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Biomedical subjects

Geraldo Duarte

Publications and source records attributed to Geraldo Duarte.

At least 19 recordsLinked to original sources

Drug resistance among HIV-infected pregnant women receiving antiretrovirals for prophylaxis.

OBJECTIVE: To quantify primary resistance mutations (PRMs) among HIV-1-infected women receiving antiretroviral therapy (ART) for prevention of mother-to-child transmission (MTCT). METHODS: Peripheral blood mononuclear cell samples from HIV-1-infected women enrolled in a prospective cohort study in Argentina, the Bahamas, Brazil, and Mexico (NISDI Perinatal Study) were assayed for PRMs. Eligible women were those enrolled by March 2005 and diagnosed with HIV-1 infection during the current pregnancy, and who received ART for MTCT prophylaxis and were followed for 6-12 weeks postpartum. RESULTS: Of 819 women, 198 met the eligibility criteria. At enrollment, 98% were asymptomatic, 62% had plasma viral load < 1000 copies/ml, 53% had CD4+ cell count > or = 500 cells/microl, and 78% were ART-exposed (mean duration, 8.0 weeks; 95% confidence interval, 7.1-8.9). The most complex ART regimen during pregnancy was usually (81%) a three-drug regimen [two nucleoside reverse transcriptase inhibitors (NRTIs) + one protease inhibitor or two NRTIs + one non-nucleoside reverse transcriptase inhibitor). PRMs were observed in samples from 19 (16%) of 118 women that were amplifiable at one or both time points [11/76 (14%) at enrollment; 14/97 (14%) at 6-12 weeks]. The occurrence of PRMs was not associated with clinical, immunological, or virological disease stage at either time point, whether ART-naive versus exposed at enrollment, or the most complex or number of antiretroviral drug regimens received during pregnancy (P > 0.1). Of 55 women with amplifiable samples at both time points, PRMs were detected in 11 samples (20%). CONCLUSIONS: PRMs occurred among 16.1% of relatively healthy HIV-1-infected mothers from Latin American and Caribbean countries receiving MTCT prophylaxis.

Adult↗

Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth.

OBJECTIVE: To determine the relationship between maternal antiretroviral regimens during pregnancy and adverse infant outcomes [low birth weight (LBW) and preterm birth]. The a priori hypothesis was that protease inhibitor (PI)-containing regimens are associated with an increased risk of LBW and preterm birth. DESIGN: Prospective cohort study of HIV-1-infected women and their infants (NISDI Perinatal Study). METHODS: Data were analysed from 681 women receiving at least one antiretroviral drug [in order of increasing complexity: one or two nucleoside reverse transcriptase inhibitors (1-2 NRTI), two NRTI plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) (HAART/NNRTI), or two NRTI plus one PI (HAART/PI)] for at least 28 days during pregnancy, and who delivered live born, singleton infants with known birth weight and gestational age by 1 March 2005. Multivariable logistic regression modeling was used to assess the relationship of maternal ART with LBW and with preterm birth, adjusting for covariates. RESULTS: The incidence of LBW and preterm birth, respectively, was 9.6% and 7.4% (1-2 NRTI), 7.4% and 5.8% (HAART/NNRTI), and 16.7% and 10.6% (HAART/PI). There was no statistically significant increased risk of LBW [adjusted odds ratio (AOR), 1.5; 95% confidence interval (95% CI), 0.7-3.2] or preterm birth (AOR, 1.1; 95% CI, 0.5-2.8) among women who received HAART/PI compared with women receiving 1-2 NRTI. CONCLUSIONS: Among a population of HIV-1-infected women in Latin America and the Caribbean, maternal receipt of PI-containing ART regimens during pregnancy was not associated with a statistically significant increase in risk of LBW or preterm birth.

Adult↗

Antiretroviral agents during pregnancy: consequences on hematologic parameters in HIV-exposed, uninfected newborn infant.

OBJECTIVES: To study the effect of antiretroviral drugs administered to pregnant women on hematologic parameters of the neonate. STUDY DESIGN: A prospective cohort study was conducted on 52 neonates divided into three groups: ZDV group, infants born to HIV-infected mothers taking zidovudine (n=18); triple therapy (TT) group, infants born to mothers taking zidovudine+lamivudine+nelfinavir (n=22), and control group, infants born to normal women (n=12). Umbilical cord blood from the newborn infant was used to determine hemoglobin, lymphocyte and platelet. Data were analyzed statistically by the nonparametric tests, with the level of significance set at p<0.05. RESULTS: The major maternal demographic and anthropometric data were homogeneous for the various groups. There was a reduction in hemoglobin levels at birth among TT group newborns (p=0.016). There was no difference between groups regarding gestation length, Apgar scores, platelets or absolute lymphocyte count for the newborn. CONCLUSIONS: An association between the use of combination antiretroviral therapy during pregnancy and reduced neonatal hemoglobin levels was observed, supporting the need for short- and long-term follow-up of infants exposed to antiretroviral drugs during uterine life.

Adolescent↗

Mode of delivery and postpartum morbidity in Latin American and Caribbean countries among women who are infected with human immunodeficiency virus-1: the NICHD International Site Development Initiative (NISDI) Perinatal Study.

OBJECTIVE: The purpose of this study was to test whether cesarean delivery before labor and before ruptured membranes is associated with a higher risk of postpartum morbidity than vaginal delivery among women who are infected with human immunodeficiency virus-1 in Latin America and the Caribbean. STUDY DESIGN: Data from a prospective cohort study (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. The study population consisted of women who were followed for > or = 6 to 12 weeks after delivery, who had singleton infants, and with a known mode of delivery. RESULTS: Of 819 enrollees, 697 women met inclusion criteria (299 vaginal deliveries, 260 cesarean deliveries before labor and before ruptured membranes, 138 cesarean deliveries after labor and/or after ruptured membranes); 36 women (5%) had postpartum morbidity (18 major, 18 minor). Mode of delivery was associated with postpartum morbidity (P = .02). Unadjusted odds ratios (95% CIs) for postpartum morbidity according to mode of delivery were cesarean delivery before labor and before ruptured membranes (odds ratio, 1.16 [95% CI, 0.5, 2.7]), cesarean delivery after labor and/or after ruptured membranes (odds ratio, 2.96 [95% CI, 1.3, 6.7]), and vaginal delivery (reference). These results did not differ appreciably with covariate adjustment. CONCLUSION: The rate of postpartum morbidity was low. Mode of delivery was associated with postpartum morbidity, possibly reflecting the larger proportion of minor postpartum morbidity events among those with cesarean delivery after labor and/or after ruptured membranes.

Adult↗

Group B Streptococcus carriers among HIV-1 infected pregnant women: prevalence and risk factors.

OBJECTIVE: The objective was to determine the frequency and risk factors of anogenital colonization by Streptococcus agalactiae (GBS) in pregnant women infected with human immunodeficiency virus type 1 (HIV-1). STUDY DESIGN: A prospective study was conducted on 207 pregnant women divided into two groups: HIV group (n=101) and a control group consisting of HIV-uninfected pregnant women (n=106) to assess regional colonization by GBS. Anal and vaginal swabs were collected and cultured in Todd-Hewitt broth, followed by a confirmatory test. For a control group with an anticipated proportion based on literature research of 10-30% and alpha=0.05, a sample size of 100 would have a power of 80% to detect a difference of 15% or greater with a study group. The mothers were studied in terms of frequency of anogenital colonization by GBS, maternal epidemiological data, and TCD4 lymphocyte counts. The results were analyzed using the chi(2)-test, Fisher's exact test and the Student's t-test, with the level of significance set at p<0.05. RESULTS: Twenty (19.8%) HIV-1-infected pregnant women were found to be colonized by GBS at between 35 and 37 weeks' gestation. In the control group, the prevalence of GBS was 14.1%. CONCLUSION: No significant increase in GBS colonization was observed in HIV-1-infected pregnant women. Maternal colonization of GBS in HIV-infected pregnant women was not found to be associated with their immunological status. Sexual contact does not seem to be the principal way of transmitting GBS.

Adolescent↗

Analysis of HIV type 1 diversity in pregnant women from four Latin American and Caribbean countries.

Worldwide, the distribution of HIV-1 subtypes and intersubtype recombinants is not homogeneous. In Latin America and the Caribbean, HIV-1 subtype B predominates. However, in the south of Brazil and in countries of the Southern cone (Argentina, Chile, Paraguay, and Uruguay) there is a different distribution of viral subtypes and intersubtype recombinants. The aim of this work was to analyze HIV-1 diversity in a cohort of pregnant women (with primarily heterosexual acquisition of the infection) who were diagnosed with HIV-1 infection during their current pregnancy and who received ARVs during pregnancy for perinatal transmission prophylaxis. Analysis of 121 partial pol sequences from subjects enrolled in Argentina, Brazil, the Bahamas, and Mexico was performed by phylogenetic and recombinant characterization. Different prevalences of subtype B were observed (100% for specimens from Mexico and the Bahamas, 61% for Brazil, and 30% for Argentina). Subtypes C and F were found, along with BC, BF, FC, and CBF recombinants in specimens from Brazilians. A high prevalence of BF recombinants was found (70%) in specimens from Argentina. The different patterns of HIV- 1 subtypes and intersubtype recombinants in South America (Argentina and Brazil) compared to those in Central and North America should be considered in the design of future HIV-1 vaccine trials.

Argentina↗

Ultrasound markers of fetal infection, Part 2: Bacterial, parasitic, and fungal infections.

Up to 1% of all pregnancies have clinically overt intra-amniotic bacterial infections, and an even larger percentage of pregnant women may be affected by silent infections. Although most pregnant women with overt intra-amniotic bacterial infection have experienced prolonged rupture of membranes (PROM), symptomatic and most silent nonviral intra-amniotic infections may occur with intact membranes. The etiology of intra-amniotic infection after PROM is almost always polymicrobial and consists of genital tract pathogens, such as group B streptococci, Chlamydia trachomatis, Neisseria gonorrhoeae, mycoplasmas, aerobic Gram-negative bacilli, such as the coliforms, and facultative and anaerobic endogenous organisms, such as peptococci, peptostreptococci, and Bacteroides species. These organisms gain access to the uterine cavity by the ascending route. Organisms such as Treponema pallidum, Listeria monocytogenes, Toxoplasma gondii, trypanosomes, and plasmodia are capable of gaining access to the amniotic cavity by transplacental hematogenous spread, and cause devastating fetal infections. Symptomatic intra-amniotic infection is usually a diagnosis of exclusion. Diagnostic criteria based on both clinical and laboratory findings lack sensitivity and are nonspecific. It is difficult to obtain uncontaminated intra-amniotic samples, especially when there is PROM. The problem is even greater with silent infections. In most cases, fetal infection is suspected after an unexplained and unexpected adverse outcome. Maternal morbidity is increased with intra-amniotic infection; although maternal mortality is extremely rare in developed countries, this is not the case in societies where pregnant women have limited or no access to medical care. Although infected women who are treated early and aggressively with wide-spectrum antibiotics do well, more than 10% of these women develop bacteremia and up to half of them will require cesarean delivery because of poor uterine contractions and arrest of labor. The overwhelming majority of term neonates exposed to intrauterine infection after PROM do well, but up to 30% of these neonates require treatment of neonatal pneumonia or bacteremia. Outcomes for preterm neonates or for neonates who experienced silent fetal infections are more severe. Morbidity and mortality rates in these cases are high, and survivors may have long-term devastating sequelae. The ability to identify ultrasound markers of fetal infection will help clinicians identify etiologic agents with greater accuracy and correlate these infections with specific antepartum and postpartum syndromes. The recognition of markers of intrauterine infection will also reduce unexpected adverse outcomes that result from undiagnosed fetal infections.

Bacterial Infections↗

Colonization by Streptococcus agalactiae during pregnancy: maternal and perinatal prognosis.

We reviewed colonization by group B Streptococcus beta-haemolyticus of Lancefield (SGB), or Streptococcus agalactiae, in pregnant women, and the consequences of infection for the mother and newborn infant, including factors that influence the risk for anogenital colonization by SGB. We also examined the methods for diagnosis and prophylaxis of SGB to prevent early-onset invasive neonatal bacterial disease. At present, it is justifiable to adopt anal and vaginal SGB culture as part of differentiated obstetrical care in order to reduce early neonatal infection. The rates, risk factors of maternal and neonatal SGB colonization, as well as the incidence of neonatal disease, may vary in different communities and need to be thoroughly evaluated in each country to allow the most appropriate preventive strategy to be selected.

Female↗

Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women.

BACKGROUND: Fentanyl is an opioid drug widely used as a co-adjuvant in abdominal delivery, a fact that justifies its pharmacokinetic study under these conditions. OBJECTIVE: Our objective was to investigate the pharmacokinetics and placental transfer of fentanyl in parturients whose pregnancies were resolved by cesarian section with epidural anesthesia. PATIENTS AND METHODS: Ten clinically normal parturients who delivered at term received 5 ml of 2% lidocaine hydrochloride without a vasoconstrictor for skin and subcutaneous blockade, followed by epidural injection of 2 ml fentanyl citrate (0.05 mg/ml), 15 ml 0.5% bupivacaine hydrochloride with 1:200,000 epinephrine, and 10 ml 2% lidocaine hydrochloride without a vasoconstrictor. Maternal blood samples were collected at various times after injection (1--840 min), and the fentanyl plasma concentrations were determined by gas chromatography-mass spectrometry. Pharmacokinetic analysis was performed using the bi- or tri-compartmental model. The fetal/maternal ratio of the plasma fentanyl was determined at birth. RESULTS: The values of the pharmacokinetic parameters were: t(1/2)alpha=13.5 min, t(1/2)beta=192.5 min, t(1/2)gamma=620 min, AUC(0-infinity)=137.404 ng.min per milliliter, C(l)/f=464.984 ml/min, V(d)/f=299.974 l, C(l)/f/kg=6.875 ml/min per kilogram, and V(d)/f/kg=4.441 l/kg. The latency between drug administration and birth was 28.5 min, with a maternal and fetal plasma concentration of 0.310 and 0.245 ng/ml, respectively, at a median fetal/maternal ratio of 0.892. CONCLUSION: The study demonstrated a rapid passage of fentanyl from the epidural space to maternal blood and a significant transplacental transfer of maternal fentanyl of about 90%, which should serve as an alert to obstetricians.

Analgesia, Epidural↗

Effect of antiretroviral drugs on maternal CD4 lymphocyte counts, HIV-1 RNA levels, and anthropometric parameters of their neonates.

PURPOSE: To study the effect of antiretroviral drugs administered during pregnancy on CD4 lymphocyte counts and HIV-1 RNA levels of pregnant women and on the anthropometric parameters of their neonates. METHODS: A prospective study was conducted on 57 pregnant women and their neonates divided into 3 groups: ZDV Group, HIV-infected mothers taking zidovudine (n=20); triple therapy (TT) Group, mothers taking zidovudine+lamivudine+nelfinavir (n=25), and Control Group, normal women (n=12). CD4 lymphocyte counts and HIV-1 RNA levels of pregnant women were analyzed during two periods of pregnancy. The perinatal prognosis took into account preterm rates, birth weight, intrauterine growth restriction, perinatal death, and vertical transmission of HIV-1. Data were analyzed statistically using the nonparametric chi-square, Mann-Whitney, Friedman, Kruskal-Wallis, and Wilcoxon matched pairs tests, with the level of significance set at P<.05. RESULTS: The major maternal demographic and anthropometric data were homogeneous for the various groups. HIV-1 viral burden, which was initially elevated, median of 14,370 copies/mL, was significantly reduced in the TT group, reaching 40 copies/mL. With respect to T-CD4+ lymphocyte counts, there was a significant recovery in Group TT at the end of pregnancy, this value being significantly different from that for the ZDV group (P=0052). There was no difference between groups regarding gestation length, Apgar scores, or neonatal anthropometric classification. There was no case of vertical HIV-1 transmission. CONCLUSIONS: The results obtained for the present series demonstrate the efficiency and suggest safety of the use of antiretroviral drugs during pregnancy as revealed by anthropometric parameters of the neonate.

Adolescent↗

HPV16, HPV18, and HIV infection may influence cervical cytokine intralesional levels.

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk to cervical cancer. This study analyzed the influence of HPV infection on cytokine intralesional levels in cervical lesion in the presence or not of HIV infection. Cervical biopsies from 42 women were studied. HPV detection and typing were performed using amplified DNA hybridized with sequence-specific primers, and cytokine intralesional levels were detected using ELISA. HPV16+ biopsies exhibited increased IFN-gamma and IL-10 when compared to HPV16- (P = 0.03 and 0.04, respectively). HPV18+ biopsies exhibited decreased TNF-alpha (P = 0.009) and IFN- gamma (P = 0.01) when compared to HPV18-. In accordance to HIV status, HIV-/HPV16+ patients exhibited increased IFN-gamma when compared to those presenting HIV-/HPV16- (P = 0.007). HIV-/HPV18+ patients presented decreased IFN-gamma when compared to HIV-/HPV18- (P = 0.02). These results suggest that the presence of HPV16 infection may influence cervical lesion installation, and irrespective of HIV status, HPV18 infection may be more aggressive than HPV-16.

Adolescent↗

[Anxiety and depression symptoms assessment in pre-term neonates' mothers during and after hospitalization in neonatal intensive care unit].

OBJECTIVE: To identify clinical level of anxiety, dysphoria and depression symptoms of pre-term infants' mothers between two moments, during and after hospitalization in Neonatal Intensive Care Unit (NICU). METHODS: Previously, mothers with psychiatric background were excluded of the study. Forty-three pre-term and very low birthweight infants' mothers were assessed through State-Trait Anxiety Inventory and Beck Depression Inventory. The assessments were done during and after hospitalization, respectively. RESULTS: In the first assessment, 44% mothers showed clinical level in one or more of the emotional symptoms, such as anxiety, dysphoria or depression. After infants' discharge, the number of mothers with clinical level of emotional symptoms decreased significantly (26%) in comparison of the first assessment (p< or =0.008). The anxiety-state level decreased significantly from the first to the second assessment (from 35% to 12%; p< or =0.006). No difference in depression and dysphoria symptoms between two assessments were found. CONCLUSION: The pre-term infants' mothers presented situational anxiety and required emotional support to cope with the infants' hospitalization.

Adult↗

Ultrasound markers of fetal infection part 1: viral infections.

Diagnosis of fetal infection has depended on identification of pathogens by means of microbiological cultures, immunologic techniques, and special molecular biology techniques that can identify organisms known or suspected of being associated with adverse outcomes of pregnancy. Rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), and human immunodeficiency virus (HIV), for example, are capable of gaining access to the amniotic cavity and producing fetal infection, even when amniotic membranes are intact. Intrauterine invasion by viruses can be associated with maternal symptoms of infection or can be completely silent. In many instances extensive fetal compromise with irreversible structural damage or fetal death will have occurred by the time infection is confirmed by culture or other histopathological methods. The evidence of fetal infection may be as subtle as nascent intrauterine growth restriction (IUGR), mildly inappropriate calcification of fetal organs, placenta, cord, and membranes, and failure to adequately develop fetal fat reserves. The evidence of infection may be as dramatic as obvious fetal malformation, severe central nervous system structural damage, or fetal death. Sonography is capable of detecting most of the grave alterations and some of the subtle effects that are typical of fetal infection.

Cytomegalovirus Infections↗

Effect of maternal use of antiretroviral agents on serum insulin levels of the newborn infant.

OBJECTIVE: The aim of this study was to investigate the effect of antiretroviral drugs on neonatal serum insulin levels. RESEARCH DESIGN AND METHODS: A prospective study was conducted on 57 pregnant women divided into three groups: the zidovudine (ZDV) group, HIV-infected women taking ZDV (n = 20); the triple treatment group, HIV-infected women taking triple antiretroviral agents ZDV + lamivudine + nelfinavir (n = 25); and the control group, pregnant women considered normal from a clinical and laboratory standpoint (n = 12). Blood was collected from the umbilical cord of newborn infants upon delivery for measurement of insulin level. The insulin measurements were performed in duplicate by radioimmunoassay. RESULTS: Demographic and anthropometric data were homogeneous, and pregnant women with a personal and family history of diabetes were excluded. There was no difference between groups regarding glycemia in the newborn. Median newborn insulin doses were 2.9, 4.8, and 6.5 muU/ml for the triple treatment, ZDV, and control groups, respectively (P < 0.05). CONCLUSIONS: Use of triple therapy during pregnancy induced a significant decrease in serum levels of neonatal insulin compared with the control group. Active surveillance of short- and long-term adverse events is imperative to issue a definitive statement regarding the impact that use of protease inhibitors during pregnancy will have on infant metabolism.

Adolescent↗

Antiretroviral therapy during pregnancy and early neonatal life: consequences for HIV-exposed, uninfected children.

Women have emerged as the fastest growing human immunodeficiency virus (HIV) infected population worldwide, mainly because of the increasing occurrence of heterosexual transmission. Most infected women are of reproductive age and one of the greatest concerns for both women and their physicians is that more than 1,600 infants become infected with HIV each day. Almost all infections are a result of mother-to-child transmission of HIV. With the advent of combination antiretroviral therapies, transmission rates lower than 2% have been achieved in clinical studies. Antiretroviral compounds differ from most other new pharmaceutical agents in that they have become widely prescribed in pregnancy in the absence of proof of safety. We reviewed antiretroviral agents used in pregnant women infected with human immunodeficiency virus, mother-to-child transmission, and their consequences for infants.

Anti-HIV Agents↗

Pharmacokinetics and transplacental transfer of lidocaine and its metabolite for perineal analgesic assistance to pregnant women.

BACKGROUND: Obstetrical analgesia continues to be challenging to science in the search for safe and effective methods that will permit the use of these procedures allied to improved obstetrical and perinatal results. OBJECTIVE: The objective of the present study was to investigate the pharmacokinetics and the placental transfer of lidocaine and its metabolite in parturients whose pregnancies were resolved by the vaginal route under perineal analgesia. PATIENTS AND METHODS: The study was conducted on 23 pregnant women who received perineal analgesia with 20 ml 2% lidocaine (400 mg) during the expulsive period of labor. Maternal venous blood samples were obtained from 0 min to 360 min after drug administration, and umbilical venous blood was obtained at delivery. Lidocaine and monoethylglycinexylidide (MEGX) were determined using high-performance liquid chromatography. The fetal/maternal ratios of the drugs were determined on the basis of maternal and fetal concentrations at delivery. RESULTS: Maximum lidocaine concentrations at the median times of 15 min were 3.22 microg/ml. The pharmacokinetic parameters were: half-life t1/2alpha 24.0 min, area under the curve (AUC)0-infinity 460.2 microg/min per ml, t1/2beta 180.0 min, clearance 12.2 ml/min per kg and volume distribution 3.1 l/kg. The fetal/maternal ratio for lidocaine at delivery was 0.46, with the latency time between drug administration and delivery being 11.0 min. Maximum MEGX concentrations at the median time of 90 min were 229.0 ng/ml. The t1/2 for MEGX was 240 min, and AUC0-infinity was 82.4 microg min/ml. CONCLUSION: Lidocaine administered by the perineal route presented a tmax of 15 min, significantly lower than when the drug was administered peridurally, revealing that the time between administration and the occurrence of the analgesic effect was shorter. The study demonstrated placental transfer of lidocaine at ratios of about 50% for lidocaine at the time of delivery. The MEGX placental transfer demonstrated fetal concentration higher than the maternal at the time of delivery.

Adult↗