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J J Goedert

Publications and source records attributed to J J Goedert.

At least 145 records · Page 8Linked to original sources
PubMed1994

Perinatal transmission of HIV type 1: associations with maternal anti-HIV serological reactivity. Mothers and Infants Cohort Study and the HIV-1 Perinatal Serology Working Group.

As a hypothesis-generating study of large regions of the human immunodeficiency virus type 1 (HIV-1) envelope, we collaborated with several laboratories to test sera from subgroups of 65 HIV-1-positive pregnant women, 18 (28%) of whom transmitted the virus to their infants. Assays included neutralizing antibodies to HIVLAI and reactivity to 102 HIV-1 Env peptides with sequences based on strains LAI, MN, SC, RF, and WMJ-2 as well as several clinical isolates, spanning about 65% of gp120 and about 80% of gp41. Results for the V3 loop and for neutralizing activity were conflicting and for the most part did not reach statistical significance. Transmission risk appeared lower with reactivity to a few gp41 epitopes (amino acids 571-585, 736-750, and perhaps 650-663), whereas risk appeared higher with reactivity to two gp120 epitopes (amino acids 466-480 and 475-486) and one gp41 epitope (amino acids 547-576). However, these associations could have occurred simply by chance because such a large number of peptides was tested. With independently synthesized peptides, results between laboratories often were inconsistent. However, reproducibility was good (rank correlation coefficient > or = 0.78) when the same protocols and peptides were used. Although this study could not identify a humoral immune response to linear Env peptides that consistently and broadly protected against perinatal transmission of HIV-1, there were regions of gp120 and gp41 that should be evaluated in larger cohorts and with techniques to investigate potential conformational epitopes and neutralization to autologous or clinical isolates of HIV-1 from the community.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Effect of age at seroconversion on the natural AIDS incubation distribution. Multicenter Hemophilia Cohort Study and the International Registry of Seroconverters.

OBJECTIVE: To estimate the age-specific relative risk of progression from HIV seroconversion to onset of AIDS in hemophiliacs and homosexual men. DESIGN: Prospective follow-up data from HIV seroconversion to AIDS was analyzed for hemophiliacs in the Multicenter Hemophilia Cohort Study and for homosexual men in the International Registry of Seroconverters. Follow-up was censored at 1 July 1987 to obtain natural history estimates unaffected by therapies that were widely used after this date. The age-specific relative hazard of progression was estimated using nonparametric proportional hazards models and the baseline hazard function was described using spline models. RESULTS: Among the 373 children and adults with hemophilia and the 1020 adult homosexual men, each 10-year increment in age at seroconversion was associated with a 1.6- and 1.4-fold increase in the hazard of progression, respectively. The effect of age was highly significant among hemophiliacs. The magnitude of the effect was consistent in different cohorts of homosexual men, although it was not nominally significant. Furthermore, there was a significant increase (1.9-fold higher) in progression rates among homosexual men above rather than below 35 years of age at seroconversion. After adjusting for age, progression rates among hemophiliacs were significantly slower, possibly because Kaposi's sarcoma was rare. In both groups, the annual hazard rate increased during the first 5 years after seroconversion, but broad confidence limits prevented us from establishing hazard trends beyond this time. CONCLUSIONS: Estimates of the aggregate incubation time distribution were substantially shorter in older compared with younger individuals. The increasing risk with age was similar in hemophiliacs and homosexual men, suggesting that age is an endogenous host factor. These findings can be incorporated into newly developed backcalculation models to estimate HIV infection incidence by age group from age-specific AIDS surveillance data.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Sexual behaviour survey in a rural area of northwest Tanzania.

OBJECTIVE: Little is known about variations in patterns of sexual behaviour in different countries, cultures, and subpopulations that determine the spread of HIV-1. Quantitative studies are required to improve understanding. METHODS: To assess reported patterns of sexual behaviour, we administered a standardized questionnaire to 416 men and 498 women aged 15-49 years from a rural population in northwest Tanzania. RESULTS: Reported levels of sexual activity were highest in men and among younger age groups. The number of sexual partners and number of sex acts per unit of time were strongly correlated: men reported 10 times as many lifetime partners than women. Frequency of sexual partner exchange plateaued earlier in women (by age 25 years) than in men (by age 35 years). For the great majority, age of first intercourse was 15 years or younger; older subjects were older at first intercourse and had fewer lifetime partners than younger subjects. CONCLUSIONS: This age-related pattern suggests that more recent birth cohorts have behaviour patterns that increase the risk of sexually transmitted infectious agents such as HIV. Preventive education programmes should be targeted at young adults, who adopt higher risk profiles of frequent partner exchange linked with first intercourse at an early age.

Adolescent↗
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

Relationship of CD4 lymphocyte counts to survival in a cohort of hemophiliacs infected with HIV. Multicenter Hemophilia Cohort Study.

Although CD4 positive lymphocyte counts are important predictors of clinical events in persons infected with human immunodeficiency virus (HIV), little is known about their predictive value for survival. We analyzed CD4 counts obtained regularly since 1983 with regard to survival in a multicenter cohort study of 921 HIV-infected hemophiliacs of whom 177 have died. Dates of seroconversion were determined from stored serum samples. Cumulative mortality and actuarial survival rates were calculated from the first time the mean of two consecutive CD4 counts decreased from levels of > 500 to 200-499, 100-199, 50-99, and < 50 cells/microliter. The death rate per 100 patient years of observation was 0.87 (95% CI 0.27, 1.47) for those with CD4 counts of > 500 cells/microliter and increased progressively to 26.23 (95% CI 21.29, 31.17) for those with CD4 counts of < 50/microliter. HIV-related deaths occurred in 50 of 58 who died with CD4 counts of < 300/microliter compared to 0 of 6 who died with CD4 counts of > 500/microliter. The median CD4 count most proximal to death was 39.5 (range, 1-945). The 10-year actuarial estimate of survival from seroconversion was 77.3 +/- 2% for 546 persons who seroconverted at age > or = 18 years compared to 90.5 +/- 2% for 375 persons who seroconverted at age < 18. Survival decreased at each CD4 level to a median of 27 months at CD4 counts of < 50/microliter. At each CD4 level, younger patients survived longer than older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

HIV-1 infection incidence among persons with hemophilia in the United States and western Europe, 1978-1990. Multicenter Hemophilia Cohort Study.

We studied human immunodeficiency virus type 1 (HIV-1) infection incidence over time in a 16-center cohort of hemophiliacs in the United States and Europe and estimated the most likely date of seroconversion for all seropositive subjects. Five U.S. centers enrolled subjects independent of HIV-1 status, whereas 11 centers preferentially included seropositive subjects. We obtained unbiased estimates of HIV-1 infection incidence rates from the five centers and estimated dates of seroconversion from the distribution seen among seropositives from all centers. In the five-center cohort, infection incidence began in 1978, peaked in October 1982 at 22 infections per 100 person-years at risk, and declined to 4 per 100 person-years by July 1984. Few infections occurred after 1987, and by that time, 50% of the cohort had become infected. Median seroconversion dates for subgroups of all seropositives ranged from July 1980 to December 1983, depending on the dose and type of factor concentrate. Median dates in Europe ranged from September 1981 to March 1983 and reflected the use of products manufactured from American plasma. Infection incidence apparently peaked about the same time that public health interventions were introduced to reduce transmission. These interventions, including heat treatment of factor concentrates and deferral of high-risk donors, have prevented HIV-1 infection from becoming endemic among younger birth cohorts of persons with hemophilia.

Adolescent↗
PubMed1993

HTLV-I and HTLV-II world-wide distribution: reanalysis of 4,832 immunoblot results.

Mapping the geographic distribution of human T-lymphotrophic virus types 1 and 2 (HTLV-I and -II) has been complicated because conventional serologic approaches cannot distinguish between these 2 viruses. To more precisely define the epidemiology of HTLV-I and HTLV-II, we evaluated a convenience sample of 4,832 HTLV-I immunoblot results from over 140,000 samples screened for HTLV-I, collected in 16 countries for 35 separate studies. An algorithm that compares reactivity against p19 and p24, 2 gag (HTLV-I core) proteins, was employed to characterize the immunoblots: type I, p19 stronger than p24 (presumptive HTLV-I), type 2, p24 stronger than p19 (presumptive HTLV-II), or indeterminate (p19 and p24 weakly positive or p19 weakly positive in the presence of p21e). Geographic areas could be grouped into 4 patterns. Patterns A (> 75% type I) and B (> 75% type 2) were usually observed where the specific type of HTLV or its characteristic diseases had been found. Pattern C (mixed type 1 and 2 pattern) was observed predominantly in intravenous-drug-using and other populations in which both virus types have been reported. Pattern D (> 10% indeterminate), suggests the presence of non-specific reactivity, perhaps resulting from exposure to non-virus-related antigens or an HTLV-related virus. HTLV-I predominates in southern Japan, the South Pacific, parts of West Africa, and in Afro-populations of the Western hemisphere. HTLV-II clusters in Native American populations and among intravenous drug users. Pattern-D areas in Africa and Venezuela might prove to be fertile in the search for new and variant HTLV virus types.

Blotting, Western↗
PubMed1993

Loss of high-responder inhibitors in patients with severe hemophilia A and human immunodeficiency virus type 1 infection: a report from the Multi-Center Hemophilia Cohort Study.

To evaluate the effects of human immunodeficiency virus type 1 (HIV-1) infection on the loss of factor VIII alloantibodies, we identified 77 patients with a history of inhibitors from among a large cohort of HIV-1-infected participants enrolled in a natural history study of HIV-1 infection in hemophilia. Fifty-six patients were high responders with inhibitors titers greater than 5 Bethesda Units (BU) measured on at least one occasion. From May 1985 to December 1989, 13 of the high-responder patients were rechallenged with factor VIII concentrates after several years of treatment with other plasma products. All exhibited excellent hemostasis upon reinstitution of factor VIII. Seven of the 13 patients (11.3-46.3 years of age) were in the advanced stages of HIV-1 infection at the time of rechallenge. Inhibitor titers measured subsequent to the reinstitution of factor VIII were consistently less than 1 BU in five of these seven patients. The remaining six patients (6.1-57.5 years of age) had mild to moderate CD4+ lymphocyte depletion (absolute CD4+ cells: 262-935/mm3) at the time of factor VIII rechallenge. Follow-up inhibitor titers were negative 7-42 months after consistent factor VIII use in these six patients. The lack of anamnestic response to factor VIII in all 13 patients who were rechallenged indicates that HIV-1-infected patients who have a history of high-responder inhibitors frequently benefit from the reintroduction of factor VIII use for the control of bleeding, regardless of their stage of HIV-1 disease.

Adult↗
PubMed1993

A 90-kDa protein serum marker for the prediction of progression to AIDS in a cohort of HIV-1+ homosexual men.

Levels of a 90-kDa protein (90K), recently reported as a possible marker of HIV-1 infection, were serially examined in a group of HIV-1-infected (HIV-1+) and uninfected (HIV-1-) subjects drawn from the same cohort of homosexual men. The first phase of the study included 61 HIV-1+ AIDS-free subjects 4 years (+/- 6 months) postseroconversion and 75 contemporaneous unifected subjects. Two years later, a subset of 35 HIV-1+ AIDS-free subjects and 72 HIV-1- controls was examined. Mean 90K levels for HIV-1+ subjects were significantly higher than for contemporaneous HIV-1- subjects both 4 and 6 years postseroconversion (p < 0.0001). A significantly more rapid progression to AIDS was seen in HIV-1+ subjects with high 90K levels both 4 years (p = 0.01) and 6 years (p = 0.003) postseroconversion. Four years postseroconversion, 90K was significantly correlated with CD8 cell percent, interferon, neopterin, and beta 2-microglobulin (p < 0.05). Two years later, significant correlations were seen between 90K levels and CD4 cell percent, CD4 cell number, and beta 2-microglobulin (p < 0.05). Stepwise-stepdown regression modeling using 90K, CD4 cell percent, interferon, and beta 2-microglobulin levels 4 years postseroconversion showed that the predictive value of a trivariate model of 90K-interferon-CD4 percent was better than any univariate or bivariate model. We conclude that the 90K protein may be a useful predictor of progression to AIDS in HIV-1+ patients, particularly in combination with the established markers of CD4 cell percent and interferon.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cytomegalovirus infection and risk of AIDS in human immunodeficiency virus-infected hemophilia patients. National Cancer Institute Multicenter Hemophilia Cohort Study Group.

The effects of prevalent and incident cytomegalovirus (CMV) infection on human immunodeficiency virus (HIV) disease progression were examined in 393 hemophilia patients with known dates of HIV seroconversion. Of the cases, 191 (49%) had IgG antibody to CMV in their earliest stored sera (median date, November 1983). CMV-seropositive subjects were one and a half times more likely to develop AIDS, and they were also older than CMV-negative subjects. Adjusted for age, CMV seropositivity was not associated with the development of AIDS. In age-adjusted analyses, CMV-seropositive subjects had a small, but statistically insignificant, decrease in survival after HIV seroconversion. Older subjects were more likely to CMV seroconvert by the time of their latest available serum samples (P = .03). CMV seroconverters were five times more likely to develop clinical CMV disease than were subjects initially CMV-positive (P = .02). To avoid this source of serious morbidity, CMV-seronegative hemophiliacs with HIV infection should not be exposed to cellular blood products or body fluids from CMV-seropositive donors.

Acquired Immunodeficiency Syndrome↗