Author
Alice Stek
Other affiliations: National Institutes of Health, University of Cincinnati Academic Health Center, Boston Medical Center ...read more
Bio: Alice Stek is an academic researcher from University of Southern California. The author has contributed to research in topics: Pregnancy & Postpartum period. The author has an hindex of 34, co-authored 79 publications receiving 4001 citations. Previous affiliations of Alice Stek include National Institutes of Health & University of Cincinnati Academic Health Center.
Papers published on a yearly basis
Papers
More filters
TL;DR: In this article, the authors performed a meta-analysis to evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), using data on individual patients from 15 prospective cohort studies.
Abstract: Background To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. Methods North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. Results The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19). Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. Conclusions The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine.
630 citations
TL;DR: As compared with no antiretroviral therapy or monotherapy, combination therapy for HIV-1 infection in pregnant women is not associated with increased rates of premature delivery or with low birth weight, low Apgar scores, or stillbirth in their infants.
Abstract: Background Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. Methods We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. Results After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (<37 weeks of gestation) was similar among the women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (<2500 g) was 16 percent among the i...
377 citations
TL;DR: LPV/r exposure during late pregnancy was lower compared to postpartum and compared to non-pregnant historical controls, and the pharmacokinetics, safety, and effectiveness of increased LPV/ r dosing during the third trimester of pregnancy should be investigated.
Abstract: Background Optimal antiretroviral exposure during pregnancy is critical for prevention of mother-to-child HIV transmission and for maternal health. Pregnancy can alter antiretroviral pharmacokinetics. Our objective was to describe lopinavir/ritonavir (LPV/r) pharmacokinetics during pregnancy. Methods We performed intensive steady-state 12-h pharmacokinetic profiles of lopinavir and ritonavir (three capsules: LPV 400 mg/r 100 mg) at 30-36 weeks gestation and 6-12 weeks postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured LPV and ritonavir by reverse-phase high-performance liquid chromatography. Target LPV area under concentration versus time curve (AUC) was > or = 52 microg h/ml, the estimated 10th percentile LPV AUC in non-pregnant historical controls (mean AUC = 83 microg h/ml). Results Seventeen women completed antepartum evaluations; average gestational age was 35 weeks. Geometric mean antepartum LPV AUC was 44.4 microg h/ml [90% confidence interval (CI), 38.7-50.9] and 12-h post-dose concentration (C12h) was 1.6 microg/ml (90% CI, 1.1-2.5). Twelve women completed postpartum evaluations; geometric mean LPV AUC was 65.2 microg h/ml (90% CI, 49.7-85.4) and C12h was 4.6 microg/ml (90% CI, 3.7-5.7). The geometric mean ratio of antepartum/postpartum LPV AUC was 0.72 (90% CI, 0.54-0.96). Fourteen of 17 (82%) pregnant and three of 12 (25%) postpartum women did not meet our target LPV AUC. The ratio of cord blood/maternal LPV concentration in ten paired detectable samples was 0.2 +/- 0.13. Conclusions LPV/r exposure during late pregnancy was lower compared to postpartum and compared to non-pregnant historical controls. Small amounts of lopinavir cross the placenta. The pharmacokinetics, safety, and effectiveness of increased LPV/r dosing during the third trimester of pregnancy should be investigated.
184 citations
TL;DR: Continuous nevirapine may be associated with increased toxicity among HIV-1-infected pregnant women with CD4 cell counts greater than 250 cells/μL, as has been observed in non-pregnant women.
Abstract: Objective To compare the safety of nelfinavir and nevirapine-based antiretroviral treatment in HIV-1-infected pregnant women. Methods In Pediatric AIDS Clinical Trials Group Protocol 1022, 38 antiretroviral-naive pregnant women at 10-30 weeks' gestation were randomized to nelfinavir or nevirapine with zidovudine plus lamivudine. The study was suspended because of greater than expected toxicity and changes in nevirapine prescribing information. The incidence of treatment-limiting hepatic or cutaneous toxicity was compared between groups for all subjects and for the subset with CD4 cell counts greater than 250 cells/microL at study entry. Results Toxicity was seen in 1 (5%) of 21 subjects randomized to nelfinavir and 5 (29%) of 17 subjects randomized to nevirapine (P = 0.07). Within the nevirapine group, 1 subject developed fulminant hepatic failure and died, and another developed Stevens-Johnson syndrome. The one adverse event associated with nelfinavir occurred in a subject with a CD4 cell count less than 250 cells/microL. All 5 events among subjects with a CD4 cell count greater than 250 cells/microL were associated with nevirapine (P = 0.04). Conclusions Continuous nevirapine may be associated with increased toxicity among HIV-1-infected pregnant women with CD4 cell counts greater than 250 cells/microL, as has been observed in non-pregnant women.
159 citations
TL;DR: The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidvudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.
Abstract: Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts ≤500/ μL (22% had counts <200/μL) and required zidovudine for maternal health (24% received zidovudine before pregnancy). Transmission was associated with lower maternal baseline CD4 cell count (odds ratio, 1.58 per 100-cell decrement; P =.005; 10.0% vs. 3.6% transmission for count <200 vs. ≥200/μL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P =.75). The Kaplan-Meier transmission rate for HIVIG recipients was 4.1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P =.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.
153 citations
Cited by
More filters
Journal Article•
TL;DR: The objectives of these recommendations are to increase HIV screening of patients, including pregnant women, in health-care settings; foster earlier detection of HIV infection; identify and counsel persons with unrecognized HIV infection and link them to clinical and prevention services; and further reduce perinatal transmission of HIV in the United States.
Abstract: These recommendations for human immunodeficiency virus (HIV) testing are intended for all health-care providers in the public and private sectors, including those working in hospital emergency departments, urgent care clinics, inpatient services, substance abuse treatment clinics, public health clinics, community clinics, correctional health-care facilities, and primary care settings. The recommendations address HIV testing in health-care settings only. They do not modify existing guidelines concerning HIV counseling, testing, and referral for persons at high risk for HIV who seek or receive HIV testing in nonclinical settings (e.g., community-based organizations, outreach settings, or mobile vans). The objectives of these recommendations are to increase HIV screening of patients, including pregnant women, in health-care settings; foster earlier detection of HIV infection; identify and counsel persons with unrecognized HIV infection and link them to clinical and prevention services; and further reduce perinatal transmission of HIV in the United States. These revised recommendations update previous recommendations for HIV testing in health-care settings and for screening of pregnant women (CDC. Recommendations for HIV testing services for inpatients and outpatients in acute-care hospital settings. MMWR 1993;42[No. RR-2]:1-10; CDC. Revised guidelines for HIV counseling, testing, and referral. MMWR 2001;50[No. RR-19]:1-62; and CDC. Revised recommendations for HIV screening of pregnant women. MMWR 2001;50[No. RR-19]:63-85). Major revisions from previously published guidelines are as follows: For patients in all health-care settings HIV screening is recommended for patients in all health-care settings after the patient is notified that testing will be performed unless the patient declines (opt-out screening). Persons at high risk for HIV infection should be screened for HIV at least annually. Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing. Prevention counseling should not be required with HIV diagnostic testing or as part of HIV screening programs in health-care settings. For pregnant women HIV screening should be included in the routine panel of prenatal screening tests for all pregnant women. HIV screening is recommended after the patient is notified that testing will be performed unless the patient declines (opt-out screening). Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing. Repeat screening in the third trimester is recommended in certain jurisdictions with elevated rates of HIV infection among pregnant women.
2,958 citations
University of Zurich1, Icahn School of Medicine at Mount Sinai2, University of North Carolina at Chapel Hill3, Monash University4, University Hospital of Lausanne5, University of California, San Diego6, Radboud University Nijmegen7, University of Buenos Aires8, Cornell University9, University of Amsterdam10, University of Alabama at Birmingham11, Johns Hopkins University School of Medicine12, University of California, San Francisco13
TL;DR: This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient monitoring, when to change therapy, and what regimens to use when changing.
Abstract: Context New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–infected adults in resource-rich settings. Objective To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. Data Sources, Study Selection, and Data Extraction Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society–USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. Data Synthesis Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. Conclusion New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.
2,357 citations
01 Jan 2006
TL;DR: These guidelines are primarily intended for use by national and regional HIV programme managers managers of nongovernmental organizations delivering HIV care services and other policy-makers who are involved in the scaling up of comprehensive HIV care and ART in resource-limited countries.
Abstract: This publication is intended to serve as a reference tool for countries with limited resources as they develop or revise national guidelines for the use of ART in adults and postpubertal adolescents (see Annex 9 for pubertal Tanner staging; prepubertal adolescents should follow the WHO paediatric guidelines). The material presented takes updated evidence into account including new ART treatment options and draws on the experience of established ART scale-up programmes. The simplified approach with evidence-based standards continues to be the basis of WHO recommendations for the initiation and monitoring of ART. The guidelines are primarily intended for use by national and regional HIV programme managers managers of nongovernmental organizations delivering HIV care services and other policy-makers who are involved in the scaling up of comprehensive HIV care and ART in resource-limited countries. The comprehensive up-to-date technical and clinical information on the use of ART however also makes these guidelines useful for clinicians in resource-limited settings. The recommendations contained in these guidelines are made on the basis of different levels of evidence from randomized clinical trials high-quality scientific studies observational cohort data and where insufficient evidence is available expert opinion. The strengths of the recommendations in Table 1 are intended to indicate the degrees to which the recommendations should be considered by regional and country programmes. Cost-effectiveness is not explicitly considered as part of the recommendations although the realities of human resources health system infrastructures and socioeconomic issues should be taken into account when the recommendations are being adapted to regional and country programmes. (excerpt)
1,454 citations
TL;DR: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission and the protective effect of therapy increased with the complexity and duration of the regimen.
Abstract: Context The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. Objective To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. Design Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. Main outcome measure HIV-1 status of the infant. Results HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for 30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. Conclusion Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.
872 citations
TL;DR: Neither higher HIV-1 RNA levels early in pregnancy nor higher levels late in pregnancy were associated with the timing of infection in the infants, and in pregnant women with HIV- 1 infection the level of plasma HIV-2 RNA predicts the risk but not the time of transmission of HIV-3 to their infants.
Abstract: Background The importance of plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA in pregnant women in relation to the other factors known to influence the risk of transmission of infection to their infants is incompletely defined. We studied the relation of maternal plasma HIV-1 RNA levels to the risk of perinatal transmission and the timing of transmission. Methods We measured plasma HIV-1 RNA serially in 552 women with HIV-1 infection who had singleton pregnancies. The status of infection in their infants was assessed by culture of blood and further classified as early (if a culture of blood obtained within the first two days of life was positive) or late (if a culture of blood obtained in the first seven days of life was negative but subsequent cultures were positive). The rates of transmission at various levels of maternal plasma HIV-1 RNA were analyzed by tests for trend, with adjustment for covariates by stratification and logistic regression. Results Increasing geometric mean levels of...
789 citations