Cytomegalovirus gastropathy in a child: resolution after ganciclovir therapy.
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Antiviral Agents↗
Biomedical subjects
L M Frenkel
Publications and source records attributed to L M Frenkel.
Oligonucleotide ligation assay for detecting mutations in the human immunodeficiency virus type 1 pol gene that are associated with resistance to zidovudine, didanosine, and lamivudine.
This report describes the detection of mutations in the pol gene of human immunodeficiency virus type 1 associated with resistance to zidovudine, didanosine, and lamivudine by genotyping by an oligonucleotide ligation assay specific codons in the pol gene amplified by PCR. Our studies demonstrate the sensitivity, simplicity, and specificity of this genotyping system.
Anti-HIV Agents↗
Risk of mother-to-infant transmission of HIV-1 is not reduced in CCR5/delta32ccr5 heterozygotes.
To determine if the 32-bp deletion of the chemokine receptor CCR5 (delta32ccr5) protects against mother-to-infant transmission of HIV-1, specimens from all uninfected and infected children who were perinatally exposed to HIV-1 and observed since 1988 and whose mothers did not take zidovudine were assessed for delta32ccr5. The CCR5 genotype was determined using polymerase chain reaction (PCR) for 122 subjects, of whom 73 were HIV-1 infected and 49 were perinatally exposed but uninfected; 70% and 71%, respectively, were Caucasian. Eleven of 73 (15%) infected children and 4 of 49 (8%) exposed uninfected children were CCR5/delta32ccr5 heterozygotes (p = 0.40). Among subjects who had at least one Caucasian parent or grandparent, 11 of 51 (22%) HIV-1-infected persons and 4 of 35 (11%) uninfected persons were heterozygotes. None were homozygous for the delta32ccr5 allele. The estimated relative risk for mother-to-infant HIV-1 transmission in heterozygotes was 2.0. Furthermore, the 95% confidence interval (0.6, 7.3) suggested that it is unlikely that the true relative risk was <0.6. Thus, the infant CCR5/delta32ccr5 heterozygous genotype was not associated with a diminished risk of perinatally acquired HIV-1 infection.
Alleles↗
Issues regarding antiretroviral treatment for patients with HIV-1 infection.
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Adult↗
Effect of pregnancy and zidovudine therapy on viral load in HIV-1-infected women.
The objective of this study was to determine the effect of pregnancy and zidovudine (ZDV) on viral load in HIV-1 infected women. A prospective nonrandomized cohort study was conducted at a university medical center and affiliated clinic and included 44 HIV-1-seropositive pregnant women seen between June 1991 and September 1995. Twenty-three women initiated ZDV therapy during their pregnancy. Seventeen women did not take antiretrovirals, and four women took ZDV prior to and throughout pregnancy. HIV-1 viral load as determined by quantitative peripheral blood mononuclear cell (PBMC) culture and quantitative plasma RNA levels was measured at various times during pregnancy and in the postpartum period. HIV-1 load, by both infectivity and RNA levels, was relatively low and remained stable during pregnancy and through 6 weeks post partum. Initiation of ZDV therapy during pregnancy did not result in a significant decrease in viral load at delivery when controlling for the effect of pregnancy. In those women who received ZDV therapy only during pregnancy, there was a trend toward an increase in viral load measured by PBMC infectivity 6 months post partum compared with the levels before the initiation of ZDV. Mother-to-child transmission of HIV-1 occurred in one of 27 (4%) ZDV-treated women and in two of 16 (12.5%) untreated women. Among HIV-1-infected pregnant women with low viral levels, HIV-1 plasma RNA and infectivity remained stable during and after gestation. Although these results are based on a relatively small number of women and should be considered preliminary, the lack of significant ZDV-associated diminution in viral levels suggests that the protective effect of ZDV on the mother-to-child transmission of HIV-1 may not be due to the reduction in maternal viral levels but, by inference, may be due to the prevention of HIV-1 reverse transcription in the newborn.
Anti-HIV Agents↗
Lack of detection of human immunodeficiency virus type 1 in the saliva of infected children and adolescents.
OBJECTIVE: To determine the prevalence of human immunodeficiency virus type 1 (HIV-1) in the saliva of infected children and adolescents. METHODS: Saliva and blood samples were collected from 13 patients (age range, 1-15 years) with HIV-1 infection. Eleven were taking antiretroviral agents. The presence of HIV-1 was determined by polymerase chain reaction analysis of RNA and DNA as well as by viral culture of the saliva samples and by culture of peripheral blood mononuclear cells. RESULTS: Although HIV-1 was cultured from peripheral blood mononuclear cells of 12 patients, it was not cultured from their saliva. Only 1 of 13 saliva samples yielded positive test results for HIV-1 RNA, and none did so for HIV-1 DNA. The specimen containing HIV-1 RNA was from an untreated 10-year-old asymptomatic boy with a CD4+ lymphocyte count of 0.91 x 10(9)/L (913 cells/microL) and no infectious virus detected in plasma. CONCLUSION: The prevalence of HIV-1 in the saliva of HIV-1-infected children and adolescents is low and may not be infectious.
Adolescent↗
Pediatric HIV-1 infection.
Although there is optimism that with the prospective identification and treatment of HIV-1-infected pregnant women the incidence of pediatric infection can be diminished, currently the number of HIV-1-infected children continues to rise. Improvements in early diagnosis provide the potential for early intervention, and the advent of more potent antiretroviral agents provides the hope of better treatment strategies to slow disease progression in HIV-1-infected children.
AIDS-Related Opportunistic Infections↗
Prevention of mother-to-infant transmission of HIV-1.
The number of children with AIDS continues to increase worldwide. Children who become infected with HIV-1 acquire the infection almost exclusively from their mothers during pregnancy or delivery, or via breast feeding. Mother-to-infant transmission has been, and continues to be, an area of active research with the goal being complete prevention. Treatment with zidovudine, an antiviral agent, has been found to decrease transmission from 25% to 8%. However, multiple obstacles impede the worldwide application of this advance.
Acquired Immunodeficiency Syndrome↗
Analysis of the maternal components of the AIDS clinical trial group 076 zidovudine regimen in the prevention of mother-to-infant transmission of human immunodeficiency virus type 1.
To gain insight into the protective effects of the three components of the zidovudine regimen used in AIDS Clinical Trial Group (ACTG) 076 on mother-to-infant transmission of human immunodeficiency virus (HIV) type 1, 188 zidovudine-treated women and their untreated infants from five HIV-1 obstetric centers were retrospectively studied. The overall rate of mother-to-infant transmission was 12.3% (95% confidence interval [CI], 7.9%-18.0%). When the 38 women with <200 CD4 cells/microL were excluded, the mother-to-infant transmission rate was 8.8% (95% CI, 4.6%-14.8%). This rate compares favorably with the 8.3% transmission in the zidovudine arm of the ACTG 076 study. Apart from low (<200/microL) maternal CD4 cells (P = .016), no factors, including the duration of zidovudine therapy during gestation and intravenous administration of zidovudine during labor, affected the rate of mother-to-infant transmission. These findings suggest that antenatal oral zidovudine may be as effective as antenatal oral plus intravenous zidovudine during labor and the three-component ACTG 076 regimen in decreasing mother-to-infant HIV-1 transmission.
Acquired Immunodeficiency Syndrome↗
Clinical, virologic and immunologic responses of children with advanced human immunodeficiency virus type 1 disease treated with protease inhibitors.
OBJECTIVE: To determine the effects of combination antiretroviral therapy including a protease inhibitor (PI combination therapy) in children with advanced HIV-1 disease. STUDY DESIGN: An observational study of HIV-1 plasma RNA, lymphocyte subsets, delayed type hypersensitivity and physical growth after initiation of PI combination therapy. RESULTS: In nine children the median HIV-1 plasma RNA decreased 1.7 log10 (mean, 1.57; range, 0.7 to 2.2) following PI combination therapy and CD4 cells increased a median of 499 (mean, 528; range, 9 to 1088) cells/microl. A rebound of RNA, associated with the development of resistance to the PI, occurred in three subjects. Three of six children were no longer anergic and all nine achieved normal weight-growth velocities. Ritonavir was well-tolerated, despite its bitter taste; however, four of five children treated with indinavir developed renal complications. CONCLUSIONS: PI combination therapy in children with advanced HIV-1 disease was associated with a decrease in HIV-1 RNA, improved immunologic measures and normal or better weight gain. Of concern was the rebound in plasma HIV-1 associated with resistance to the PI observed in one-third of patients. This emphasizes the need for larger studies to define optimal PI containing regimens with long term efficacy in children.
Adolescent↗
A search for persistent rubella virus infection in persons with chronic symptoms after rubella and rubella immunization and in patients with juvenile rheumatoid arthritis.
Peripheral blood polymorphonuclear leukocytes, mononuclear cells, and plasma and nasopharyngeal specimens were obtained from 6 subjects with persistent symptoms following rubella immunization, 1 subject with persistent symptoms following rubella, 11 children with juvenile rheumatoid arthritis, 17 recently immunized control subjects, and 1 control subject with acute clinical rubella. Rubella virus was isolated from the blood or nasopharynx of four of the 18 control subjects. In contrast, rubella virus was not recovered from any specimens from the seven subjects with persistent symptoms following immunization or natural infection or from the 11 children with juvenile rheumatoid arthritis. A polymerase chain reaction assay detected rubella virus in the blood from three of 14 control subjects but not in the blood from two subjects with persistent symptoms following rubella immunization or in that from three children with juvenile rheumatoid arthritis. We have not been able to confirm the findings of others who have reportedly recovered rubella virus from lymphocytes of persons with persistent symptoms following rubella or rubella immunization.
Adolescent↗
Interlaboratory comparison of sequence-specific PCR and ligase detection reaction to detect a human immunodeficiency virus type 1 drug resistance mutation. The AIDS Clinical Trials Group Virology Committee Drug Resistance Working Group.
Sequence-specific PCR was used in six laboratories and a ligase detection reaction was used in one laboratory to detect the zidovudine-resistance mutation at codon 215 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase DNA. The genotypes of 27 different clinical samples, including cultured HIV-1 isolates, peripheral blood mononuclear cells, and plasma, were correctly identified by 140 of 154 (91%) assays. The sensitivity for detecting a mutation was 96% for HIV-1 reverse transcriptase DNA clone mixtures containing 30% mutant DNA and 62% for mixtures containing 6% mutant DNA.
Antiviral Agents↗
Effects of zidovudine use during pregnancy on resistance and vertical transmission of human immunodeficiency virus type 1.
The resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine and the vertical transmission of the virus were assessed among all 62 HIV-1-infected pregnant women identified prior to delivery at one institution. HIV-1 was transmitted to infants from 11 (26%) of 42 women who did not receive oral zidovudine but from only 1 of 20 women given such treatment (P = .04). Isolates of HIV-1 from 16 of the 20 zidovudine-treated women were available. Twelve of 16 isolates were wild-type for pol codons 41, 67, 70, 215, and 219; two (one susceptible and one moderately resistant to zidovudine) had mutations at codon 70; and two (both highly resistant to zidovudine) had mutations at codons 41 and 215. The virus was vertically transmitted from a woman infected with one of the highly resistant strains, and the infant's isolate was highly resistant to zidovudine. These limited data suggest that maternal treatment with oral zidovudine reduces the rate of vertical transmission of HIV-1 but that vertical transmission of virus resistant to zidovudine can occur.
Acquired Immunodeficiency Syndrome↗
Correlation of clinical progression in human immunodeficiency virus-infected children with in vitro zidovudine resistance measured by a direct quantitative peripheral blood lymphocyte assay.
A rapid method for determination of zidovudine resistance was developed and results were correlated with clinical outcome in human immunodeficiency virus (HIV)-infected children. The zidovudine susceptibilities of HIV-1 isolates from 34 children were determined through a direct quantitative peripheral blood lymphocyte assay and compared with results of the AIDS Clinical Trials Group resistance assay. Patients' peripheral blood lymphocytes were 5-fold diluted and cocultured with donor lymphocytes and varying concentrations of zidovudine. Isolates were defined as sensitive if inhibited by < or = 1.0 microM zidovudine and resistant at > 1.0 microM. Children (n = 21) with zidovudine-resistant virus had greater evidence of disease progression than did those with zidovudine-sensitive virus (n = 11) as demonstrated by failure to thrive (57% vs. 9%, P = .01) and opportunistic infections (48% vs. 0, P = .006). This assay may be useful as a screening tool for development of clinically relevant zidovudine resistance.
Child↗
Specific, sensitive, and rapid assay for human immunodeficiency virus type 1 pol mutations associated with resistance to zidovudine and didanosine.
The effectiveness of antiretroviral therapy may be limited by the development of human immunodeficiency virus type 1 (HIV-1) resistance. Monitoring for resistance will perhaps allow changes in therapy prior to deterioration in the patient's clinical or immunologic status. Our objective was to develop a rapid, specific, and sensitive genotypic assay for HIV-1 resistance to zidovudine (ZDV) and didanosine (ddI) which is simple to perform. In our assay the DNA of HIV-1 pol was amplified by PCR using two sets of nested oligonucleotide primers. Mutations of reverse transcriptase (RT) encoding amino acids (aa) 74 and 41, 70, and 215 which have been associated with HIV-1 resistance to ddI and ZDV, respectively, were detected with a ligase detection reaction (LDR) and indicated colorimetrically. The RT genotypes of 35 patient specimens (140 codons) blindly assessed for these mutations were in agreement by PCR-LDR and by dideoxynucleotide sequencing. To evaluate the limits of the assay, other specimens with mutations close to the ligation site were evaluated by PCR-LDR. The assay was sensitive and specific for all specimens except when mutations occurred within 2 bases on either side of the ligation site. In summary, this PCR-LDR assay specifically, sensitively, and rapidly detected pol mutations (RT aa 74, 41, 70, and 215) associated with HIV-1 resistance to ddI and ZDV.
Base Sequence↗
The in vitro growth and serial passage of RA 27/3 rubella vaccine virus in cord blood mononuclear leukocytes from normal babies.
Because of our inability to isolate rubella virus from peripheral blood lymphocytes from patients with chronic symptoms after rubella immunization we performed a series of experiments with cord blood mononuclear cells (CBL) to determine whether and to what extent these cells supported the growth of rubella virus in vitro. CBL were stimulated with phytohemagglutinin for 48-72 h, washed, and inoculated with 1000 tissue culture 50% infection dose of rubella virus and placed in RPMI 1640 medium with 10% fetal bovine serum and IL-2. Approximately every 9 d the volume was halved, and new CBL were added. Aliquots at 2- to 9-d intervals were obtained and quantitatively cultured in African green monkey tissue culture. Rubella virus growth was determined by echovirus 11 challenge. Controls consisted of rubella virus in RPMI 1640 medium. Rubella virus persisted in CBL culture longer than in control medium in seven of 11 experiments, and in three instances there was evidence of productive infection.
Animals↗
A search for persistent measles, mumps, and rubella vaccine virus in children with human immunodeficiency virus type 1 infection.
OBJECTIVE: To determine whether live measles, mumps, and rubella vaccine viruses persist after immunization of immunocompromised children with human immunodeficiency virus type 1 infection. METHODS: Ten children with symptomatic human immunodeficiency virus type 1 infection who received measles, mumps, and rubella immunizations were studied. Peripheral blood mononuclear cells, polymorphonuclear leukocytes, and plasma were cocultivated with primary African green monkey kidney tissue culture cells for detection of measles, mumps, and rubella viruses. Antibody to measles and mumps was determined by indirect fluorescent antibody and rubella was determined by enzyme-linked immunosorbent assay. Children seronegative to measles were revaccinated. RESULTS: Neither measles, mumps, nor rubella virus was recovered from peripheral blood mononuclear cells, polymorphonuclear leukocytes, or plasma in these children. No child experienced symptoms thought to be related to the vaccines. Humoral immunity after one or two immunizations was detected in 33% of the children. After vaccination, two of 10 children had IgG to measles; four of 10, to mumps; and four of 10, to rubella. CONCLUSIONS: In spite of an impaired humoral immune response, persistent viremia or infection did not occur after immunization with attenuated measles, mumps, and rubella vaccine viruses. These findings suggest that immunologic response to these viruses was sufficient to prevent persistent infection in these children immunocompromised by human immunodeficiency virus type 1 infection.
Acquired Immunodeficiency Syndrome↗
Clinical reactivation of herpes simplex virus type 2 infection in seropositive pregnant women with no history of genital herpes.
OBJECTIVE: To determine the risk for genital herpes and asymptomatic herpes simplex virus (HSV) shedding in late pregnancy and delivery in a population of HSV type 2 (HSV-2)-seropositive but previously asymptomatic pregnant women. DESIGN: A prospective inception cohort study. PARTICIPANTS: A total of 1355 pregnant women with no history of genital herpes referred from three private obstetrics practices between November 1985 and June 1988. MAIN OUTCOME MEASURES: Confidential questionnaires evaluated sexual risk factors in relation to HSV-2 serologic status as determined by Western blot analysis. Herpes simplex virus shedding was determined by viral culture of the cervix and vulva and of any suspicious lesions. RESULTS: Antibody to HSV-2 was detected in 439 of 1355 pregnant women (32%) with no history of genital herpes. Asymptomatic HSV shedding was detected in 5 of 1160 cultures (0.43%) obtained in late pregnancy and during delivery. A first episode of clinical genital herpes was recognized by 43 of 264 HSV-2-seropositive women (16%) during their pregnancy. CONCLUSIONS: Serologic evidence of unknown HSV-2 infection was common in pregnant women without a history of genital herpes. Asymptomatic viral shedding in these women occurred at a rate similar to that seen in women with symptomatic genital HSV-2 infection. To improve recognition of genital herpes near term, obstetricians should counsel pregnant women about the high prevalence and mild and diverse symptoms of genital HSV-2 infection.
Adult↗