were determined by entry plasma HIV RNA concentration quartiles [quartile boundaries < 4.18, 4.58, > 5.08 log RNA copy/ml (< 15,136, 38,019 and > 120,226 copies/ml, respectively)]. Progression rates by quartile were 0 of 21, 4 of 22, 5 of 21 and 13 of 22. Kaplan-Meier survival curves defined by CD4% less than or greater than 15 and log RNA less than or greater than 5.0 (100,000) revealed that patients with CD4% less than 15 and plasma HIV RNA concentration > 5 log10 copies/ml did least well: 11 of 12 (92%) had a progression event at a median of 179 days. Patients with a high CD4 percentage and high viral load, or a low CD4 percentage and low viral load did similarly; 5 of 14 (36%) and 4 of 12 (33%) had progression events, respectively. Patients with high CD4 percentage and low viral load did best: only 2 of 48 (4%) had a progression event. CONCLUSIONS: The two most significant prognostic indicators of disease progression were the initial CD4 percentage and the plasma HIV RNA concentration, and a combination of CD4 percentage and virus load best predicted which children had progression events. Progression was less common in children who had < 100,000 HIV RNA copies/ml initially (6 of 60 vs. 16 of 26; P < 0.001; relative risk 0.16). Therefore it seems reasonable that in a child for whom complete suppression is not possible, a threshold of 100,000 (5 log10 copies/ml) can be used to mandate a change in therapy.

Adolescent↗
PubMed1998

A randomized comparative trial of stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection. AIDS Clinical Trials Group 240 Team.

OBJECTIVES: To compare the safety and tolerance of stavudine (d4T) versus zidovudine (ZDV, AZT) in symptomatic human immunodeficiency virus-infected children 3 months to 6 years of age. METHODS: In an initially double-blind trial, 212 evaluable human immunodeficiency virus-infected children who had received no more than 6 weeks of previous antiretroviral therapy were randomized to receive either d4T (1 mg/kg orally every 12 hours, maximum 40 mg orally every 12 hours) or zidovudine (180 mg/m2 orally every 6 hours, maximum 200 mg orally every 6 hours). The study was unblinded after a median follow-up period of 6.3 months; median follow-up at study closure was 17.3 months. Tolerance, safety, disease progression, and immunologic responses were evaluated. RESULTS: The patient population was young (median age, 1.2 years; range, 0.3 to 6.4 years), with a median baseline CD4+ lymphocyte count of 965 cells/microL (range, 18 to 4238 cells/microL). Neutropenia < 400/microL occurred significantly more commonly among zidovudine recipients (1-year event rates of 20% both up to the time of unblinding and throughout the entire study) than among children receiving d4T (1-year event rates of 5% up to the time of unblinding and 6% throughout the entire study). In exploratory activity analyses using all data collected until study closure, children treated with d4T showed consistently greater positive changes from baseline in weight-for-age-and-gender z scores. As expected in this population of young children, median absolute CD4+ lymphocyte counts decreased in both treatment groups. Smaller changes from baseline were noted among d4T recipients. CONCLUSIONS: In children between the ages of 3 months and 6 years, d4T and zidovudine are largely comparable in terms of safety and tolerance. Neutropenia occurs significantly less commonly among children treated with d4T. There was evidence that weight gain and absolute CD4+ lymphocyte counts were better maintained in children receiving d4T.

Anti-HIV Agents↗
PubMed1997

Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team.

BACKGROUND: Zidovudine has been the drug of choice for the initial treatment of symptomatic children infected with the human immunodeficiency virus (HIV). This trial was designed to assess the efficacy and safety of treatment with zidovudine alone as compared with either didanosine alone or combination therapy with zidovudine plus didanosine. METHODS: In this multicenter, double-blind study, symptomatic HIV-infected children 3 months through 18 years of age were stratified according to age (<30 months or > or =30 months) and randomly assigned to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end point was length of time to death or to progression of HIV disease. RESULTS: Of the 831 children who could be evaluated, 92 percent had never received antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim analysis (median follow-up, 23 months) showed a significantly higher risk of HIV-disease progression or death in patients receiving zidovudine alone than in those receiving combination therapy (relative risk, 0.61; 95 percent confidence interval, 0.42 to 0.88; P=0.007). The study arm with zidovudine alone was stopped and unblinded; the other two treatment arms were continued. At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91). A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P=0.036). CONCLUSIONS: In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.

Adolescent↗
PubMed1997

Effect of influenza immunization on immunologic and virologic characteristics of pediatric patients infected with human immunodeficiency virus.

OBJECTIVES: We evaluated the responses of HIV-infected children to a single dose of split-virus influenza vaccine and the relationship to viral load and other characteristics. METHODS: Fifty-three HIV-infected children ages 1.8 to 13.2 years were given influenza vaccine for the 1994 to 1995 influenza season (Wyeth-Ayerst: A/Texas H1N1, A/Shangdong H3N2 and B/Panama). Immunologic and virologic factors were assessed at the time of and 2 to 10 weeks after immunization. RESULTS: The differences between pre- and postimmunization CD4+ counts, CD4+:CD8+ ratios and viral load were not significant. Thirty-one of 53 children (58.4%) had a > 2-fold increase and 16 of 53 (30%) had a 4-fold rise in their postimmunization antibody titers for at least one component of the vaccine. Influenza immunization in the 1993 to 1994 flu season and administration of intravenous immunoglobulin around the time of immunization was not associated with immune response to the vaccine. Factors that were negatively associated with antibody response included increased time between samples (P = 0.004) and decreased preimmunization CD4+:CD8+ ratio (P = 0.02). CONCLUSIONS: Influenza immunization in this population is safe, and a positive antibody response to influenza immunization is not associated with significant clinical events or change in HIV-1 plasma viral burden.

Adolescent↗
PubMed1996

Outcome measures of a chronic pain program: a prospective statistical study.

OBJECTIVE: To provide outcome data measuring objective and subjective variables of an individualized, multidisciplinary, comprehensive pain management program. DESIGN: The study is a prospective evaluation of 50 consecutive patients who completed the pain management program. Objective measures were medication use and return to work. Subjective measures included self-reports of pain levels and completion of a Personal Concerns and Goals Assessment (PCGA) examining issues of lifestyle and emotional well-being. These measures were compared at program onset and completion by using appropriate statistical analyses. RESULTS: Objective measures: Medication use by the study subjects decreased overall by 72% within all drug categories. Opioid use was eliminated. Regarding return to work, the study subjects increased their work hours by twofold overall. Of patients working fewer than 30 h per week at program onset, representing 62% of the study population, a fivefold return to work was observed. Subjective measures: Overall pain levels improved by 33%, with an 18 to 47% improvement in all descriptors (average pain levels on good or bad days, average number of good or bad days). Of the PCGA factors, patients improved 24 to 46% in all categories concerning lifestyle and emotional well-being. Correlative analysis of the data produced prognostic information as well as insights into chronic pain development. CONCLUSIONS: This study of objective and subjective outcome measures demonstrates that a comprehensive program employing specific principles and methods produces an effective approach for the management of chronic pain. Patients disabled by chronic pain regain a quality of life that allows them to resume a functioning, productive role.

Adolescent↗
PubMed1996

Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children. AIDS Clinical Trials Group Protocol 152 Study Team.

BACKGROUND: A large cohort of antiretroviral therapy-naive, symptomatic, HIV-infected children were enrolled into a controlled therapeutic trial (AIDS Clinical Trials Group Protocol 152), providing an opportunity to describe their clinical and laboratory characteristics and determine age-related distinctions. METHODS: Study entry evaluations for 838 of 839 enrolled children were analyzed. Weight, head circumference (if < 30 months of age), neuroradiologic imaging of the head, developmental or cognitive status and neurologic examination were assessed. Laboratory studies included hemoglobin, absolute neutrophil count, CD4 cell count, serum amylase, alanine aminotransaminase, p24 antigen and HIV blood culture. Data were categorized by age (3 to < 12 months, 12 to < 30 months, 30 months to 6 years and > or = 6 years). RESULTS: Younger children had significantly higher rates of abnormalities before antiretroviral therapy, especially factors relating to growth and neurologic or cognitive function. Lower CD4+ cell counts and percentages as well as a positive serum p24 antigen correlated with lower weight-for-age Z scores and developmental indices. CONCLUSIONS: These data provide a description of the clinical characteristics of HIV-infected US children at the time antiretroviral therapy is initiated for HIV-related symptoms. The high rate of abnormalities of growth, development and cognitive ability that were observed in children < 30 months of age demonstrates that treatment strategies should be developed for earlier intervention.

AIDS-Related Opportunistic Infections↗
PubMed1996

Antiretroviral therapy: evaluating the new era in HIV treatment.

Tools for evaluating antiretroviral therapy are still evolving. Key components are available such as the laboratory assays themselves, but results from these assays are being analyzed and presented inconsistently, making interstudy comparisons difficult or impossible. In part, the problems in analysis and presentation reflect a lack of completed clinical trials in which new laboratory methods such as RNA copy numbers can be validated. Survival is the clearest valid end point in clinical trials of antiretroviral drugs. Beyond life and death, the next most important issue is quality of life. Because of the difficulty in agreeing what "quality of life" means, and the even greater problems measuring such an abstract concept, in most cases assessments are made of more quantifiable clinical elements: cognitive and motor function, growth, and the frequency of opportunistic infections. Laboratory markers of disease progression are very quantifiable but have meaning only when they predict clinical outcome. There is a consensus that CD4+ counts, CD4+ percentages, and HIV copy numbers measured by RNA PCR are important. There is not, however, a consensus approach to interpretation of data from any of these markers of HIV disease, particularly because the interpretation may vary based on the patient's level of clinical disease. With time and more clinical trials with which to clarify their use, these tools should become more uniformly applied, at which point cross-study comparisons might be possible. Progress is already being made in the development of new antiretroviral therapies, and with improved evaluation techniques the evolution of new anti-HIV treatments should become an even more efficient process.

Adolescent↗
PubMed1994

Growth as a prognostic indicator in children with human immunodeficiency virus infection treated with zidovudine. AIDS Clinical Trials Group Protocol 043 Study Group.

OBJECTIVE: To assess measures of growth as prognostic indicators in response to zidovudine treatment in children with symptomatic human immunodeficiency virus infection. METHODS: We retrospectively assessed data from AIDS Clinical Trials Group Protocol 043, an open-label, phase II study of oral zidovudine therapy (180 mg/m2 per dose every 6 hours) in children with human immunodeficiency virus who have severe symptoms. Several variables were evaluated for their prognostic significance: CD4+ lymphocyte percentage; rates of weight gain and linear growth; entry weight, height, and weight-for-height z scores for age; race; gender; age; and route of transmission. RESULTS: The overall survival rate as of April 1, 1992 (4 years after study initiation), was 44%, with a median survival of 37.9 months. The risk of death was greatest in children with CD4+ lymphocyte percentages < 20% (relative risk, 3.49), but was also increased in children who had a weight-for-age z score < -2 on entry to the study (relative risk, 1.53) and in those who failed to gain weight at the 25th percentile rate or greater during the first 6 months of therapy (relative risk, 2.03). These three factors, as well as race and gender, were found to be significant predictors in a multivariate, proportional-hazards model of survival. Entry height-for-age and height growth rates did not have predictive value for survival in univariate or multivariate analyses. CONCLUSIONS: Weight-for-age and rate of weight gain are important, easily obtained, and inexpensive prognostic indicators in children with symptomatic human immunodeficiency virus treated with zidovudine. Both were less predictive of survival than the entry CD4+ lymphocyte percentage.

Adolescent↗
PubMed1993

Pediatric acquired immunodeficiency syndrome. Barriers to recognizing the role of child sexual abuse.

The only reportable exposure categories for human immunodeficiency virus (HIV) infection of children are vertical transmission from an HIV-infected mother or receipt of infected blood or blood products. Although sexual transmission of HIV among adults is the subject of intense concern, sexual transmission of HIV to children during child sexual abuse has received almost no investigative attention. This review discusses factors contributing to the exclusion of sexual transmission of HIV to children from studies of the epidemiology of HIV infection. Difficulties occur in screening and confirming abuse in nonselected populations of children, perceived and real barriers exist to the evaluation for HIV of sexually abused children, and problems occur in the assessment for child sexual abuse of HIV-infected children. Impediments to the understanding of the relationship between sexual abuse and HIV infection in sexually abused, HIV-infected children are considered, and measures that can allow these barriers to be overcome are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Effect of human immunodeficiency virus infection on the growth of young children. Duke Pediatric AIDS Clinical Trials Unit.

We retrospectively analyzed the growth of 170 children less than 25 1/2 months of age who were referred for evaluation of human immunodeficiency virus (HIV) antibody status. By the age of 4 months, the 62 HIV-infected children were significantly smaller than the 108 uninfected children in both weight-for-age and length-for-age measurements; linear growth and weight gain were proportionally decreased.

Acquired Immunodeficiency Syndrome↗
PubMed1992

HIV-1 sensitivity to zidovudine and clinical outcome in children.

In adults with the acquired immunodeficiency syndrome, long-term monotherapy with zidovudine selects for human immunodeficiency virus type 1 (HIV-1) strains with substantially reduced in-vitro susceptibility to the drug. We have assessed the relation between in-vitro resistance to zidovudine and clinical outcome in children, in whom disease progression is more rapid than in adults. We studied 23 children with symptoms of HIV-1 disease during extended monotherapy with zidovudine. An in-vitro assay was used to determine the concentration of zidovudine required to inhibit by 50% the replication of viral isolates (IC50) obtained after 9 to 39 months of treatment. Viral stocks of high enough titre to yield reproducible results were obtained from 19 of the children. During the following 6 months of therapy, 9 children were stable, 7 deteriorated, and 3 died. There was a highly significant relation between decreased zidovudine susceptibility and poor clinical outcome (p less than 0.001) but no relation between IC50 and age at start of therapy or length of time on treatment. Age-adjusted CD4 lymphocyte counts were lower at the start of treatment (p = 0.02) and at the time of sampling (p = 0.01) in children whose viral isolates had an increased zidovudine IC50. Initial serum p24 antigen levels were not predictive of subsequent emergence of resistant virus, but at the time of sampling for viral sensitivity higher p24 antigen levels were associated with raised IC50 (p = 0.004). The findings suggest that most children who become unresponsive to monotherapy with zidovudine, as judged by clinical criteria, will have changes in in-vitro sensitivity to the drug. In these children, an alternative antiretroviral therapy should be considered.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Sexual abuse of human immunodeficiency virus-positive children. Outcomes for perpetrators and evaluation of other household children.

OBJECTIVE: To obtain the following data that pertain to programs for the prevention of sexual abuse and sexual transmission of human immunodeficiency virus (HIV) to children: (1) to determine the prevalence of sexual abuse among siblings and other children cohabiting with sexually abused HIV-positive children, and (2) to determine if programs designed to restrain identified perpetrators from further acts of child sexual abuse were instituted. DESIGN: Case series. SETTING: Households of previously described sexually abused HIV-infected children. PATIENTS AND OTHER PARTICIPANTS: Twenty-two siblings or other children who lived in the homes of 14 previously described HIV-infected sexually abused children. Eight perpetrators of the abuse were identified. MAIN OUTCOME MEASURES: Sexual abuse of cohabiting children was confirmed with disclosure interviews, witness by other persons, diagnosis of another sexually transmitted disease, or an abnormal physical examination result that was highly suggestive of sexual abuse. Telephone contact with the Department of Social Services, county sheriff or police, and district attorney provided data regarding reports, criminal indictments, trials, convictions, and plea-bargain arrangements for the identified perpetrators. RESULTS: Eleven (50%) of the 22 cohabiting children were confirmed to have been sexually abused and four (18%) were suspected of having been sexually abused. Seven (32%) of the cohabiting children could not be examined and it was not known if they had been sexually abused. No assailant was tried for a criminal offense, required to participate in offender therapy, or prohibited from unsupervised visitation of children. CONCLUSION: Programs for the prevention of sexual abuse and sexual transmission of HIV to children require means of ensuring the safety of children exposed to perpetrators and require adequate supervision of perpetrators and their adherence to therapy.

Academic Medical Centers↗
PubMed1992

Lymphocyte subsets in children younger than 2 years old: normal values in a population at risk for human immunodeficiency virus infection and diagnostic and prognostic application to infected children.

Data were collected prospectively from 116 children younger than 2 years old who were seen at the Duke Pediatric AIDS Clinical Trials Unit for known human immunodeficiency virus seropositivity. Forty-six (40%) of these children were human immunodeficiency virus-infected and 70 were not infected. Using 3-month blocks, 10th, 50th and 90th percentiles were calculated for the CD4+ and CD8+ cell counts, percentage of lymphocytes positive for CD4 and CD8 and T4:T8 ratios. Results from the infected and uninfected children were compared. By 3 to 6 months of age the infected patients had significantly lower CD4+ counts, percentage CD4+ cells and T4:T8 ratios, whereas the percentage of CD8+ lymphocytes was significantly higher. Absolute CD8+ counts were approximately the same in infected and uninfected children through age 2 years. Most infected children had one or more abnormal lymphocyte subset results (less than the 10th percentile for uninfected patients) by age 2: 83% had an abnormal CD4+ percentage; 78% had an abnormal T4:T8 ratio; and 67% had an abnormal CD4+ count. All 13 children who had an opportunistic infection (at any age) had an abnormal CD4+ percentage before age 2 years, and 12 of 13 had a low absolute CD4+ count or T4:T8 ratio. Among patients who died 10 of 11 had 1 or more low CD4+ count, 9 of 11 had an abnormal CD4+ percentage and 8 of 11 an abnormal T4/T8 ratio.

CD4-CD8 Ratio↗
PubMed1992

The introduction of human immunodeficiency virus into the North Carolina pediatric population.

The authors reviewed the means by which human immunodeficiency virus (HIV) seropositivity was acquired for the 134 seropositive children seen at Duke University Medical Center prior to September 1990. Perinatal transmission occurred in 111 (83%) and blood product transmission in 15 (11%). Of the 108 mothers (there were three sets of siblings) responsible for perinatal transmission, 44 (41%) had acquired their infection while residing in North Carolina. Intravenous (IV) drug use by the mother or her sexual partner was the significant risk factor for maternal infection in 91 (84%) of the total cases and in 38 (86%) of the 44 women infected in North Carolina. The proportion of women who acquired their HIV infection from a sexual partner who was an IV drug user was significantly greater for mothers who were resident in North Carolina when infected compared with mothers infected elsewhere (P less than .001). On the basis of admission to drug treatment programs during the 1990 fiscal year, cocaine is the predominant IV drug used in North Carolina. Admissions to cocaine abuse programs occurred throughout the state, and mothers who acquired HIV infection from IV drug use were more likely to live in counties with a higher frequency of cocaine abuse treatment.

Child↗
PubMed1991

A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group.

BACKGROUND AND METHODS: Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. RESULTS: Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent)--anemia (hemoglobin level, less than 75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, less than 0.75 x 10(9) per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children less than 3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263 x 10(9) per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. CONCLUSIONS: Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Human immunodeficiency virus transmission by child sexual abuse.

During 1987-1989, 14 (14.6%) of the 96 children who tested positive for the human immunodeficiency virus (HIV) and were followed up by the Duke University (Durham, NC) pediatric acquired immunodeficiency syndrome team were confirmed to have been sexually abused. Every sexually abused child was evaluated for each of five modes of HIV transmission, and in nine children the pathway was identified. Four of the study children acquired HIV from child sexual abuse and in six, abuse was a possible source. Transmission by child sexual abuse was the most frequent of the proven modes of acquisition of HIV in this population. The other proven modes of acquisition were vertical transmission (n = 3) and HIV-contaminated blood transfusion (n = 2). Twelve males were identified (n = 8) or suspected (n = 4) of being perpetrators. Three knew themselves to have HIV at the time of an assault and eight were aware that the child had HIV at the time of an assault. There was no indication from any child that "safe sex" precautions had been observed. Children with HIV infection had multiple risk factors for abuse or neglect. The sociological descriptors of the lives of the 14 abused children showed multiple known risk factors for sexual abuse that also overlapped with known risk factors for or sequelae of the acquisition of HIV infection. These included drug abuse and alcoholism in the home, prostitution of a parent, lack of parenting, poverty, and chronic illness of the child. Prevention efforts should recognize that children as well as adults are at risk for sexually transmitted HIV infection.

Adolescent↗