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J J Goedert

Publications and source records attributed to J J Goedert.

At least 91 records · Page 5Linked to original sources
PubMed1998

Use of neural networks to model complex immunogenetic associations of disease: human leukocyte antigen impact on the progression of human immunodeficiency virus infection.

Complex immunogenetic associations of disease involving a large number of gene products are difficult to evaluate with traditional statistical methods and may require complex modeling. The authors evaluated the performance of feed-forward backpropagation neural networks in predicting rapid progression to acquired immunodeficiency syndrome (AIDS) for patients with human immunodeficiency virus (HIV) infection on the basis of major histocompatibility complex variables. Networks were trained on data from patients from the Multicenter AIDS Cohort Study (n = 139) and then validated on patients from the DC Gay cohort (n = 102). The outcome of interest was rapid disease progression, defined as progression to AIDS in <6 years from seroconversion. Human leukocyte antigen (HLA) variables were selected as network inputs with multivariate regression and a previously described algorithm selecting markers with extreme point estimates for progression risk. Network performance was compared with that of logistic regression. Networks with 15 HLA inputs and a single hidden layer of five nodes achieved a sensitivity of 87.5% and specificity of 95.6% in the training set, vs. 77.0% and 76.9%, respectively, achieved by logistic regression. When validated on the DC Gay cohort, networks averaged a sensitivity of 59.1% and specificity of 74.3%, vs. 53.1% and 61.4%, respectively, for logistic regression. Neural networks offer further support to the notion that HIV disease progression may be dependent on complex interactions between different class I and class II alleles and transporters associated with antigen processing variants. The effect in the current models is of moderate magnitude, and more data as well as other host and pathogen variables may need to be considered to improve the performance of the models. Artificial intelligence methods may complement linear statistical methods for evaluating immunogenetic associations of disease.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Estimating the cumulative incidence of HIV infection among persons with haemophilia in the United States of America.

We used complementary approaches to estimate the cumulative incidence of infection with the human immunodeficiency virus (HIV) among persons with haemophilia in the United States of America. One approach, ratio estimation, divided the cumulative number of haemophiliacs diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States by the corresponding cumulative proportion with AIDS among HIV-positive subjects in the Multicenter Hemophilia Cohort Study (MHCS). The other approach, back-calculation, reconstructed past HIV incidence from national surveillance of AIDS using essentially non-parametric estimates of the hazard functions for AIDS and for pre-AIDS death. We derived confidence intervals that fully incorporated uncertainty about the hazard functions. Results from the two approaches were consistent. Around 9200 haemophiliacs became infected during the course of the epidemic. Of them, around 7000 were living with HIV or AIDS as of 31 December 1992 and at least 5630 as of 31 December 1995. Credible calculations for this group must account for those who die before AIDS and for the significantly longer incubation times in those infected as children or adolescents. The consistency of back-calculation and cohort data in haemophiliacs supports the use of back-calculation to estimate prevalence in other populations.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Contamination of poliovirus vaccines with simian virus 40 (1955-1963) and subsequent cancer rates.

CONTEXT: Poliovirus vaccine contaminated with live simian virus 40 (SV40), a macaque polyomavirus that is tumorigenic in rodents, was used extensively in the United States between 1955 and 1963. Simian virus 40 DNA has recently been detected in several rare human tumors, including ependymomas, osteosarcomas, and mesotheliomas. OBJECTIVE: To determine the risk of ependymoma, osteosarcoma, and mesothelioma among Americans who as children received SV40-contaminated poliovirus vaccine. DESIGN: Retrospective cohort study using data from the Surveillance, Epidemiology, and End Results program (1973-1993) and the Connecticut Tumor Registry (1950-1969), as well as national mortality statistics (1947-1973). SETTING: United States. PARTICIPANTS: Birth cohorts that were likely to have received SV40-contaminated poliovirus vaccine as infants, born 1956 through 1962 (60 811730 person-years of observation); as children, born 1947 through 1952 (46430953 person-years); or that were unexposed, born 1964 through 1969 (44959979 person-years). MAIN OUTCOME MEASURES: Relative risk (RR) of each cancer among exposed compared with unexposed birth cohorts. RESULTS: Age-specific cancer rates were generally low and were not significantly elevated in birth cohorts exposed to SV40-contaminated vaccine. Specifically, compared with the unexposed, the relative risk of ependymoma was not increased in the cohorts exposed as infants (RR, 1.06; 95% confidence interval [CI], 0.69-1.63), or as children (RR, 0.98; 95% CI, 0.57-1.69) nor did the exposed have an increased risk of all brain cancers. Osteosarcoma incidence also showed no relation to exposure as infants (RR, 0.87; 95% CI, 0.71-1.06) or children (RR, 0.85; 95% CI, 0.59-1.22). Last, mesotheliomas were not significantly associated with exposure, although the cohorts studied have not yet reached the age at which these tumors tend to occur. CONCLUSIONS: After more than 30 years of follow-up, exposure to SV40-contaminated poliovirus vaccine was not associated with significantly increased rates of ependymomas and other brain cancers, osteosarcomas, or mesotheliomas in the United States.

Adolescent↗
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↗
PubMed1998

Hepatitis C virus infection in the mothers and infants cohort study.

OBJECTIVES: To estimate the hepatitis C virus (HCV) vertical transmission rate, the effect of potential risk factors, and the pattern of HCV antibody response and viremia in HCV-infected infants. STUDY DESIGN: The Mothers and Infants Cohort Study enrolled both human immunodeficiency virus (HIV)-seropositive and HIV-seronegative pregnant women at five obstetric clinics in New York City in a prospective cohort study between January 1986 and January 1991. HCV-infected mothers and their 122 offspring were followed-up for a minimum of 12 months for evidence of HCV infection as determined by persistent HCV antibodies or detection of HCV RNA by reverse transcription polymerase chain reaction. Comparisons among groups for categorical variables were performed using the Fisher's exact test. RESULTS: Seven (6%; 95% confidence interval, 2%-11%) of the 122 infants were HCV-infected. There was a tendency for increased risk of transmission with maternal viral and obstetrical factors, such as coinfection with HIV (7% vs 4%), high HIV viral load (13% vs 6%), HCV viremia (8% vs 3%), vaginal delivery (6% vs 0%), and female gender of offspring (8% vs 3%), although none of the associations reached statistical significance. After loss of maternal antibody, HCV antibody seroconversion occurred at a mean age of 26 months in 3 HIV-coinfected infants compared with 7 months of age in 4 HCV-infected HIV-uninfected infants. Serial samples showed that HCV RNA persisted in 6 infants for at least 18 to 54 months. CONCLUSIONS: Our study is in accordance with other studies that have shown low overall HCV vertical transmission risk and a trend toward higher risk with maternal risk factors such as HIV-coinfection or HCV viremia. A delay in infant HCV antibody response may be associated with HIV coinfection although larger studies are needed to confirm these findings.

AIDS Serodiagnosis↗
PubMed1997

Survival after AIDS diagnosis in a cohort of hemophilia patients. Multicenter Hemophilia Cohort Study.

We studied factors affecting survival after the diagnosis of AIDS in a cohort of 1253 patients with hemophilia. The nature of the AIDS-defining condition was found to be as important as age at seroconversion and CD4+ lymphocyte level in predicting survival. A multivariate analysis yielded estimates of median survival for groups defined by age at seroconversion (0 through 15, 16 through 69), CD4+ lymphocyte count (<100 cells/microl versus > or = 100 cells/microl), and 10 AIDS-defining disease groups. Estimates of median survival after a single AIDS-defining condition ranged from 3 to 51 months, depending on the diseases. Median survival after a second AIDS-defining condition was about 1.5- to 2.0-fold shorter than after an initial, isolated AIDS-defining condition. HIV-related neurologic disease (i.e., AIDS dementia complex or multifocal leukoencephalopathy) was a notable exception. It correlated with the shortest estimates of median survival (3 to 9 months), and this poor prognosis was no worse for patients who had a second AIDS-defining condition. The results of this analysis were consistent in most respects with other published analyses of factors affecting survival. These findings may be useful in the clinical care of persons with AIDS and in estimating the number of persons alive who have had a particular AIDS-defining disease.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Sexual behavior and injection drug use during pregnancy and vertical transmission of HIV-1.

We evaluated maternal sexual behavior and injection drug use practices as possible risk factors for vertical transmission of human immunodeficiency virus type 1 (HIV-1). Data were analyzed from the Mothers and Infants Cohort Study, a prospective study in Brooklyn and the Bronx, New York. A total of 207 mother-infant sets were enrolled between 1986 and 1991 and followed for up to 4 years after the enrollment visit during pregnancy. HIV-1 transmission occurred in 49 of 201 mother-infant sets, yielding an overall transmission rate of 24.4% (95% confidence interval (CI) = 18.7% to 31.0%). Increased frequency of vaginal intercourse after the first trimester of pregnancy was positively associated with vertical transmission of HIV-1 (trend p = 0.03). A lifetime history of injection drug use was not associated with vertical transmission. However, a history of combined cocaine and heroin injection after the first trimester of pregnancy was associated with vertical HIV-1 transmission, particularly among women with CD4+ lymphocyte levels of 20% or higher (risk ratio = 4.0; 95% CI = 2.0 to 8.1). Cocaine and heroin injection drug use after the first trimester accounted for most of the relation between preterm birth and vertical HIV-1 transmission in this cohort. Maternal coinfection with hepatitis C virus or human T-cell lymphotropic virus types I and II could not explain these observations, because coinfection with these viruses had no detectable effect on HIV-1 transmission. These results suggest that maternal sexual behavior and injection drug use practices during the second and third trimester of pregnancy may modify the risk of vertical HIV-1 transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Progression to acquired immunodeficiency syndrome is influenced by CD4 T-lymphocyte count and time since seroconversion.

Progression to acquired immunodeficiency syndrome (AIDS) among persons infected with human immunodeficiency virus (HIV) varies considerably and may be influenced by factors such as age, smoking, number of male partners per year, and CD4 T-lymphocyte count. The loss of CD4 lymphocytes is known to be the dominant factor in the progression to AIDS. However, it is unclear whether the effect of the CD4 lymphocyte count is of such importance that persons with similar CD4 cell counts who have been infected for widely different lengths of time have the same risk of AIDS. While a CD4 count is easily obtainable, the precise amount of time since HIV infection is in most circumstances difficult to assess. In the present analysis, 259 Danish and 245 American homosexual men were followed for up to 14 years from 1981 to 1995. Two hundred and one persons seroconverted during the study period, and 112 had developed AIDS before the end of follow-up. CD4 lymphocyte count was highly correlated with the risk of developing AIDS (p < 0.001), but AIDS risk was not affected significantly by either age at infection, smoking, or number of male partners per year (p > 0.20 in all cases). Controlled for CD4 lymphocyte count, time since seroconversion was significant in explaining the risk of AIDS (p = 0.018), with a lower risk being seen during the first 3 years after seroconversion but no effect thereafter. These data confirm the central importance of CD4 lymphocyte level in the progression of HIV disease to AIDS, and suggest that rapid progression within 3 years of infection may be related to factors other than CD4 cell count.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Thrombocytopenia in HIV-infected and uninfected hemophiliacs. Multicenter Hemophilia Cohort study.

To determine the incidence and prognostic significance of thrombocytopenia among hemophiliacs, we analyzed clinical and hematologic data from the Multicenter Hemophilia Cohort study. Nineteen percent of HIV-infected subjects had thrombocytopenia (platelet count of <100,000/mm3) noted at least once, compared to 3% of HIV-uninfected subjects. For HIV-infected subjects, the prevalence of thrombocytopenia rose in the first 5 years after seroconversion and was twice as common in subjects age >35 years compared to younger subjects. The risk increased after an AIDS-defining illness, particularly among older subjects, nearly one-half of whom had thrombocytopenia within 1 year after AIDS. When adjusted for age and CD4-positive lymphocyte counts, thrombocytopenia was associated with an increased risk of death [relative risk (RR) 1.7, 95%CI = 1.2-2.3] but with little change in the risk of progression to AIDS (RR = 1.2, 95%CI = 0.8-1.7). Treatment with zidovudine was associated with a decreased risk of thrombocytopenia (RR = 0.5, 95%CI = 0.3-0.7). Although 59 HIV-infected subjects died of hemorrhage, only 11 (19%) of the 59 had a reported platelet count of <50,000/mm3, and only 2 (3%) of the deaths were temporally associated with thrombocytopenia. Thus, the risk of death was increased for thrombocytopenic HIV-infected hemophiliacs but this was not explained by an increased risk of developing AIDS and was rarely associated with death from bleeding.

Adolescent↗