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Biomedical subjects

J J Goedert

Publications and source records attributed to J J Goedert.

At least 181 records · Page 10Linked to original sources

Serious infections during pregnancy among women with advanced human immunodeficiency virus infection.

Fifty-six human immunodeficiency virus seropositive-women and 76 human immunodeficiency virus seronegative-women had known CD4 cell values and were followed up throughout pregnancy. The women with seronegative results and the 40 with seropositive results and CD4 (helper cell) counts consistently greater than 300 cells/mm3 had no serious infections during pregnancy. Among the 16 with seropositive results and counts that fell below 300 cells/mm3, three developed opportunistic infections, one had pneumonia, and one had a post-cesarean-section abscess. Human immunodeficiency virus seropositive-women with low CD4 counts are at markedly increased risk of serious infections during pregnancy. The consequences of this for fetal health, pregnancy management, maternal well-being, and human immunodeficiency virus testing policies are discussed.

Acquired Immunodeficiency Syndrome↗

Prognostic markers for AIDS.

Human immunodeficiency virus (HIV) infection causes a number of clinical syndromes and many laboratory abnormalities, often heralding the development of the life-threatening opportunistic infections or malignancies that are known as the acquired immunodeficiency syndrome (AIDS). Drawing heavily on the results of prospective cohort studies, particularly those that my colleagues at the National Cancer Institute and I have conducted, this paper reviews the relationship of AIDS to clinical signs and symptoms, immunologic measures, and viral assays. The risk of AIDS in the next 3 years is at least 25 to 50% for HIV-infected subjects who have oral candidiasis, unexplained fever, unexplained weight loss, a CD4+ lymphocyte count below 200 cells/microliter, or combinations of these. Elevated serum levels of beta 2 microglobulin and neopterin also appear to be strong predictive markers of AIDS, but further work is needed in diverse HIV-infected populations, such as intravenous drug users and persons in pattern II countries, such as Haiti and central Africa. Elevated levels of interferon or HIV-p24 antigen in the serum are insensitive but highly specific AIDS markers that may have predictive value independent of CD4 lymphocyte levels. Several potentially valuable immunologic (immunoglobulin levels, tumor necrosis factor, soluble interleukin 2) and virologic (HIV viremia) assays remain to be thoroughly evaluated or technically simplified. Data from prospective cohort studies have provided clinical and laboratory markers of AIDS risk that have proved essential for therapeutic trials and other clinical decisions. As effective treatments for HIV infection and its complications begin to emerge, these marker data will also prove invaluable for mathematic modeling of the scope, course, and public health response to the epidemic.

AIDS-Related Opportunistic Infections↗

Exposure factors for HIV-1 infection among heterosexual drug abusers in New Jersey treatment programs.

In a cross-sectional study of 926 subjects from 10 drug treatment programs conducted in 1984 in New Jersey, the seroprevalence of human immunodeficiency virus (HIV) was 35% overall; 30% in whites, 33% in hispanics, and 46% in blacks (p = 0.01 for comparison of blacks to non-blacks). Univariate analysis showed the seroprevalence of HIV was not associated with age or gender, but did correlate with frequency of cocaine or heroin injection (p trend less than 0.001); frequency of needle sharing (p trend = 0.007); and inversely with levels of education (p = 0.05). The prevalence of HIV was also inversely related to the distance of the treatment center from lower Manhattan; being highest for distances of less than 5 miles from lower Manhattan and lowest for distances of 80 miles, with intermediate rates for the intervening distances (p trend less than 0.001). In multivariate analyses, HIV seropositivity was consistently associated with the frequency of needle sharing (p = 0.02) and less than 12 years (high school level) of education (p = 0.02), but not with black race. However, blacks who shared needles less than once a month had a relative risk of 3.2 (95% CI 1.2, 7.7) while non-blacks who shared less than once a month had a relative risk of only 0.9 (95% CI 0.3, 2.4). The risk in non-blacks increased to more than twofold with more frequent needle sharing. When the analysis was stratified by gender and adjusted for needle sharing and geography, a significant twofold increased risk was observed for female (but not male) subjects who had two or more heterosexual partners compared with those who had one partner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of knowledge of human immunodeficiency virus infection status on sexual activity among homosexual men.

One hundred thirty-four homosexual men from a prospective cohort study of AIDS risk from New York City and Washington D.C. and 139 homosexual men from a similar cohort in Copenhagen and Aarhus, Denmark were questioned regarding their sexual practices and knowledge of their human immunodeficiency virus (HIV) status over the previous 12 months. Seventy percent of Danish men and 63% of U.S. men participated in anal intercourse during the previous 12 months. Knowledge of one's own HIV status by itself did not have any significant effect on participation in anal intercourse, partner number, or condom use. Only 23% of U.S. men and 24% of Danish men always asked potential partners about their HIV status. However, men who did ask were very unlikely to choose a partner of opposite HIV status (p less than 0.006). Danish men were more likely to practice anal intercourse without a condom than were the U.S. men (p less than 0.0001); however, Danes were more likely to be in a concordant monogamous relationship than were the U.S. men (p less than 0.001). Fourteen percent of U.S. men and 21% of Danish men were not aware of their own HIV status and 52% of the U.S. cohort and 31% of the Danes had anal intercourse with a man whose status was unknown to them. Overall, only 32% of American and 53% of Danish homosexual men were practicing completely safe sex. We suggest that education to promote the need for awareness of one's own and one's partner's HIV status should be stressed.

Acquired Immunodeficiency Syndrome↗

Therapy may explain recent deficits in AIDS incidence.

Since the middle of 1987, fewer consistently defined AIDS cases have been reported than expected among homosexual and bisexual men in the United States. This "AIDS deficit" was greater among homosexual and bisexual men in New York City, San Francisco, and Los Angeles, but was also striking among all homosexual and bisexual men in the United States. Deficits were virtually absent among intravenous drug users (IVDUs) in the United States. Three independent sources of data--placebo-controlled trials, pharmaceutical company reports, and the San Francisco Men's Health Study--were used to demonstrate that the amounts of zidovudine (AZT) given prophylactically to those at highest risk of AIDS since March 1987 have been sufficient to account for most of the observed AIDS deficits. Other advances in the medical care of pre-AIDS patients may have combined with AZT to produce the deficits. Other hypothesized explanations were examined and found insufficient to account for the observed AIDS deficits, including: (a) a sudden halt in new human immunodeficiency virus (HIV) infections during the early or mid-1980s; (b) misspecification of the distribution of AIDS incubation times following HIV infection; (c) increasing delays in the reporting of AIDS cases; (d) changes in the surveillance definition of AIDS in 1987; and (e) evolution of attenuated HIV strains. The hypothesis that therapy is affecting national AIDS rates has important implications. Failure to take the effects of therapy into account can lead to serious underestimates by back-calculation of the cumulative numbers infected with HIV and of AIDS incidence over the longer term. Moreover, it appears that AIDS incidence could be retarded in underserved groups, such as IVDUs, by making AZT and other state-of-the-art treatments readily available to AIDS-free patients with advanced immunodeficiency.

Acquired Immunodeficiency Syndrome↗

Kaposi's sarcoma in three HIV-1-infected cohorts.

We describe the Kaposi's sarcoma (KS) experience in three cohorts of homosexual men, subjects with hemophilia, and human immunodeficiency virus type 1 (HIV-1) seroconverters. The risk of KS was higher in HIV-1-infected homosexual men from New York City as compared with Washington, D.C. and was very low in the hemophilia subjects. While KS accounted for a decreasing proportion of AIDS cases in homosexual men, the absolute risk per year did not diminish. Survival was similar after diagnosis of KS vs. opportunistic infection including Pneumocystis carinii pneumonia. Percent CD4+ and CD8+ T cells, and beta 2-microglobulin levels were less abnormal in subjects who later developed KS than in those who developed opportunistic infections; conversely, serum neopterin abnormalities were greater in those who developed KS. The additional risk of KS in homosexual men may explain their apparently higher incidence of AIDS. Further investigation of the differences in intermediate markers of KS and opportunistic infections may shed light on the pathogenesis of these particular manifestations of AIDS.

Acquired Immunodeficiency Syndrome↗

HLA antigen frequencies in HIV-1-related Kaposi's sarcoma.

In an ongoing study of genetic factors that might contribute to disease outcome in HIV-1-infected individuals, HLA antigen (A, B, C, DR and DQ) frequencies in 44 patients with Kaposi's sarcoma (KS) and/or 14 with KS and opportunistic infection (OI) were compared with the frequencies found in 83 HIV-1-seropositive (disease-free) and 87 seronegative homosexual men, or with 50 patients with OI. KS patients had higher frequencies of HLA-B35, -C4, -DR1, and -DQ1 and lower frequencies of HLA-C5 and -DR3 compared to the total control population (N = 170) and to the population at risk (HIV-1-seropositive, disease-free). HLA-DR5, reported by others to be increased in frequency in classical KS as well as HIV-1-related KS, was not found to be increased in the KS cohort. Antigen frequencies in the patients with KS differed from the frequencies in patients with OI by an increase in HLA-A23, -C4, -DR14, and -DR53. These results suggest that genetic factors controlled by the human major histocompatibility complex (MHC) may influence disease outcome in HIV-1-infected homosexual men.

Acquired Immunodeficiency Syndrome↗

Mother-to-infant transmission of human immunodeficiency virus type 1: association with prematurity or low anti-gp120.

In a prospective study of pregnant women infected with human immunodeficiency virus type 1 (HIV-1) in Brooklyn, New York, USA, 16 (29%) of 55 evaluable infants were infected with HIV-1. 9 infants had paediatric acquired immunodeficiency syndrome, 6 had less severe clinical manifestations of HIV-1 infection, and 1 was symptom-free but was seropositive for HIV-1 beyond 15 months of age. The 10 infants born at 37 weeks of gestation or earlier were at higher risk of HIV-1 infection than infants born at 38 weeks of gestation or later (60% vs 22%) but the median age at appearance of disease was approximately 5 months in both groups. The HIV-1 transmission rate was not associated with predelivery levels of maternal T cells, anti-p24, or neutralising antibodies but it was higher, among full-term infants, for those with mothers in the lowest third of the distribution of anti-gp120 levels (53%). On immunoblot, transmitting mothers lacked a gp120 band but not other bands. Protection was not associated with antibody to recombinant peptides from the hypervariable region of the major neutralising gp120 epitope, and the anti-gp120 endpoint dilution titre was similar in transmitting and non-transmitting mothers. Mothers of uninfected full-term infants appear to confer immunological protection against HIV-1 infection of their offspring by way of a high-affinity antibody to a gp120 epitope, whose specificity has importance for vaccine development and possibly perinatal immunotherapy.

Acquired Immunodeficiency Syndrome↗

A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia.

We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (+/- SE) of 13.3 +/- 5.3 percent for ages 1 to 17, 26.8 +/- 6.4 percent for ages 18 to 34, and 43.7 +/- 16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P less than or equal to 0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease.

Acquired Immunodeficiency Syndrome↗

Predictive markers for the acquired immunodeficiency syndrome (AIDS) in hemophiliacs: persistence of p24 antigen and low T4 cell count.

STUDY OBJECTIVE: To investigate the predictive value of assays for human immunodeficiency virus (HIV) p24 antigen, p24 antibody, and gp120 antibody compared with T4 cell counts. DESIGN: Prospective cohort selected from persons who had HIV-antibody seroconversion. PATIENTS: Eighty-seven persons with hemophilia with an actuarial cumulative acquired immunodeficiency syndrome (AIDS) incidence of 26% (CI, 12% to 40%), 8 years after HIV-antibody seroconversion. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Human immunodeficiency virus p24 antigen was detected in 8 of 74 (11%) of the patients without AIDS and 7 of 13 (54%) of the patients with AIDS. The 2-year actuarial incidence of AIDS was 24% (CI, 0% to 48%) after detection of p24 antigen, 16% (CI, 0% to 34%) after loss of p24 antibody, 20% (CI, 0% to 45%) after loss of gp120 antibody, 31% (CI, 15% to 47%) after a T4 count of less than 200 cells/microL, and 67% (CI, 31% to 100%) after a T4 count of less than 200 cells/microL among those patients positive for p24 antigen. Very low numbers of T4 and T8 lymphocytes, presence of p24 antigen in serum, and absence of p24 antibody all had some predictive value. However, only p24 antigen (relative hazard 6.0, P = 0.008) and T4 counts (relative hazard 5.3, P = 0.002 with T4 count less than 200 cells/microL) independently predicted AIDS up to 12 months before diagnosis. CONCLUSIONS: Strong predictors of AIDS are p24 antigenemia or low T4 counts. Detection of p24 antigen is highly specific and complementary to the greater sensitivity of low T4 counts. These findings have important implications regarding prognosis, counseling, and the planning of clinical trials.

Acquired Immunodeficiency Syndrome↗

Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I.

Adult T-cell leukemia/lymphoma (ATL), a malignancy of mature CD4-positive lymphocytes, has been etiologically linked to the human retrovirus HTLV-I. Although a long latent period is suggested from migrant studies, little prospective information on the risk of developing ATL among persons with HTLV-I infection is available. We present here a model for ATL risk based upon age- and sex-specific HTLV-I seroprevalence data from a cross-sectional survey of 13,000 Jamaicans and ATL incidence data from a 2 1/2-year case-control study. By examining the age-specific incidence of ATL relative to both adult and childhood-acquired seropositivity versus childhood-acquired seropositivity alone, we provide evidence in support of the hypothesis that childhood infection with HTLV-I is important to the development of ATL. Using this model, the cumulative lifetime risk of ATL for those infected before age 20 is estimated to be 4.0% for males and 4.2% for females. Under this hypothesis, HTLV-I-associated diseases with shorter latent periods, such as tropical spastic paraparesis, should have a higher incidence in adult females than in adult males.

Adolescent↗

Immunosuppression in pregnant women infected with human immunodeficiency virus.

One hundred two pregnant women at high risk of infection with the human immunodeficiency virus (62 who were drug abusers and 40 of Haitian origin) were prospectively examined for immunologic changes during and after pregnancy. Among the 63 human immunodeficiency virus-negative women, levels of CD4+ (helper) cells fell to a nadir at 8 weeks before delivery and rose rapidly just before delivery. The level of CD8+ (cytotoxic/suppressor) cells rose slowly from midpregnancy to delivery. Among the 37 human immunodeficiency virus-positive pregnant women, levels of CD4+ cells fell during pregnancy (except for a transient weak increase just before delivery) and did not recover in the postpartum period. Levels of CD8+ cells were consistently higher in human immunodeficiency virus-positive than human immunodeficiency virus-negative women. Post partum the CD8+ cells in human immunodeficiency virus-negative women stabilized at delivery levels, whereas they increased greatly in human immunodeficiency virus-positive women. The loss of CD4+ cells in human immunodeficiency virus-positive women appeared to be faster during pregnancy than in the postpartum period. These data support the hypothesis that pregnancy may accelerate human immunodeficiency virus-induced depletion of CD4+ cells and increase the risk of acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

A method for the rapid screening of human blood samples for the presence of HIV-1 sequences: the probe-shift assay.

In theory, screening directly for the human immunodeficiency virus (HIV) DNA has advantages over screening for HIV-related antibodies; however, the HIV genome appears to be present only in a small fraction of peripheral blood cells from infected individuals. The polymerase chain reaction (PCR) specifically amplifies defined DNA segments, permitting the identification of specific DNA segments even if they are present in a fraction of cells. HIV-derived PCR-amplified segments have been detected by Southern transfer, "dot-blot" hybridization, and digestion with restriction endonucleases. Unfortunately, PCR may amplify not only the single segment of interest but also irrelevant segments, which can be incorrectly identified as HIV related. We describe here an alternative approach to specific detection of PCR-amplified DNA segments, the probe-shift assay, that is simpler, faster, and less subject to erroneous identification than the previously described techniques. The probe-shift assay relies on the hybridization of an appropriately labeled oligonucleotide probe to the amplified segment in solution. The hemiduplex formed between the amplified DNA and the probe is detected following fractionation on nondenaturing gels. This procedure is sufficiently sensitive to detect a single infected cell in the presence of more than 10(5) uninfected cells and has been applied directly to clinical samples.

Acquired Immunodeficiency Syndrome↗

Urinary neopterin concentrations vs total neopterins for clinical utility.

Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV-1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4+ T-cell counts and CD4+/CD8+ T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for clinical diagnosis. However, when measuring total neopterins, which includes oxidation of 7,8-dihydroneopterin to neopterin, more strict requirements of sample collection and handling are necessary to avoid degradation of the 7,8-dihydro derivative.

Acquired Immunodeficiency Syndrome↗

Censoring in an epidemic with an application to hemophilia-associated AIDS.

In epidemiologic studies of infectious diseases, the times of infection may be known only up to an interval. A two-stage parametric regression model is proposed for the analysis of cohort studies during an epidemic in which the exact times of infection cannot be ascertained. The methods permit joint estimation of the effects of covariates both on the risk of infection and the risk of progression to clinical disease once infected. The methodology is applied to a cohort of hemophiliacs who were at risk of infection with the AIDS virus. It was found that hemophiliacs with severe Type A hemophilia were at highest risk of infection, and the risk of infection increased sharply in the early 1980s. Hemophiliacs who were over the age of 20 at infection were at higher risk of progression to AIDS than hemophiliacs who were under age 20. The estimate of the cumulative probability of developing AIDS within t years of infection (the incubation period distribution) for hemophiliacs over age 20 was 1 - exp(-.0021t2.516). Since follow-up in this cohort was restricted to about 10 years from infection, estimates of the incubation period distribution beyond 10 years depend on model extrapolation and should be interpreted cautiously.

Acquired Immunodeficiency Syndrome↗

Risk of human immunodeficiency virus (HIV-1) infection among laboratory workers.

In a prospective cohort study of 265 laboratory and affiliated workers, one individual with no recognized risk factors for human immunodeficiency virus type 1 (HIV-1) infection was HIV-1 seropositive at the time of entry into the study. Molecular analyses of two HIV-1 isolates derived in two independent laboratories from a blood sample from this worker showed that the isolates were indistinguishable from a genotypic form of HIV-1 present in the H9/HTLV-IIIB cell line. Exposure to this strain of virus most probably occurred during work with concentrated virus or culture fluids from virus-producing cell lines under standard Biosafety Level 3 containment. Although no specific incident leading to this infection has been identified, undetected skin contact with virus culture supernatant might have occurred. This worker was the only one found to be positive among the subgroup of 99 workers who shared a work environment involving exposure to concentrated virus. The incidence rate of 0.48 per 100 person-years exposure indicates that prolonged laboratory exposure to concentrated virus is associated with some risk of HIV-1 infection, which is comparable to the risk for health care workers experiencing a needle stick exposure. While none of the ten workers with parenteral exposure to HIV-1 in this cohort became infected, a worker in another laboratory did seroconvert following an injury with a potentially contaminated needle. Strict Biosafety Level 3 containment and practices should be followed when working with concentrated HIV-1 preparations, and further refinement of the procedures may be necessary.

Acquired Immunodeficiency Syndrome↗