Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women.

OBJECTIVES: HIV antiretroviral therapy during pregnancy is recommended to reduce the risk of mother-to-child transmission and for maternal care. Physiological changes during pregnancy can affect pharmacokinetics. The impact of pregnancy was evaluated for once-daily (qd) darunavir/ritonavir. METHODS: HIV-1-infected pregnant women on an antiretroviral regimen that includes darunavir were enrolled in the study and further treated with darunavir/ritonavir 800/100 mg qd. Plasma concentrations were assessed over 24 h during the second and third trimesters and postpartum using a validated high-performance liquid chromatography tandem mass spectrometry assay for total darunavir and ritonavir, and using (14) C-darunavir-fortified plasma for unbound darunavir. Pharmacokinetic parameters were derived using noncompartmental analysis. Safety and antiviral response were assessed at all visits. RESULTS: Data were available for 16 women. The area under the plasma concentration-time curve from 0 to 24 h (AUC24h ) for total darunavir was 34-35% lower during pregnancy vs. postpartum. Unbound darunavir AUC24h was 20-24% lower during pregnancy vs. postpartum. The minimum plasma concentration of total and unbound darunavir was 32-50% and 13-38% lower, respectively, during pregnancy vs. postpartum. The antiviral response (< 50 HIV-1 RNA copies/mL) was 59% at baseline and increased to 87-100% during the trial; the CD4 count increased over time. One serious adverse event (gestational diabetes) was judged as possibly related to study medication. All 16 infants born to women remaining in the study at delivery were HIV-1 negative (two were premature). CONCLUSIONS: Total darunavir exposure decreased during pregnancy, but the decrease was less for unbound (active) darunavir. These changes are not considered clinically relevant. Darunavir/ritonavir 800/100 mg qd may therefore be a treatment option for HIV-1-infected pregnant women.

Economic Threshold for Cotton Aphid (Hemiptera: Aphididae) on Cotton in the Southwestern United States.

Cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a common pest of cotton throughout much of the world. In the United States, insecticide applications targeting cotton aphid in cotton are common in the Mid-South, Texas, and California. Cotton aphid population dynamics data were collected from eight insecticide efficacy trials conducted in Lubbock, TX, over a 4-yr period. Among the field populations in the nontreated plots, the instantaneous rate of population growth averaged 0.56 ± 0.608, and the mean population doubling time was 3.97 ± 2.16 d. For calculating economic injury levels (EIL) and thresholds, control costs were set at US$30.50/ha, market prices were evaluated at US$0.88, US$1.33, US$1.77, and US$2.21 kg-lint, and cotton yield potentials were evaluated at 672, 896, and 1,120 kg-lint/ha. The EIL we calculated ranged from 66 to 272 aphids per leaf, and averaged 137 aphids per leaf. Economic thresholds (ET) were calculated based on lead times of 1, 3, 5, and 7 d before EIL occurs. The mean ET across control cost, market price, and yield potential were 110 ± 48, 70 ± 31, 45 ± 19, and 29 ± 13 aphids per leaf at lead times of 1, 3, 5, and 7 d, respectively. Most curative pest management tactics in cotton are implemented within 3 d of determining need, and the ET at 3 d that we calculated (70 ± 31 aphids per leaf) overlaps the current recommended action threshold in Texas and California of 50 aphids per leaf.

Total and unbound darunavir pharmacokinetics in pregnant women infected with HIV-1: results of a study of darunavir/ritonavir 600/100 mg administered twice daily.

OBJECTIVES: Antiretroviral therapy during pregnancy is recommended to reduce the risk of mother-to-child transmission of HIV and for maternal care management. Physiological changes during pregnancy can affect pharmacokinetics, potentially altering pharmacological activity. We therefore evaluated the pharmacokinetics of twice-daily (bid) darunavir in HIV-1-infected pregnant women. METHODS: HIV-1-infected pregnant women receiving an antiretroviral regimen containing darunavir/ritonavir 600/100 mg bid were enrolled in this study. Total and unbound darunavir and total ritonavir plasma concentrations were obtained over 12 h during the second and third trimesters and postpartum. Total darunavir and ritonavir plasma concentrations were determined using a validated high-performance liquid chromatography tandem mass spectrometry assay and unbound darunavir was determined using (14) C-darunavir-fortified plasma. Pharmacokinetic parameters were derived using noncompartmental analysis. RESULTS: Data were available for 14 women. The area under the plasma concentration-time curve from 0 to 12 h (AUC12h) for total darunavir was 17-24% lower during pregnancy than postpartum. The AUC12h for unbound darunavir was minimally reduced during pregnancy vs. postpartum. The minimum plasma concentration (Cmin) of total and unbound darunavir was on average 43-86% and 10-14% higher, respectively, during pregnancy vs. postpartum. The antiviral response (< 50 HIV-1 RNA copies/mL) was 33% at baseline and increased to 73-90% during treatment; the percentage CD4 count increased over time. One serious adverse event was reported (increased transaminase). All 12 infants born to women remaining in the study at delivery were HIV-1-negative; four of these infants were premature. CONCLUSIONS: Total darunavir exposure decreased during pregnancy. No clinically relevant change in unbound (active) darunavir occurred during pregnancy, suggesting that no dose adjustment is required for darunavir/ritonavir 600/100 mg bid in pregnant women.

Variability in Time and Space of Meloidogyne incognita Fall Population Density in Cotton Fields.

Three cotton fields infested with Meloidogyne incognita were intensively sampled in the fall for 3 years (1996 to 1998) to determine if intensive sampling for M. incognita, for which spatial location is important, was necessary every year in a continuous cotton system. Two composite soil samples (20 cores each), taken over an area covering one-third of the field length and two rows wide, were averaged to represent that area (row-location combination). Each field (except one) had 24 areas assayed for changes in M. incognita population density (Pf) over a 3-year period. At all three sites, Pf was higher during fall 1998 than fall 1996. There were no differences in Pf between rows within a year or between years (no. row x year interaction) at any of the sites. At all three sites, there was a consistent difference each year in Pf among locations in a field (no. year x location interaction). At each area, M. incognital/500 cm(3) was labeled for one of four Pf classes: <250, 250 to 999, 1,000 to 2,499, and >/= 2,500. Management of root-knot nematode would likely be altered as classification changed. The areas that were reclassified by two classes or more after 1 and 2 years ranged from 0 to 29% and 25 to 54%, respectively. The risk of underestimating Pf of M. incognita was higher in one site 2 years after the initial intensive sampling procedure, whereas in another site there was little change in Pf 2 years after initial sampling. Sampling frequency will need to be decided on a field-by-field basis.

Comparison of Variable and Single-Rate Applications of Aldicarb on Cotton Yield in Fields Infested with Meloidogyne incognita.

Variable-rate applications of the nematicide aldicarb were compared to producer standard rates in eight field tests over 3 years. Test areas (308 to 1,015 m long) were divided into eight or five blocks. Each block contained two plots with a variable-rate treatment (VRT) of aldicarb and a producer standard treatment (PST) of aldicarb. Each VRT plot was divided into three subunits and intensively sampled for Meloidogyne incognita in either the fall or spring before planting. Rates of aldicarb were assigned to each subunit for VRT based on M. incognita population density. In three of the eight tests, VRT resulted in either higher yield or similar yields, but less nematicide applied. In two tests there were no differences between PST and VRT in yields or average rates of aldicarb applied. In three tests, VRT used more aldicarb (>0.17 kg a.i./ha difference) than PST and yields were not significantly different between treatments. In two of the cases where VRT was superior to PST, the producer's rate of aldicarb was judged to be either too low or too high for the average M. incognita density present in the field. In all three cases where PST was superior to VRT, perennial weeds were an important factor also limiting yield. Variable-rate application of aldicarb did not consistently provide for higher yields or lower nematicide usage than standard application rates.

Need for cognition related to time perception.

Undergraduates who scored high on need for cognition tended to underestimate a 90-sec. filled interval and their number of correct single solution anagrams tended to correlate negatively with estimated time. Subjects high in need for cognition reported the task was easy but enjoyment and prior experience were similar.