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L M Mofenson

Publications and source records attributed to L M Mofenson.

54 records · Page 3Linked to original sources
PubMed1995

Sinusitis in children infected with human immunodeficiency virus: clinical characteristics, risk factors, and prophylaxis. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

The clinical presentation, radiological and laboratory evaluation, treatment, and risk factors of sinusitis in a cohort of 376 human immunodeficiency virus (HIV)-infected children from a placebo-controlled clinical trial of intravenous immunoglobulin (IVIG) as prophylaxis for infections were examined. Ninety-five episodes of sinusitis were described in 60 patients; one-third of the patients had two or more episodes. Sinusitis episodes were commonly associated with nonspecific, chronic symptoms (67.4%, persistent nasal discharge; 54.7%, nocturnal or persistent cough), whereas symptoms more specific to acute sinusitis were less frequent (17.9%, headache or facial pain; 9.5%, periorbital swelling; 25.3%, temperature of > or = 102 degrees F; 9%, total white blood cell count of > or = 15,000/mm3). The sinuses primarily involved were the maxillary sinus (85.9%) and the ethmoidal sinus (42.3%); 36% of episodes involved two or more sinuses. Preceding respiratory infections did not appear to increase the risk of sinusitis, and CD4+ lymphocyte counts in children with and without sinusitis did not differ. Neither monthly IVIG prophylaxis nor three times weekly trimethoprimsulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia decreased the risk of sinusitis. Sinusitis in HIV-infected children is most often subacute and recurrent. Evaluations of new modalities for prophylaxis for sinusitis are needed.

AIDS-Related Opportunistic Infections↗
PubMed1994

The role of obstetric interventions in the prevention of pediatric human immunodeficiency virus infection.

By the end of the decade 10 million children will be infected with human immunodeficiency virus. Several potential means of preventing vertical transmission of human immunodeficiency virus are under study. Although the perinatal use of antiretroviral agents can prevent some of these infections, those agents are neither uniformly effective nor universally available. A significant portion of vertical transmission may be an intrapartum phenomenon, potentially amenable to obstetric interventions, such as cesarean section or vaginal virucides. The utility of these obstetric interventions will be determined in large part by the timing of vertical transmission. This work reviews the evidence that human immunodeficiency virus can be transmitted during the intrapartum period and critically reviews the data supporting a role for obstetric interventions. Finally, we outline the necessary elements for the conduct of a conclusive efficacy trial and delineate a mechanism to arrive at a definitive standard of care in the absence or anticipation of a trial.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Crossover of placebo patients to intravenous immunoglobulin confirms efficacy for prophylaxis of bacterial infections and reduction of hospitalizations in human immunodeficiency virus-infected children. The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

After completion of a placebo-controlled trial of intravenous immunoglobulin (IVIG) infection prophylaxis, patients were offered open label IVIG and optional participation in a follow-up study. The purpose of the follow-up study was to evaluate the IVIG effect in original placebo recipients and longevity of IVIG benefit in original IVIG recipients. Of 212 human immunodeficiency virus-infected children on study at trial closure, 148 (67 of 98 (68%) placebo and 81 of 114 (71%) IVIG patients) received open label IVIG for a mean of 16 months. When open label IVIG was begun, 45% were receiving trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia (43% of placebo and 47% of IVIG patients) and 54% were receiving zidovudine (55% of placebo and 53% of IVIG patients). In patients who received placebo during the original study, the rate of serious bacterial infections was significantly lower after change to open label IVIG (estimated 15.8 fewer episodes/100 patient years; 95% confidence interval, 3.2 to 28.5; P = 0.014). Similar findings were observed for minor bacterial infections (estimated 61.2 fewer/100 patient years; 95% confidence interval, 29.2 to 93.3; P < 0.001) and hospitalizations (estimated 43.7 fewer/100 patient years; 95% confidence interval, 27.7 to 59.6; P < 0.001). Decreases were observed whether or not trimethoprim-sulfamethoxazole prophylaxis was being given at the time open label IVIG was begun. In patients who received IVIG during the original study, no significant difference was seen in infections or hospitalizations after change to open label IVIG.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
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↗
PubMed1993

Immunologic targets of HIV infection: T cells. NICHD IVIG Clinical Trial Group, and the NHLBI P2C2 Pediatric Pulmonary and Cardiac Complications of HIV Infection Study Group.

One of the principal targets of HIV infection is the human peripheral blood CD4+ T cell, resulting in progressive CD4+ lymphocyte loss. Hypothesized mechanisms for this loss include apoptosis, cytolytic reactions, V-beta gene deletion of the T-cell receptor (TCR) by superantigens, CD4+ lymphocyte syncytium formation, and autoimmune reactions. In adults with HIV infection, the critical decline in CD4+ lymphocyte number that heralds the onset of AIDS-defining conditions is well characterized, whereas in infants and children the critical level of CD4+ cells predisposing to the development of AIDS-defining conditions or mortality is not fully characterized, due to an incomplete knowledge of CD4+ lymphocyte number and changes with age in normal and HIV-infected children. In a prospective study of 317 infants born to HIV-infected women, early results show that the monthly change in absolute CD4+ lymphocyte number over a 3- to 9-month period in HIV-infected infants was -109 cells/mm3 per month, at least double the rate of decline measured in HIV-noninfected infants in the study or that calculated from normal infants' values reported in the literature. In other clinical studies in HIV-infected infants and children, it was possible to study the effect of low CD4+ cell counts on clinical status and mortality. In HIV-infected pediatric patients younger than 1 year, it was possible to correlate low CD4+ cell number with advanced disease status (CDC pediatric class P-2). It was also possible to correlate extremely low CD4+ cell counts (< 200 cells/mm3) in HIV-infected children with a significant risk of mortality within the next 3 months of life. Sequential CD4+ cell analysis of HIV-high-risk infants will delineate the rate of HIV-related decline in CD4+ cells, thus facilitating the diagnosis of HIV infection and aiding in identification of HIV-infected children at high risk of disease progression or death.

CD4-Positive T-Lymphocytes↗
PubMed1993

Intravenous immune globulin for the prevention of infections in children with symptomatic human immunodeficiency virus infection.

Infection with human immunodeficiency virus (HIV) causes a progressive immunodeficiency, often manifested in adults by the development of infections with relatively rare, opportunistic organisms. However, in HIV-infected children, recurrent serious infections with common encapsulated bacteria, as well as recurrent minor bacterial and viral infections, may be early and frequent manifestations of HIV disease. The use of i.v. immune globulin (IVIG) has been shown to prevent infections in patients with primary immunodeficiency and in uncontrolled studies of HIV-infected children. This article reviews the problem of and immunologic predisposition for recurrent infections in pediatric HIV infection and reports on the use of IVIG for prophylaxis. Updated analysis from the National Institute of Child Health and Human Development IVIG Clinical Trial, a multicenter, double-blind, placebo-controlled trial of the safety and efficacy of IVIG for the prevention of infections in children with symptomatic HIV infection, is presented. Between March 1988 and January 1991, 376 children with clinical or immunologic evidence of HIV disease who were randomized to receive IVIG or albumin placebo were enrolled in this trial. In children with an entry CD4+ count of 200/mm3 or higher, IVIG significantly increased the time free from serious bacterial infections and significantly decreased the rates of minor bacterial infections and viral infections.

AIDS-Related Opportunistic Infections↗
PubMed1993

Effect of intravenous immunoglobulin (IVIG) on CD4+ lymphocyte decline in HIV-infected children in a clinical trial of IVIG infection prophylaxis. The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

Our objective was to evaluate the effect of intravenous immunoglobulin (IVIG) on absolute CD4+ lymphocyte count (CD4+ count) trends in human immunodeficiency virus- (HIV) infected children enrolled in a trial of IVIG for infection prophylaxis. To that end, we conducted a randomized, double-blind, outpatient trial comparing subjects treated with 400 mg per kilogram of IVIG every 28 days with those given 0.1% albumin placebo. CD4+ counts were measured at entry and every 12 weeks. Twenty-eight clinical centers in mainland United States and Puerto Rico participated. Previous reports showed IVIG efficacy for infection prophylaxis in 313 patients with entry CD4+ counts of > or = 0.20 x 10(9)/L (> or = 200/mm3). Two hundred and seventy-seven (89%) of these 313 children had three or more CD4+ counts measured during the trial and were included in evaluation of CD4+ count trends. Rates of CD4+ count decline, as measured by regression slopes, were compared between IVIG and placebo groups using generalized linear models, comparing unadjusted, age-adjusted, and standardized age-adjusted data. Potential covariate effects were assessed by modeling change in CD4+ count in terms of log change between successive measurements. Age-adjusted slope analysis showed slowing of CD4+ count decline by 13.5 cells/mm3 per month in IVIG compared with placebo recipients (95% confidence interval, 3.1-23.9, p = 0.012). Modeling log change between measurements documented a beneficial effect of IVIG that was cumulative over time and independent of other therapies. Occurrence of serious bacterial infection in the interval before CD4+ count measurement or death was independently associated with more rapid CD4+ count decline (p = 0.01 and p = 0.008, respectively). Zidovudine therapy was associated with a transient increase in CD4+ count. Benefits of IVIG include slowing of CD4+ count decline as well as previously reported reductions in serious and minor bacterial and viral infections in subjects with entry CD4+ counts of > or = 0.20 x 10(9)/L. This finding provides corroboration for the hypothesis that immunologic mechanisms contribute to the pathogenesis of CD4+ decline in HIV infection.

Age Factors↗
PubMed1992

Human immunodeficiency virus infection in pregnant women under care at AIDS clinical trials centers in the United States.

The federal government supports a nationwide network of medical centers to evaluate promising therapies against the human immunodeficiency virus (HIV) and the opportunistic infections and cancers that characterize AIDS. Forty-five obstetricians from the 49 medical centers receiving federal research support for the conduct of AIDS-related clinical trials, in preparation for a meeting, provided summary information about the number and clinical status of the known HIV-infected pregnant women under their care and the prenatal screening policies for HIV infection at their institutions. In the 12-month period before December 1989, an estimated 1000-1801 HIV-infected women delivered at these centers. The majority (82%) were asymptomatic, 12% were symptomatic, and 6% had AIDS. Routine T-cell testing of infected women was done as part of prenatal care in only 30 of 45 centers. Pneumocystis carinii pneumonia was reported in 35 women. Zidovudine was administered during pregnancy in 29 women. Formal prenatal screening policies have been implemented at the majority (43 of 45) of the medical centers. Most of the infected women identified at these centers chose to continue the pregnancy. With the increasing incidence of HIV infection in women, information concerning the clinical and immunologic state of pregnant infected women and the present use of antiretroviral and other related therapeutics during pregnancy can guide the approach to women's health care and is crucial to the design and implementation of AIDS clinical trials.

Clinical Trials as Topic↗
PubMed1991

Passive immunization to prevent mother-infant transmission of human immunodeficiency virus: current issues and future directions.

A definitive conclusion regarding the potential for the presence of neutralizing antibody to epitopes of the V3 loop to attenuate or prevent vertical transmission of HIV infection cannot be made based on the results of these four studies. However, the studies provide an intriguing suggestion that it may be possible to identify an epitope or array of epitopes from the V3 loop of judiciously selected HIV isolates that could induce protective immunity against HIV. Future collaborative studies are needed to standardize and independently validate the various assays. A recent conference, Early Diagnosis of HIV Infection in Infants, sponsored by the National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases and the Centers for Disease Control, provided a forum to facilitate exchange of information among researchers in this field, and encourage future collaborative efforts. If one or more subpopulations of anti-gp120/V3 loop or other neutralizing antibodies are indeed associated with a decreased risk of maternal-infant transmission, it becomes important to determine whether these antibodies are protective per se or are merely surrogate markers of a different mechanism. The former conclusion seems to be supported by the finding of HIV-specific antibodies in seropositive persons' saliva and breast milk, both of which have relatively low infectivity, although the potential neutralizing activities of these antibodies have not been adequately evaluated. The development and testing of a highly specific (monoclonal antibody-derived) passive immunotherapy will probably be required to answer this question.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Measles antibody: reevaluation of protective titers.

A school blood drive before a measles outbreak permitted correlation of preexposure measles antibody titers with clinical protection using the plaque reduction neutralization (PRN) test and an EIA. Of 9 donors with detectable preexposure PRN titer less than or equal to 120, 8 met the clinical criteria for measles (7 seroconfirmed) compared with none of 71 with preexposure PRN titers greater than 120 (P less than .0001). Seven of 11 donors with preexposure PRN titers of 216-874 had a greater than or equal to 4-fold rise in antibody titer (mean, 43-fold) compared with none of 7 with a preexposure PRN titer greater than or equal to 1052 (P less than .02). Of 37 noncases with preexposure PRN titer less than 1052, 26 (70%) reported one or more symptoms compared with 11 (31%) of 35 donors with preexposure PRN titers greater than or equal to 1052 (P less than .002). By EIA, no case had detectable preexposure antibody; the preexposure geometric mean titer of asymptomatic donors (220) was not significantly higher than that of symptomatic donors who did not meet the clinical criteria for measles (153) (P = .10). The study suggests that PRN titers less than or equal to 120 were not protective against measles disease and illness without rash due to measles may occur in persons with PRN titers above this level.

Adult↗
PubMed1988

Epidemic giardiasis caused by a contaminated public water supply.

In the period November 1, 1985 to January 31, 1986, 703 cases of giardiasis were reported in Pittsfield, Massachusetts (population 50,265). The community obtained its water from two main reservoirs (A and B) and an auxiliary reservoir (C). Potable water was chlorinated but not filtered. The incidence of illness peaked approximately two weeks after the city began obtaining a major portion of its water from reservoir C, which had not been used for three years. The attack rate of giardiasis for residents of areas supplied by reservoir C was 14.3/1000, compared with 7.0/1000 in areas that received no water from reservoir C. A case-control study showed that persons with giardiasis were more likely to be older and to have drunk more municipal water than household controls. A community telephone survey indicated that over 3,800 people could have had diarrhea that might have been caused by Giardia, and 95 per cent of households were either using alternate sources of drinking water or boiling municipal water. Environmental studies identified Giardia cysts in the water of reservoir C. Cysts were also detected in the two other reservoirs supplying the city, but at lower concentrations. This investigation highlights the risk of giardiasis associated with unfiltered surface water systems.

Adult↗
PubMedDate not supplied

Prophylactic intravenous immunoglobulin in HIV-infected children with CD4+ counts of 0.20 x 10(9)/L or more. Effect on viral, opportunistic, and bacterial infections. The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

OBJECTIVE: To evaluate the efficacy of intravenous immunoglobulin (IVIG) for prevention of viral, opportunistic, and minor bacterial infections in children infected with human immunodeficiency virus (HIV). DESIGN: Randomized, double-blind, placebo-controlled, outpatient clinical trial comparing subjects treated with 400 mg of IVIG per kilogram of body weight every 28 days with those given albumin placebo. SETTING: Twenty-eight clinical centers in mainland United States and Puerto Rico. PATIENTS: Three hundred seventy-six children infected with human immunodeficiency virus with clinical or immunologic evidence of HIV disease, 313 of whom had entry CD4+ counts of at least 0.20 x 10(9)/L (greater than or equal to 200/mm3). MAIN OUTCOME MEASURES: The incidence of laboratory-proven and clinically diagnosed viral, opportunistic, and bacterial infections. MAIN RESULTS: Viral infections and minor bacterial infections contributed more frequently to morbidity in children with entry CD4+ counts of at least 0.20 x 10(9)/L (together over five times as frequent) than did serious bacterial infection, the primary outcome measure of the trial. Opportunistic infections occurred at a similar rate as laboratory-proven serious bacterial infections. In this group of children, IVIG was significantly associated with a decrease in the rate of viral infections and minor bacterial infections per 100 patient-years (36.0 vs 54.0 episodes of viral infection per 100 patient-years, IVIG vs placebo, P = .01; and 115.1 vs 159.7 episodes of minor bacterial infection per 100 patient-years, IVIG vs placebo, P = .02), as well as a decrease in the rate of serious bacterial infections per 100 patient-years (26.4 vs 48.2 episodes per 100 patient-years; P = .002). There was no apparent difference in the rate of opportunistic infections between treatment arms. CONCLUSIONS: Beneficial effect of IVIG was seen across multiple infectious outcome measures, with reductions in serious and minor viral and bacterial infections observed in children with entry CD4+ counts of at least 0.20 x 10(9)/L.

Bacterial Infections↗
PubMedDate not supplied

Reducing the risk of perinatal HIV transmission through zidovudine therapy: treatment recommendations and implications.

In recent years, human immunodeficiency virus (HIV) infection has emerged as a leading cause of death among young children, most of whom acquired their infection perinatally. Without effective prevention efforts, transmission of HIV through heterosexual sex will continue to increase among women, and the number of perinatally infected children will mirror this increase. In 1994, researchers at the National Institutes of Health and its collaborators announced results from a randomized clinical trial indicating that zidovudine therapy administered to a select group of HIV-infected pregnant women and their newborns reduced the risk of perinatal transmission by two-thirds. This article reviews this clinical trial and its significant findings, discusses the ensuing recommendations from the US Public Health Service, discusses their implications for prenatal counseling and testing, and describes future research needs.

Clinical Protocols↗