Alteration in cytochrome P450 3A4 activity as measured by a urine cortisol assay in HIV-1-infected pregnant women and relationship to antiretroviral pharmacokinetics.

OBJECTIVES: Pregnancy results in physiological changes altering the pharmacokinetics of drugs metabolized by cytochrome P450 3A4 (CYP3A4). The urinary ratio of 6-ß hydroxycortisol to cortisol (6ßHF : F) is a marker of CYP3A4 induction. We sought to evaluate its change in antiretroviral (ARV)-treated HIV-1-infected women and to relate this change to ARV pharmacokinetics. METHODS: Women receiving various ARVs had pharmacokinetic evaluations during the third trimester of pregnancy (>30 weeks) and postpartum with determination of 6ßHF : F carried out on the same days. The Wilcoxon signed rank test was used to compare the ratio antepartum to postpartum. The relationship between the change in ratio and the change in pharmacokinetics was analysed using Kendall's tau. RESULTS: 6ßHF : F ratios were available for 107 women antepartum, with 54 having postpartum values. The ratio was higher antepartum (P=0.033) (median comparison 1.35; 95% confidence interval 1.01, 1.81). For 71 women taking a protease inhibitor (PI), the antepartum vs. postpartum 6ßHF : F comparison was marginally significant (P=0.058). When the change in the 6ßHF : F ratio was related to the change in the dose-adjusted ARV area under the plasma concentration vs. time curve (AUC) between antepartum and postpartum, the 35 subjects in the lopinavir/ritonavir (LPV/r) arms demonstrated an inverse relationship (P=0.125), albeit this correlation did not reach statistical significance. CONCLUSIONS: A 35% increase in the urinary 6ßHF : F ratio was measured during late pregnancy compared with postpartum, indicating that CYP3A induction occurs during pregnancy. The trend towards an inverse relationship between the change in the 6ßHF : F ratio and the change in the LPV AUC antepartum vs. postpartum suggests that CYP3A induction may be one mechanism behind altered LPV exposure during pregnancy.

Effect of pregnancy on emtricitabine pharmacokinetics.

OBJECTIVES: The aim of the study was to describe emtricitabine pharmacokinetics during pregnancy and postpartum. METHODS: The International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT), formerly Pediatric AIDS Clinical Trials Group (PACTG), study P1026s is a prospective pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including a cohort taking emtricitabine 200 mg once daily. Intensive steady-state 24-hour emtricitabine pharmacokinetic profiles were performed during the third trimester and 6-12 weeks postpartum, and on maternal and umbilical cord blood samples collected at delivery. Emtricitabine was measured by liquid chromatography-mass spectrometry with a quantification limit of 0.0118 mg/L. The target emtricitabine area under the concentration versus time curve, from time 0 to 24 hours post dose (AUC(0-24) ), was ≥7 mg h/L (≤30% reduction from the typical AUC of 10 mg h/L in nonpregnant historical controls). Third-trimester and postpartum pharmacokinetics were compared within subjects. RESULTS: Twenty-six women had pharmacokinetics assessed during the third trimester (median 35 weeks of gestation) and 22 postpartum (median 8 weeks postpartum). Mean [90% confidence interval (CI)] emtricitabine pharmacokinetic parameters during the third trimester vs. postpartum were, respectively: AUC: 8.0 (7.1-8.9) vs. 9.7 (8.6-10.9) mg h/L (P = 0.072); apparent clearance (CL/F): 25.0 (22.6-28.3) vs. 20.6 (18.4-23.2) L/h (P = 0.025); 24 hour post dose concentration (C(24) ): 0.058 (0.037-0.063) vs. 0.085 (0.070-0.010) mg/L (P = 0.006). The mean cord:maternal ratio was 1.2 (90% CI 1.0-1.5). The viral load was <400 HIV-1 RNA copies/mL in 24 of 26 women in the third trimester, in 24 of 26 at delivery, and in 15 of 19 postpartum. Within-subject comparisons demonstrated significantly higher CL/F and significantly lower C(24) during pregnancy; however, the C(24) was well above the inhibitory concentration 50%, or drug concentration that suppresses viral replication by half (IC(50) ) in all subjects. CONCLUSIONS: While we found higher emtricitabine CL/F and lower C(24) and AUC during pregnancy compared with postpartum, these changes were not sufficiently large to warrant dose adjustment during pregnancy. Umbilical cord blood concentrations were similar to maternal concentrations.

Hypertension in pregnancy among HIV-infected women in sub-Saharan Africa: prevalence and infant outcomes.

This analysis was performed to determine the prevalence of hypertension and association of MAP (mean arterial pressure) with birth outcomes among HIV-infected pregnant women not taking antiretrovirals. HIV-infected pregnant women, enrolled into the HPTN024 trial in Tanzania, Malawi and Zambia were followed up at 26-30, 36 weeks, and delivery. The prevalence of hypertension was <1% at both 20-24 weeks and 26-30 weeks and 1.7% by 36 weeks. A 5 mm Hg elevation in MAP increased the risk of stillbirth at 20-24 weeks by 29% (p = 0.001), 32% (p = 0.001) at 26-30 weeks and of low birth weight (LBW) at 36 weeks by 26% (p = 0.001). MAP was not associated with stillbirth at 36 weeks, LBW prior to 36 weeks, preterm birth, neonatal mortality or the risk of maternal to child transmission (MTCT) of HIV.

Genital tract infections among HIV-infected pregnant women in Malawi, Tanzania and Zambia.

SUMMARY: The aim of this study was to compare the prevalence and factors associated with genital tract infections among HIV-infected pregnant women from African sites. Participants were recruited from Blantyre and Lilongwe, Malawi; Dar es Salaam, Tanzania; and Lusaka, Zambia. Genital tract infections were assessed at baseline. Of 2627 eligible women enrolled, 2292 were HIV-infected. Of these, 47.8% had bacterial vaginosis (BV), 22.4% had vaginal candidiasis, 18.8% had trichomoniasis, 8.5% had genital warts, 2.6% had chlamydia infection, 2.2% had genital ulcers and 1.7% had gonorrhoea. The main factors associated with genital tract infections included genital warts (adjusted odds ratio [AOR] 1.8, 95% CI 1.2-2.7), genital ulcers (AOR 2.4, 95% CI 1.2-5.1) and abnormal vaginal discharge (AOR 2.5, 95% CI 1.9-3.3) for trichomoniasis. BV was the most common genital tract infection followed by candidiasis and trichomoniasis. Differences in burdens and risk factors call for enhanced interventions for identification of genital tract infections among HIV-infected women.

Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum.

OBJECTIVES: Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum. METHODS: The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC(0-12)) was >or=10th percentile NFV AUC(0-12) in non-pregnant historical controls (18.5 microg h/mL). RESULTS: Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (C(max)), 12-h post-dose concentration (C(12)) and AUC(0-12) were significantly lower during the third trimester compared to postpartum (P

Chronic administration of nevirapine during pregnancy: impact of pregnancy on pharmacokinetics.

OBJECTIVES: To determine the impact of pregnancy on the pharmacokinetics (PK) of nevirapine (NVP) during chronic dosing in HIV-infected women and appropriate NVP dosing in this population. METHODS: Twenty-six pregnant women participating in two open-label Pediatric AIDS Clinical Trials Group studies (P1022 and P1026S) were evaluated. Each patient received 200 mg NVP every 12 h and had PK evaluations during the second or third trimester; these evaluations were repeated postpartum. Paired maternal and cord blood NVP concentrations were collected at delivery in nine patients. Ante- and postpartum comparisons were made using paired t-tests and using a 'bioequivalence' approach to determine confidence interval (CI). RESULTS: The average NVP Area Under the Curve (AUC) was 56 +/- 13 mcg(*)h/mL antepartum and 61 +/- 15 mcg(*)h/mL postpartum. The typical parameters +/- standard error were apparent clearance (CL/F)=3.51 +/- 0.18 L/h and apparent volume of distribution (Vd/F)=121 +/- 19.8 L. There were no significant differences between antepartum and postpartum AUC or pre-dose concentrations. The AUC ratio was 0.90 with a 90% CI of the mean equal to 0.80-1.02. The median (+/- standard deviation) cord blood to maternal NVP concentration ratio was 0.91 +/- 0.90. CONCLUSIONS: Pregnancy does not alter NVP PK and the standard dose (200 mg every 12 h) is appropriate during pregnancy.

Polycyclic aromatic hydrocarbon biodegradation by a subtropical white rot fungus in packed bed and suspended carrier bioreactor systems.

Application of a biotreatment system utilising immobilised white rot fungi can become an alternative for treating water or effluent contaminated by organic pollutants such as polycyclic aromatic hydrocarbons (PAHs). The application of the packed bed and suspended carrier bioreactor systems for the degradation of PAHs in synthetic polluted media using a subtropical white rot fungal isolate DSPM95 was evaluated. The white rot fungal isolate, DSPM95 could reduce a mixture of selected PAHs namely; fluorene, phenanthrene, anthracene, pyrene and benzo(a)anthracene by 50 to 96% over the reactor operation time of 31 days and when the concentration of each PAH in the feed medium was 1 mg l(-1). High manganese peroxidase and laccase activities were detectable during PAH biodegradation in both the bioreactor systems, however the maximum enzyme activities could not be sustained in the bioreactors for extended periods of time. Varying concentrations of glucose to nutrient nitrogen in the feed medium could not help sustain high enzyme production in the bioreactor. It can be concluded that the white rot fungi used here could efficiently degrade the PAH compounds in both the packed bed and suspended carrier bioreactor system, which compares well with other studies as highlighted in this report.

Acceptance of HIV-1 education & voluntary counselling/testing by & seroprevalence of HIV-1 among, pregnant women in rural south India.

BACKGROUND & OBJECTIVE: Since the first report of HIV-1 infection in Tamil Nadu, India, HIV-1 seroprevalence in India has increased steadily. Though interventions to prevent mother-to-child transmission (MTCT) are available, their implementation is a significant challenge. Therefore, among pregnant women in rural Tamil Nadu, the acceptance of education regarding HIV-1 infection and transmission and, among a systematic sample, knowledge, attitudes, and beliefs; the acceptance of HIV-1 voluntary counselling and testing (VCT); and the seroprevalence of HIV-1 infection as well as risk factors for seropositivity were assessed. METHODS: Pregnant women registered in the antenatal clinics at Namakkal District Hospital and Rasipuram Government Hospital, Tamil Nadu, India, were offered an educational session regarding HIV-1 infection and transmission. HIV-1 VCT, with informed consent, was offered. Positive results with HIV-1 rapid testing were confirmed with HIV-1 ELISA and Western blot assays. With informed consent, a systematic sample of the study population was asked to participate in pre- and posteducation assessments. Chi-square tests were used to evaluate HIV-1 risk factors. RESULTS: The educational session as well as VCT were well accepted by rural, pregnant, HIV-1- infected women. Of 3722 women registered for antenatal care at the two hospitals over a one year period, 3691 (99.2%) agreed to participate in the educational session and 3715 (99.8%) had VCT [74 had confirmed HIV-1 infection [seroprevalence: 2.0% (95% confidence interval (95%CI): 1.6%, 2.5%)]]. Of 759 eligible women, a systematic sample of 757 (99.7%) women participated in the pre- and post-education assessments. Although baseline knowledge regarding HIV-1 was limited, a highly significant improvement in such knowledge was observed (P<0.0001 for all comparisons of changes in knowledge, attitudes, and beliefs measured before and immediately after the educational session). The median per cent of correct responses increased from 26.4 per cent before the educational session to 93.8 per cent afterwards. Women whose husbands were long distance truck drivers were at increased risk of HIV-1 infection. Other factors associated with HIV-1 infection were clinical site (Namakkal District Hospital), a smaller number of persons in the household, being unmarried, and a history of previous surgeries. INTERPRETATION & CONCLUSION: The acceptability of education and of VCT among antenatal clinic attendees in this study was encouraging. However, the relatively high seroprevalence highlights the spread of HIV-1 from high risk groups to the general population and emphasizes the need for primary prevention of HIV-1 infection among adolescent girls and women of reproductive age in India.

A study of two-stage anaerobic digestion of solid potato waste using reactors under mesophilic and thermophilic conditions.

A two-stage anaerobic digestion process operated under mesophilic and thermophilic conditions was investigated for the treatment of solid potato waste to determine optimal methane yield, efficiency of operation and process stability. A solid-bed reactor was used for hydrolysis/acidification stage while an upflow anaerobic sludge blanket (UASB) reactor was used in the second stage, for methanogenesis. Three sets of conditions were investigated: (1) mesophilic + mesophilic, (II) mesophilic + thermophilic and (III) thermophilic + thermophilic in the hydrolysis/acidification and methanogenesis reactors, respectively. The methane yield was higher under mesophilic conditions (0.49 l CH4 g COD(-1)degraded) than thermophilic conditions (0.41 l CH4 g COD(-1)degraded) with reference to the methanogenic reactors. (COD)--chemical oxygen demand. However, the digestion period was shorter in systems II and III than in system I. Also, in system III the UASB reactor (thermophilic conditions) could handle a higher organic loading rate (OLR) (36 g COD 1(-1)d(-1)) than in system I (11 g COD 1(-1)d(-1)) (mesophilic conditions) with stable operation. Higher OLRs in the methanogenic reactors resulted in reactor failure due to increasing total volatile fatty acid levels. In all systems, the concentration of propionate was one of the highest, higher than acetic acid, among the volatile fatty acids in the effluent. The results show the feasibility of using a two-stage system to treat solid potato waste under both mesophilic and thermophilic conditions. If the aim is to treat solid potato waste completely within a short period of time thermophilic conditions are to be preferred, but to obtain higher methane yield mesophilic conditions are preferable and therefore there is a need to balance methane yield and complete digestion period when dealing with large quantities of solid potato waste.

Efficacy and safety of cesarean delivery for prevention of mother-to-child transmission of HIV-1.

BACKGROUND: Cesarean section before labor and before ruptured membranes ("elective cesarean section", or ECS) has been introduced as an intervention for the prevention of mother-to-child transmission (MTCT) of HIV-1. The role of mode of delivery in the management of HIV-1-infected women should be assessed in light of risks as well as benefits, since HIV-1-infected pregnant women must be provided with available information with which to make informed decisions regarding cesarean section and other options to prevent transmission of infection to their children. OBJECTIVES: Our objectives were to assess the efficacy (for prevention of MTCT of HIV-1) and the safety of ECS among HIV-1-infected women. SEARCH STRATEGY: Electronic searches were undertaken using MEDLINE and other databases. Hand searches of reference lists of pertinent reviews and studies, as well as abstracts from relevant conferences, were also conducted. Experts in the field were contacted to locate any other studies. The search strategy was iterative. SELECTION CRITERIA: Randomized clinical trials assessing the efficacy and safety of ECS for prevention of MTCT of HIV-1 were included in the analysis, as were observational studies with relevant data. DATA COLLECTION AND ANALYSIS: Data regarding HIV-1 infection status of infants born to HIV-1-infected women according to mode of delivery were extracted from the reports of the studies. Similarly, data regarding postpartum morbidity (PPM) (including minor (e.g., febrile morbidity, urinary tract infection) and major (e.g., endometritis, thromboembolism) morbidity) of the HIV-1-infected women, and infant morbidity, according to mode of delivery were extracted. MAIN RESULTS: One randomized clinical trial of the efficacy of ECS for prevention of MTCT of HIV-1 was identified. No data regarding infant morbidity according to the HIV-1-infected mother's mode of delivery were available. Data regarding PPM according to mode of delivery were available from this clinical trial as well as from five observational studies. Among HIV-1-infected women not taking antiretrovirals (ARVs) during pregnancy or taking only zidovudine, ECS was found to be efficacious for prevention of MTCT of HIV-1. PPM is generally higher among HIV-1-infected women who undergo cesarean as compared to vaginal delivery, with the risk with ECS being intermediate between that of vaginal delivery and NECS (including emergency procedures). Other factors associated with the risk of PPM among HIV-1-infected women include HIV-1 disease stage (more advanced disease, as manifested by lower CD4 counts and higher viral loads, being associated with a greater risk of PPM) and co-morbid conditions (e.g., diabetes). AUTHORS' CONCLUSIONS: ECS is an efficacious intervention for the prevention of MTCT among HIV-1-infected women not taking ARVs or taking only zidovudine. The risk of PPM with ECS is higher than that associated with vaginal delivery, yet lower than with NECS. Among HIV-1-infected women, more advanced maternal HIV-1 disease stage and concomitant medical conditions (e.g., diabetes) are independent risk factors for PPM. The risk of MTCT of HIV-1 according to mode of delivery among HIV-1-infected women with low viral loads (low either because the woman's HIV-1 disease is not advanced, or because her HIV-1 disease is well-controlled with ARVs) is unclear. Therefore, an important issue to be addressed in one or more large studies (individual studies or an individual patient data meta-analysis combining data from more than one study) is assessment of the effectiveness of ECS for prevention of MTCT of HIV-1 among HIV-1-infected women with undetectable viral loads (with or without receipt of highly active ARV therapy (HAART)).

Polycyclic aromatic hydrocarbon biodegradation in extracellular fluids and static batch cultures of selected sub-tropical white rot fungi.

Four sub-tropical white rot fungi, Trametes versicolor, Trametes pocas, Trametes cingulata and isolate DSPM95 were studied alongside the well studied white rot fungus, Phanerochaete chrysosporium, for their ability to remove polycyclic aromatic hydrocarbons (PAHs) from culture media. Both static shallow cultures and extracellular fluids were studied using media contaminated with a defined mixture of the PAHs; fluorene, phenanthrene, anthracene, pyrene and benzo(a)anthracene. With all isolates, the total loss of the parent compound in 31 days was high for fluorene, at +60%, phenanthrene at +40% and anthracene at +42%. Biotransformation of pyrene and benzo(a)anthracene by all the isolates was low, with the highest reduction of pyrene of 15.2% and benzo(a)anthracene of 15.8% being achieved with P. chrysosporium. Disappearance of the more condensed PAHs, pyrene and benzo(a)anthracene, increased in shallow static cultures with the addition of glucose and glucose oxidase as a source of additional H2O2. The addition of Mn2+ and ABTS (2,2-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)) to culture supernatants was associated with higher levels of biotransformation. Comparison of the isolates T. versicolor, T. pocas, T. cingulata and isolate DSPM95 with P. chrysosporium showed that these strains were competitive in the reduction of the PAHs, reducing the PAHs by more or less the same magnitude. Also these sub-tropical isolates did not accumulate a lot of HPLC detectable metabolites as much as P. chrysosporium.

Considerations on the measurement of practical peak voltage in diagnostic radiology.

An evaluation of the non-invasive measurement of the practical peak voltage (PPV) in the quality control of X-ray units used in diagnostic radiology was carried out. Two instruments were employed: the PTW Diavolt Universal Tester with readings in PPV and the Waveform Tester for X-rays (WATEX) prototype proposed here, which uses a PIN structure (P-type diffusion, Intrinsic region, N-type diffusion) photodiode as a sensor. The reference for the measurements was the voltage signal obtained in an oscilloscope from an invasive high voltage divider in order to verify the accuracy and precision of the measurements. The readings of the PPV in the Diavolt show a systematic error between 1% and 8%, always being less than the real value. An explanation for this difference is proposed, based on the relation between the effect of the X-rays in the film and the response of the sensor to the product of the applied voltage to the X-ray tube (peak voltage kVp), and the anode current. This explanation was confirmed using the WATEX waveform tester.

Alternatives to HIV-1 RNA concentration and CD4 count to predict mortality in HIV-1-infected children in resource-poor settings.

Cheaper, simpler alternatives to CD4 lymphocyte count and HIV-1 RNA detection for assessing the prognosis of HIV-1 infection are needed for resource-poor settings. However, little is known about the predictive value of alternative assays, in particular in children. We assessed the prognostic value of total lymphocyte count, immune complex-dissociated p24 antigen, white blood cell count, packed-cell volume (haematocrit), and serum albumin for mortality in 376 HIV-1-infected, mainly African-American or Hispanic children enrolled during March, 1988 to January, 1991. In a Cox proportional hazards model, including all assay-alternatives to CD4 and RNA, total lymphocyte count (p<0.0001) and serum albumin (p=0.0107) independently predicted mortality. Further assessment of these markers is warranted in resource-poor settings.

Production of laccase by a newly isolated strain of Trametes modesta.

The effects of the carbon and nitrogen sources, initial pH and incubation temperature on laccase production by Trametes modesta were evaluated using the one-factor-at-a-time method. The final optimisation was done using a central composite design resulting in a four-fold increase of the laccase activity to 178 nkat ml(-1). Response-surface analysis showed that 7.34 g l(-1) wheat bran, 0.87 g l(-1) glucose, 2.9 g l(-1) yeast extract, 0.25 g l(-1) ammonium chloride, an initial pH of 6.95 and an incubation temperature of 30.26 degrees C were the optimal conditions for laccase production. Laccase produced by T. modesta was fully active at pH 4 and at 50 degrees C. The laccase was very stable at pH 4.5 and at 40 degrees C but half-lives decreased to 120 and 125 min at higher temperature (60 degrees C) and lower pH (pH 3).

Biodegradation of the organochlorine pesticide, lindane by a sub-tropical white rot fungus in batch and packed bed bioreactor systems.

The degradation of the organochlorine pesticide, lindane by a sub-tropical white rot fungus DSPM95 was studied in stationary batch and packed bed bioreactor systems. Pesticide concentrations of 5, 10, 20 and 40 ppm were used in batch cultures while concentrations of 1, 2, 5 and 10 ppm were used in the packed bed bioreactor. Biodegradation of 82 +/- 6% was achieved in batch cultures at concentrations of 5 and 10 ppm. The highest percent degradation achieved in the packed bed reactor was 81% at lindane concentrations of 1 and 2 ppm and the degradation decreased at 10 ppm. The amount of lindane degraded was directly proportional to the initial lindane concentration in the medium. Laccase and manganese peroxidase were produced in both stationary batch and in immobilised cultures, however high enzyme levels could not be sustained for long periods in the packed bed bioreactor.

Ligninolytic enzyme production in selected sub-tropical white rot fungi under different culture conditions.

Lignin peroxidase (LiP), manganese peroxidase (MnP) and laccase activities in selected sub-tropical white rot fungal species from Zimbabwe were determined. The enzyme activities were assayed at varying concentrations of C, N and Mn2+. Manganese peroxidase and laccase activities were the only expressed activities in the fungi under the culture conditions tested. Trametes species, T. cingulata, T. elegans and T. pocas produced the highest manganese peroxidase activities in a medium containing high carbon and low nitrogen conditions. High nitrogen conditions favoured high manganese peroxidase activity in DSPM95, L. velutinus and Irpex spp. High manganese peroxidase activity was notable for T. versicolor when both carbon and nitrogen in the medium were present at high levels. Laccase production by the isolates was highest under conditions of high nitrogen and those conditions with both nitrogen and carbon at high concentration. Mn2+ concentrations between 11-25 ppm gave the highest manganese peroxidase activity compared to a concentration of 40 ppm or when there was no Mn2+ added. Laccase activity was less influenced by Mn2+ levels. While some laccase activity was produced in the absence of Mn2+, the enzyme levels were higher when Mn2+ was added to the culture medium.

Growth, dye degradation and ligninolytic activity studies on Zimbabwean white rot fungi.

White rot fungi were collected from Chirinda and Chimanimani hardwood forests in Zimbabwe and studied with respect to growth temperature optima and dye decolorization. Temperature optima were found to vary (between 25-37 degrees C) amongst the isolates. The isolates were screened for their ability to degrade the polymeric dyes; blue dextran and Poly R478 and the triphenylmethane dyes; cresol red, crystal violet and bromophenol blue. Semi-quantitative determination of the hydrolytic enzyme activities possessed by the white rot fungi was determined using the API ZYM system. Lignin peroxidase (LiP), manganese peroxidase (MnP) and laccase activities in the fungi were also determined. No LiP was detected in any of the isolates but all isolates showed manganese peroxidase and laccase activities. Time related decolorization studies and optimum pH determinations for Poly R478 degradation by the isolates were carried out in liquid cultures. The most significant rates of Poly R478 decolorization in liquid cultures were found with the following isolates: Trametes cingulata, Trametes versicolor, Trametes pocas, DSPM95 (a species to be identified), Datronia concentrica and Pycnoporus sanguineus.

Mode of delivery and postpartum morbidity among HIV-infected women: the women and infants transmission study.

Cesarean delivery before onset of labor and rupture of membranes (i.e., scheduled cesarean delivery) is associated with a lower risk of vertical transmission of HIV. The following a priori hypotheses were tested: among HIV-infected women, scheduled cesarean delivery is associated with a higher risk of postpartum morbidity, longer hospitalization, and a higher risk of rehospitalization than spontaneous vaginal delivery. Postpartum morbidity occurred following 178 of 1,186 (15%) of deliveries during 1990 to 1998 in The Women and Infants Transmission Study. The most commonly reported postpartum morbidity events were: fever without infection, hemorrhage or severe anemia, endometritis, urinary tract infection, and cesarean wound complications. Several time trends were observed: the median duration of ruptured membranes decreased (p < .001), intrapartum antibiotic use increased (p < .001), the median antepartum plasma HIV RNA concentration decreased (p < .001), and the incidence of any postpartum morbidity decreased (p = .02). With spontaneous vaginal delivery as the reference category, both scheduled (odds ratio [OR] = 4.69; 95% confidence interval [95% CI], 2.03-10.84), and nonscheduled (OR, 2.50; 95% CI, 1.24-5.04) cesarean deliveries were associated with fever without infection; with urinary tract infection (OR, 3.79; 95% CI 1.04-13.85; OR, 3.86; 95% CI, 1.55-9.60, respectively), and with any postpartum morbidity (OR, 3.19; 95% CI 1.69-6.00; OR, 4.10; 95% CI, 2.71-6.19, respectively). Nonscheduled cesarean deliveries were more likely to be complicated by endometritis (OR, 6.98; 95% CI, 3.53-13.78). Adjusted ORs relating mode of delivery and each of the outcomes (fever without infection, urinary tract infection, endometritis, and any postpartum morbidity) were similar to unadjusted ORs. Results of this analysis indicate scheduled cesarean delivery is associated with an increased risk of any postpartum morbidity and, specifically, postpartum fever without infection. The potential for postpartum morbidity with scheduled cesarean delivery should be considered in light of possible adverse events associated with other interventions to decrease the risk of vertical transmission of HIV. Counseling of HIV-infected pregnant women regarding scheduled cesarean delivery as a possible intervention to decrease maternal-infant transmission of HIV should include discussion of these results, as well as new data as they become available, regarding the incidence and severity of postpartum morbidity events among HIV-infected women according to mode of delivery.

Cesarean section delivery to prevent vertical transmission of human immunodeficiency virus type 1. Associated risks and other considerations.

Delivery by elective cesarean section (ECS), cesarean section prior to labor and rupture of membranes, is associated with a lower rate of vertical transmission of HIV compared with other modes of delivery. The efficacy of ECS among women receiving combination antiretroviral therapy or among women with low viral loads is unknown. In assessing the possible utility of ECS as an intervention to decrease vertical transmission in the United States and other countries, the potential risks associated with operative delivery as well as other considerations should also be addressed. Although cesarean section delivery is associated with an increased rate of postpartum morbidity compared with vaginal delivery in the general population, operative delivery performed emergently carries a higher risk of complications than scheduled or elective procedures. Analyses of the risk of postpartum morbidity according to mode of delivery among HIV-infected women have been performed in the Women and Infants Transmission Study (WITS), the largest database in North America with relevant data, as well as other, smaller databases. These analyses suggest a similar pattern to that observed in the general population. In addition to quantifying the incidence of postpartum morbidity events, it is also important to distinguish between minor and major morbidity. Neonatal morbidity related to ECS is generally due to iatrogenic preterm birth, that is, situations where the gestational age is not accurately assessed prior to delivery. Occupationally acquired HIV infection related to obstetric procedures is a possibility, although risk related to mode of delivery is unknown. The results of economic analyses of ECS compared to vaginal delivery in the US indicate that ECS is a cost-effective intervention in preventing vertical transmission of HIV among women who refrain from breastfeeding. However, more precise estimates of the risk of vertical transmission among women receiving combination antiretroviral therapy and of the potential risks of maternal and pediatric adverse events related to receipt of such therapy are needed. In summary, the benefit of ECS must be weighed against potential risks, and issues such as cost-effectiveness also should be taken into consideration.

Oral ganciclovir in children: pharmacokinetics, safety, tolerance, and antiviral effects. The Pediatric AIDS Clinical Trials Group.

The pharmacokinetics, safety, tolerance, and antiviral effects of ganciclovir (Gcv) administered orally were evaluated in 36 children infected with cytomegalovirus (CMV) who were severely immunocompromised by infection with human immunodeficiency virus type 1. In this dose-escalation study, 30 mg/kg of Gcv administered every 8 h produced serum levels similar to the dose (1 g/8 h) effective for maintenance treatment of CMV retinitis in adults. In older children, serum Gcv concentrations were similar after the administration of capsules and suspension. All doses (10-50 mg/kg/8 h) studied were safe and, except for the volume of suspension or number of pills, were well tolerated. Oral Gcv was associated with a decrease in the detection of CMV by culture or polymerase chain reaction. CMV disease occurred in 3 children during the study: one developed Gcv resistance, another had harbored resistant virus at study entry, and a third had wild-type CMV