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Biomedical subjects

A Willoughby

Publications and source records attributed to A Willoughby.

At least 19 recordsLinked to original sources
PubMed1998

Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1998

The influence of pregnancy on human immunodeficiency virus type 1 infection: antepartum and postpartum changes in human immunodeficiency virus type 1 viral load.

OBJECTIVE: Our objective was to examine the influence of pregnancy on human immunodeficiency virus type 1 viral load by measuring human immunodeficiency virus type 1 ribonucleic acid levels during pregnancy and post partum. STUDY DESIGN: One or more plasma or serum specimens obtained before and during the third trimester, and at 2, 12, and 24 months post partum were available for 160 human immunodeficiency virus type 1-seropositive women enrolled in the Mothers and Infants Cohort Study between January 1986 and January 1991. All specimens were frozen and stored at -70 degrees C until analyzed in batch for human immunodeficiency virus type 1 ribonucleic acid by polymerase chain reaction. A multivariate longitudinal random effects model was developed to examine changes in human immunodeficiency virus type 1 ribonucleic acid levels over time. RESULTS: Overall, human immunodeficiency virus type 1 ribonucleic acid levels rose significantly during the study period, particularly during the second year post partum (mean, 0.09 log per year; 95% confidence interval, 0.03 to 0.15 logs per year; p = 0.005). However, the mean slope during pregnancy was not significantly different from zero (p = 0.65). CONCLUSION: Pregnancy had little immediate effect on human immunodeficiency virus type 1 viral load in most human immunodeficiency virus type 1-seropositive women.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Influence of other maternal variables on the relationship between maternal virus load and mother-to-infant transmission of human immunodeficiency virus type 1.

To assess the relationship between maternal human immunodeficiency virus (HIV) type 1 RNA level, other important covariates, and mother-to-infant (vertical) transmission of HIV-1, third trimester repository specimens from 160 HIV-1-seropositive women enrolled in the Mothers and Infants Cohort Study between 1986 and 1991 were assayed in batch for HIV-1 RNA. A significant association between peripheral blood HIV-1 RNA level and vertical transmission remained after controlling for CD4 cell level, duration of ruptured membranes, "hard" drug (cocaine and heroin) use, and frequency of sexual activity during pregnancy. However, the association was attenuated among women with advanced HIV infection and those with a high frequency of sexual activity during pregnancy. In these settings, interventions that target risk factors other than virus load may be particularly important for preventing vertical transmission of HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The future of prenatal HIV testing.

The use of zidovudine for the prevention of mother-to-child transmission of human immunodeficiency virus, as well as continuing advances in our understanding of the determinants of that transmission, and of potential new avenues of intervention augur ever more efficient perinatal prevention strategies in the near future. In this paper the evolving role of prenatal testing in an era of ever more successful interventions will be discussed. At least four factors will be critical in determining what that role will be: clinical, legal, ethical and economic. Each of these are parochial, i.e. they will feature in eradication strategies in different ways in different geographical, economic and cultural settings. An understanding of these factors will help to suggest what course testing policy should take and to determine the role clinicians must play if any testing policy is to succeed in contributing to the end of pediatric HIV disease.

AIDS Serodiagnosis↗
PubMed1996

Neurologic status of human immunodeficiency virus 1-infected infants and their controls: a prospective study from birth to 2 years. Mothers and Infants Cohort Study.

OBJECTIVE: To determine the timing, extent, severity, and persistence of neurologic abnormalities in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection compared with similar uninfected children of HIV-1-infected women and control children. METHODS: Serial neurologic examinations and head circumference measurements were performed on a cohort of HIV-1-infected children born to HIV-1-infected women, seroreverting children born to HIV-1-infected women, and control children born to uninfected women. Examination data from 32 HIV-1-infected children, 99 reverters, and 116 control children were summarized by eight neurologic domains. Data were analyzed by longitudinal analysis. RESULTS: Reverter children were not different from control children in neurologic function for any of the eight domains or head circumference. HIV-1-infected children had significantly more neurologic problems than the control and reverter children for seven of the eight domains. The HIV-1-infected children were further classified by whether they had acquired immunodeficiency syndrome (AIDS)-defining clinical conditions (other than lymphoid interstitial pneumonitis) in the first 24 months of life (the AIDS-opportunistic infection group) or did not (the infected-other group). Neurologic abnormalities were early, severe, pervasive, and persistent in the AIDS-opportunistic infection group, and nearly all in this group had head circumference measurements below the 10th percentile. The infected-other group had no statistically significant differences from the uninfected children, although individual children in the infected-other group had some abnormalities. CONCLUSIONS: In utero exposure to HIV-1 without infection seems to have no negative impact on neurologic function in children in the first 2 years of life. Among children with perinatally acquired HIV-1 infection, the most severe and pervasive neurologic problems occur in those children who have early serious HIV-1 clinical disease. Most children without serious AIDS-defining clinical conditions in the first 2 years of life are also free from serious neurologic problems during that period.

AIDS-Related Opportunistic Infections↗
PubMed1995

Polyarthritis in the rat: effects of tolerance and sensitization to the bacterial extract OM-89 with a possible mode of action.

The Bacterial Extract OM-89 has been shown to significantly reduce paw swelling in an avridine-induced polyarthritis (AvPA) in female Wistar rats whether given orally for 3 weeks or as a series of i.p. injections. Paw swelling was also markedly reduced in groups of adult rats which had received i.p. injections of OM-89 as neonates. Three separate tolerance-inducing regimes were used and all were equally effective. It is suggested that OM-89 can modulate the undesirable immunological reactions to endogenous antigens and since oral administration has been shown to be clinically effective in the human, that the induction of oral tolerance could be a mechanism of action of OM-89.

Adjuvants, Immunologic↗
PubMed1994

Maternal and pediatric AIDS in the United States: the current situation and future research directions.

The epidemic of HIV infection and disease in women, adolescents and children represents a complexly intertwined biological and social challenge to health care workers and researchers alike. When considering various issues in confronting this epidemic, women must be viewed as individuals important in their own right, as the primary caretaker of their family members (both infected and uninfected), and as the sexual partners of men who may or may not be infected. Of the myriad of compelling biological questions facing AIDS researchers today, two of the most interesting involve the timing and determinants of vertical transmission and the natural history of HIV infection and disease in women. Scientifically, confronting this epidemic involves research into pathogenesis, epidemiology, natural history, treatment, and prevention of HIV infection. Primary emphasis in the research arena in HIV/AIDS in the United States is focused on therapeutic and prophylactic research. Other research issues are very important, including studies of early diagnostic techniques, behavioral research concerning reproductive choices, the role of breastfeeding in HIV transmission, HIV-specific adolescent issues, and surrogate markers of disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Immunoglobulin class and subclass antibodies to HIV proteins in maternal serum: association with perinatal transmission.

A flow cytometry-based assay for detection of immunoglobulin (Ig) class and subclass antibodies in human serum or plasma was developed. With use of this procedure, the presence and relative frequency of antibody activity in the Ig classes and subclasses (IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, and IgM) to human immunodeficiency virus type 1 (HIV-1) proteins (gp160, gp120, p66, and p24) was determined in serum or plasma from a cohort of 47 HIV-1-infected, pregnant women. Antibody activity in each of the classes and subclasses was found with differences in frequency depending on the Ig class/subclass and the HIV-1 protein. IgG1 antibodies were the most frequently reactive Ig class/subclass to each protein. Intermediate frequencies of reactivity were found in IgA1, IgG2, IgG3, and IgM class and subclasses and antibodies of the IgA2, IgE, and IgG4 class/subclass the least frequently detected. An unexpected finding was the presence of IgD antibodies to HIV-1 proteins in approximately 50% of the individuals. The distributions of Ig class/subclass antibodies to the different HIV-1 proteins were compared in sera from 14 mothers giving birth to infants who were determined to be HIV-1 infected with sera from 25 individuals whose infants were not infected. Sera from transmitting mothers contained a broader distribution of class and subclass antibodies compared to sera from nontransmitting women. The single most frequent antibody-antigen combination that was found in the transmitting mother was IgG2-gp160.(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies↗
PubMed1994

A nonparametric analysis of the transmission rate of human immunodeficiency virus from mother to infant.

Infants born to mothers who are infected with the human immunodeficiency virus (HIV) may or may not become infected by perinatal transmission. Unfortunately, passively transferred maternal antibodies make it hard to determine the infant's infection status from HIV antibody testing, because shortly after birth it is not possible to distinguish passively transferred maternal antibodies from antibodies produced by an infected infant. Usually, the infection status is unobservable for each infant, unless the infant reaches the age of 15 months or develops an HIV-related disease such as the acquired immunodeficiency syndrome (AIDS). Traditionally, statistical analyses of the perinatal transmission rate of HIV are based on infants who had been born at least 15 months before the date of analysis. Such analyses can be both inefficient and biased. In this note, we define a mixture model underlying the onset time of AIDS and then obtain the nonparametric maximum likelihood estimators of the HIV transmission rate and of the distribution function of AIDS onset time for infected infants. Nonparametric tests are also derived for detecting differences in HIV transmission rates among different groups of infants. Finally, the methods are applied to the Mothers and Infants Cohort Study in New York City. The transmission rate of HIV from infected mothers to their infants was estimated to be 30.0% with 95% confidence interval (22.3%, 39.1%).

Age of Onset↗
PubMed1994

Cigarette smoking, premature rupture of membranes, and vertical transmission of HIV-1 among women with low CD4+ levels.

To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4+ level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0-31.3). Prenatal CD4+ lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4+ level was < 20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46-7.44; p = 0.004]. Among mothers who developed premature rupture of membranes, those with a low CD4+ level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78-10.5; p = 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48-2.70; p = 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61-2.74; p = 0.50), indicating that these factors modified the effect of CD4+ level on transmission. Among all mothers without regard to CD4+ level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07-4.69; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of perinatally acquired human immunodeficiency virus infection on neurodevelopment in children during the first two years of life.

OBJECTIVE: To determine the timing, extent, and magnitude of neurodevelopmental problems in children with perinatal HIV infection compared to similar uninfected children of HIV-infected women and controls. METHODS: Neurodevelopmental assessments during the first 24 months of life for 21 HIV-infected children born to HIV-infected mothers, 65 seroreverted children born to HIV-infected mothers, and 95 non-HIV-infected children born to non-HIV-infected mothers were analyzed. Neurodevelopment was assessed by using the Bayley Scales of Infant Development beginning at 3 months of age. Kent Scoring Adaptation was also utilized. A two-stage Hierarchical Linear Model was used for analysis of neurodevelopmental scores. RESULTS: In the initial comparison of these three groups, infected children had significantly lower scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) than the other two groups. The HIV-infected children were further classified into HIV-infected without Centers for Disease Control-defined AIDS, those with lymphoid interstitial pneumonitis (LIP) only as their AIDS-defining illness, and children with an AIDS-defining diagnosis other than LIP in the first 24 months. The children with LIP-only AIDS and the infected children without AIDS on average were not significantly different from the seroreverters or the controls on MDI or PDI, while the children with non-LIP AIDS had significantly lower scores after 3 months of age. Analysis of the Kent scores indicated that the decrement in the non-LIP AIDS children was seen in all five functional domains. CONCLUSION: Children with serious HIV symptomatology appear to be at very high risk for serious developmental impairments, HIV-infected children not highly symptomatic have relatively normal neurodevelopment, and uninfected children of HIV-infected mothers do not appear to be adversely affected by the mother's HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Hemophilia growth and development study. Design, methods, and entry data.

PURPOSE: The study design, research questions, and baseline data are presented from a multicenter longitudinal epidemiologic investigation of the impact of human immunodeficiency virus (HIV) infection on three areas of functioning in children and adolescents with hemophilia: physical growth and sexual maturation, immune function, and neurological and neuropsychological functioning. PATIENTS AND METHODS: Sixty-nine percent (n = 333) of a population of males between the ages of 6 and 19 years with moderate to severe hemophilia participated in a comprehensive baseline examination. Approximately 62% of the study group was HIV seropositive and 38% HIV seronegative. RESULTS: Adjusted for age, HIV-positive participants were three times as likely as HIV-negative participants to exhibit declines in height-for-age attainment (p = 0.05), twice as likely to have delays in sexual maturation (p = 0.414), and more than three times as likely to exhibit antibody levels that were not indicative of prior exposure or vaccination (p < 0.001). In addition, analysis of a comprehensive battery of neuropsychological tests showed that HIV-positive participants were 50% more likely to show scores approximately 1 SD below expected levels in three of nine functional areas (p = NS) compared with HIV-negative participants. CONCLUSIONS: Entry data for this study reveal a greater likelihood for HIV-positive children and adolescents with moderate to severe hemophilia to have abnormal growth, and to exhibit antibody levels not indicative of prior exposure to disease or vaccination, which could be attributed to HIV infection. Lowered neuropsychological test performance in both groups may be attributable to the deleterious effects of chronic illness. Data are being collected from a group of non-HIV infected non-hemophiliac siblings for comparison.

Adolescent↗
PubMed1992

Vertical transmission of human immunodeficiency virus (HIV) infection. Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1.

The observation that approximately 70% of HIV-infected pregnant women do not transmit infection vertically suggests that antibody therapy may be effective in the prevention of transmission of HIV infection from mother to child. Currently, there is an incomplete understanding of the processes involved in vertical transmission of HIV infection. The elucidation of the serological basis of maternal immunity as it relates to protection from vertical transmission is the goal of this study. We have screened 20 maternal sera from HIV+ individuals of known vertical transmission status for reactivity with 31 peptides spanning the entire envelope glycoprotein of HIV-1. Of interest was reactivity to regions outside of the V3 loop of gp120. The findings have been examined in relationship to transmission status, as well as to in vitro anti-HIV-1 biological activity. Our results indicate that lack of vertical transmission is correlated with high viral neutralization activity, but not with antisyncytial activity nor with binding to the V3 peptides examined in this study. Also, the transmission group bound to fewer gp41 peptides when compared with the nontransmission group, suggesting that immune responses to gp41 may be important in preventing transmission. These findings may provide insights into the design of passive immunotherapies.

Adult↗
PubMed1991

Clinical utility of HIV-IgA immunoblot assay in the early diagnosis of perinatal HIV infection.

OBJECTIVE: To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. DESIGN: Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. SETTING: Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. PATIENTS: Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. MAIN OUTCOME MEASURE: Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. RESULTS: The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%--no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. CONCLUSION: The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms.

Female↗