Systemic pharmacokinetics and cellular pharmacology of zidovudine in human immunodeficiency virus type 1-infected women and newborn infants.

Systemic and intracellular pharmacokinetics of zidovudine were determined for 28 human immunodeficiency virus type 1-infected pregnant women and their newborn infants. Plasma zidovudine and intracellular zidovudine monophosphate and triphosphate concentrations were determined in serial maternal samples and cord blood at delivery. Higher levels of cord blood zidovudine were associated with lower maternal zidovudine clearance and longer infusion times. Median levels of zidovudine monophosphate and triphosphate in maternal (1556 and 67 fmol/106 cells) and cord (1464 and 70 fmol/106 cells) blood were similar but highly variable. Intersubject pharmacokinetic variability for zidovudine is substantial, but intravenous therapy provides plasma concentrations and intracellular zidovudine triphosphate levels consistent with high antiviral activity. The substantial amount of intracellular zidovudine triphosphate in cord blood provides an explanation for the clinical success of zidovudine in reducing vertical transmission. Studies of simpler oral regimens of zidovudine can now be evaluated regarding the ability to achieve these pharmacologic end points associated with highly effective parenteral therapy.

Effect of human immunodeficiency virus infection on serum beta2-microglobulin levels in pregnant women.

OBJECTIVE: To assess serum beta2-microglobulin levels in human immunodeficiency virus (HIV)-infected and uninfected pregnant women, variations of serum beta2-microglobulin levels during pregnancy and postpartum, factors that might influence beta2-microglobulin levels in pregnant women, and the association between beta2-microglobulin and perinatal HIV-1 transmission. METHODS: We assayed 374 stored (-70C) serum samples from pregnant women enrolled in the Newark perinatal HIV-1-transmission study and 18 nonpregnant women for beta2-microglobulin using a microparticulate enzyme immunoassay. The Student t test, Wilcoxon rank test, binomial test, and Spearman correlation coefficient were used for statistical analysis, with P < .05 considered statistically significant. A linear regression model was used to assess the effect of independent variables on serum beta2-microglobulin levels. RESULTS: There were no significant differences (P = .16) in serum beta2-microglobulin levels between pregnant and nonpregnant HIV-negative women (1.07+/-0.35 versus 0.99+/-0.18 mg/L). Beta2-Microglobulin levels did not vary throughout pregnancy and postpartum, irrespective of HIV serostatus. Substance abuse did not alter beta2-microglobulin levels. Human immunodeficiency virus infection caused significant increases of this surrogate marker, but it could not discriminate among disease stages. Beta2-Microglobulin levels at delivery were lower among women who delivered HIV-infected infants. CONCLUSION: Human immunodeficiency virus infection was associated with increased serum beta2-microglobulin levels in pregnant women and was the most significant correlate of increases of that marker. Pregnancy and substance use during pregnancy did not influence levels of serum beta2-microglobulin significantly.

Pharmacokinetics of didanosine in antepartum and postpartum human immunodeficiency virus--infected pregnant women and their neonates: an AIDS clinical trials group study.

Didanosine (ddI) pharmacokinetics in antepartum and postpartum human immunodeficiency virus (HIV)-infected women and their neonates were studied. HIV-infected pregnant women received an intravenous (iv) ddI infusion (1.6 mg/kg/h) or an oral dose (200 mg bid or 125 mg bid) at 31 weeks antepartum and 6 weeks postpartum. Blood samples were obtained regularly up to 6 or 8 h after drug administration. The same oral dose of ddI (bid) was administered until labor began. Then, ddI was infused iv until delivery. An oral pharmacokinetic study (60 mg/m2) was conducted in infants at day 1 and at week 6 after birth. Plasma concentrations of ddI were measured by radioimmunoassay. After iv ddI administration, only the maternal plasma clearance was found to be significantly increased antepartum (1028+/-231 mL/min) versus postpartum (707+/-213 mL/min). No pharmacokinetic parameters after oral administration were significantly affected by pregnancy. The pharmacokinetics of ddI in the neonates were highly variable. We conclude that the oral ddI dose need not be adjusted during pregnancy.

Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV. Perinatal AIDS Collaborative Transmission Studies.

OBJECTIVES: To evaluate the impact of perinatal zidovudine use on the risk of perinatal transmission of HIV and to determine risk factors for transmission among women using perinatal zidovudine. DESIGN: Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities. METHODS: The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics. RESULTS: The overall transmission risk was 18% [95% confidence interval (CI), 16-21]. Factors associated with transmission included membrane rupture > 4 h before delivery [relative risk (RR), 2.1; 95% CI, 1.6-2.7], gestational age < 37 weeks (RR, 1.8; 95% CI, 1.4-2.2), maternal CD4+ lymphocyte count < 500 x 10(6) cells/l (RR, 1.7; 95% CI, 1.3-2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3-2.1), and antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4-0.9). For infants exposed to zidovudine antenatally and neonatally, the transmission risk was 13% overall but was significantly lower following shorter duration of membrane rupture (7%) and term delivery (9%). The transmission risk declined from 22% before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine use and changes in other risk factors. CONCLUSIONS: Perinatal HIV transmission risk has declined with increasing perinatal zidovudine use and changes in other factors. Further reduction in transmission for women taking zidovudine may be possible by reducing the incidence of other potentially modifiable risk factors, such as long duration of membrane rupture and prematurity.

Lymphocyte shedding from genital tract of human immunodeficiency virus-infected women: immunophenotypic and clinical correlates.

OBJECTIVE: Our purpose was to describe the lymphocyte subpopulations in genital tract samples from human immunodeficiency virus-infected women and the clinical correlates associated with lymphocyte shedding. STUDY DESIGN: Genital tract samples of women infected with human immunodeficiency virus-1 were processed for immunophenotyping analysis with a FACScan flow cytometer. Immunologic and virologic characteristics of women with and without lymphocyte shedding were compared with t test, Wilcoxon rank test, or Fisher's exact test. RESULTS: The rate of genital lymphocyte shedding among human immunodeficiency virus-1-infected women was 39%. Genital shedding was not related to age, race, use of antiretroviral therapy, or positive human immunodeficiency virus-1 culture. A negative rank correlation (r = -0.71, p = 0.047) between CD3+ CD4+ counts in peripheral blood and genital tract was observed. The majority of the lymphocyte cells were CD3+ CD8+, and > 80% of the CD3+ CD4+ cells were memory cells. CONCLUSION: The immune profile of the genital tract lymphocytes is suggestive of a local mucosal immune response.

Human immunodeficiency virus type 1 counseling and testing program in the prenatal setting.

OBJECTIVE: The objectives of this study were to ascertain the acceptance rate of human immunodeficiency virus type 1 (HIV-1) testing in a high-prevalence area and to describe the sociodemographic and clinical characteristics of seropositive women diagnosed in the prenatal setting. METHODS: A retrospective review was carried out of the prenatal HIV-1 counseling and testing program at University Hospital, Newark, NJ (1989-1990). RESULTS: Sixty-seven percent (741/1,114) of the women offered HIV-1 counseling services accepted testing and 40 (40/741:5.3%) new cases were identified. Heterosexual contact was the primary exposure (17:52%) of these women, of whom 13 (73%) had negative syphilis serologies. Sixty-four percent were asymptomatic. The mean absolute CD4 lymphocyte count in seropositive women was 514 +/- 305 cells/mm(3) . Severe immunosuppression was seen in 7/32 (22%) patients. Seventy-three percent (24/33) depended on public-assistance programs for their health-care services. CONCLUSIONS: A voluntary HIV-1 counseling and testing program is well accepted in the prenatal setting. It can provide early identification of asymptomatic seropositive women and infants at risk and lead to early intervention and therapy.

Imaging of HIV infection in the prenatal and postnatal period.

Prenatal diagnosis of maternal diseases common to HIV infection may alert the clinician to potential HIV infection in the infant, with resultant early diagnosis and treatment. Although of limited value in the first months of life, imaging studies can be beneficial in selected cases and may be the first clue to the diagnosis of AIDS. The multisystem involvement frequently seen in AIDS necessitates multiple imaging modalities. Recurrent pneumonia, particularly Pneumocystis carinii pneumonia, may be first suggested by the chest radiograph. Brain atrophy and white matter disease, shown on MR imaging or CT early in life, can suggest AIDS. Ultrasonography is not only crucial for prenatal fetal assessment, but it also is important for evaluation of the common findings of hepatomegaly, adenopathy, and tumors, as well as inflammatory fluid collections.

Idiopathic myelofibrosis in pregnancy: a case report and review of the literature.

Idiopathic myelofibrosis is a rare myeloproliferative disorder characterized by excessive accumulation of connective tissue in the bone marrow in association with anemia, splenomegaly, and extramedullary hematopoiesis. The cause of this disease is unknown, and the prognosis is generally poor. To our knowledge, this is the first case report of a patient with idiopathic myelofibrosis who carried a term pregnancy. In spite of the increased perinatal risks, a favorable outcome was possible with close antepartum surveillance.

Cellular immunity in preeclampsia: alterations in T-lymphocyte subpopulations during early pregnancy.

T-lymphocyte subpopulations were evaluated longitudinally in 62 primigravidas. Beginning early in the second trimester, women who later developed preeclampsia showed a significantly lower proportion of T-helper cells compared with those who remained normotensive (27.0 +/- 7.1 versus 34.7 +/- 7.9%; P less than or equal to .001). The decrease in the T-helper cell count occurred several weeks before the development of preeclampsia and reverted to normal 6-10 weeks postpartum.

Multifetal pregnancy in a gonadal dysgenesis mosaic.

A successful triplet gestation in a 45,X/46,XY woman is presented. A previously hypoplastic uterus was prepared for implantation by exogenous hormone replacement. Conception was achieved through in vitro fertilization of donor oocytes and transfer of four embryos into a hormonally primed endometrium. This case illustrates that some women with 45,X/46,XY karyotype can have a successful triplet pregnancy. Therefore, a conservative approach during gonadectomy in patients with a Y chromosome may be warranted.

Nipple stimulation for labor augmentation.

A randomized, prospective study was undertaken to evaluate the efficacy of nipple stimulation with a breast pump as compared to oxytocin for augmentation of labor. The average and maximal uterine activity achieved was significantly higher in the oxytocin-stimulated group, without significant differences in the length of labor stages, cesarean section rate, Apgar scores or umbilical artery pH. Fifty percent of the patients failed to respond to nipple stimulation after 30 minutes and were switched to oxytocin. These patients experienced a more rapid rate of cervical dilation in the active phase and reached higher maximal uterine activity with oxytocin stimulation; however, the cesarean section rate was highest in this group. Nipple stimulation with a breast pump appears to be a safe and effective alternative to oxytocin for the augmentation of labor.