Safety and pharmacokinetics of nelfinavir during the second and third trimesters of pregnancy and postpartum.

PURPOSE: Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infected women. METHODS: Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations. RESULTS: Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants. CONCLUSIONS: Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy.

Characteristics of women who deliver with no prenatal care.

OBJECTIVE: To compare the characteristics, morbidities and pregnancy outcomes of women with no prenatal care and women receiving some care. METHODS: Medical records were abstracted for demographic variables as well as information concerning substance abuse, sexually transmitted diseases and perinatal outcome. Bivariate associations of descriptive data were tested using odds ratios or Fisher's exact test. Multivariate analysis determined adjusted odds ratios. Significance was set at alpha=0.05. RESULTS: Women who received no prenatal care were more likely to be multiparous, living with at least one child, less educated, uninsured, smoke, use cocaine and have a prior history of substance abuse. Preterm labor, preterm delivery, low birth weight and stillbirth were more common. Syphilis and HIV were found in nearly 5% of women without care. CONCLUSION: Intensive interventions are needed for women who fail to receive prenatal care so as to link these high-risk women to needed services.

Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine. Pediatric AIDS Clinical Trials Group 185 Team.

OBJECTIVE: To evaluate independent contributions of maternal factors to adverse pregnancy outcomes (APO) in HIV-infected women receiving antiretroviral therapy (ART). DESIGN: Risk factors for preterm birth (< 37 weeks gestation), low birth weight (LBW) (< 2500 g), and intrauterine growth retardation (IUGR) (birth weight < 10th percentile for gestational age) examined in 497 HIV-infected pregnant women enrolled in PACTG 185, a perinatal clinical trial. METHODS: HIV RNA copy number, culture titer, and CD4 lymphocyte counts were measured during pregnancy. Information collected included antenatal use of cigarettes, alcohol, illicit drugs; ART; obstetric history and complications. RESULTS: Eighty-six percent were minority race/ethnicity; 86% received antenatal monotherapy, predominantly zidovudine (ZDV), and 14% received combination antiretrovirals. Preterm birth occurred in 17%, LBW in 13%, IUGR in 6%. Risk of preterm birth was independently associated with prior preterm birth [odds ratio (OR) 3.34; P < 0.001], multiple gestation (OR, 6.02; P = 0.011), antenatal alcohol use (OR, 1.91; P = 0.038), and antenatal diagnosis of genital herpes (OR, 0.24; P = 0.022) or pre-eclampsia (OR, 6.36; P = 0.025). LBW was associated with antenatal diagnosis of genital herpes (OR, 0.08; P = 0.014) and pre-eclampsia (OR, 5.25; P = 0.049), and baseline HIV culture titer (OR, 1.41; P = 0.037). IUGR was associated with multiple gestation (OR, 8.20; P = 0.010), antenatal cigarette use (OR, 3.60; P = 0.008), and pre-eclampsia (OR, 12.90; P = 0.007). Maternal immune status and HIV RNA copy number were not associated with APO. CONCLUSIONS: Risk factors for APO in antiretroviral treated HIV-infected women are similar to those reported for uninfected women. These data suggest that provision of prenatal care and ART may reduce APO.

Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes.

The identification of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in 1989 represents a landmark accomplishment in human genetics. Since that time, there have been numerous advances in elucidating the function of the encoded protein and the physiological basis of cystic fibrosis. However, numerous areas of cystic fibrosis biology require additional investigation, some of which would be facilitated by information about the long-range sequence context of the CFTR gene. For example, the latter might provide clues about the sequence elements responsible for the temporal and spatial regulation of CFTR expression. We thus sought to establish the sequence of the chromosomal segments encompassing the human CFTR and mouse Cftr genes, with the hope of identifying conserved regions of biologic interest by sequence comparison. Bacterial clone-based physical maps of the relevant human and mouse genomic regions were constructed, and minimally overlapping sets of clones were selected and sequenced, eventually yielding approximately 1.6 Mb and approximately 358 kb of contiguous human and mouse sequence, respectively. These efforts have produced the complete sequence of the approximately 189-kb and approximately 152-kb segments containing the human CFTR and mouse Cftr genes, respectively, as well as significant amounts of flanking DNA. Analyses of the resulting data provide insights about the organization of the CFTR/Cftr genes and potential sequence elements regulating their expression. Furthermore, the generated sequence reveals the precise architecture of genes residing near CFTR/Cftr, including one known gene (WNT2/Wnt2) and two previously unknown genes that immediately flank CFTR/Cftr.

Two new coccidian parasites from the grand anglehead lizard, Gonocephalus grandis from Peninsular Malaysia.

During 3 collecting expeditions between October 1996 and December 1996, fecal samples were obtained from 43 adult Gonocephalus grandis from Tanah Rata and the Cameron Highlands in Peninsular Malaysia. Two species of coccidia (Isospora gonocephali n. sp. [9/43, 23%] and Eimeria cameronensis n. sp. [3/43, 7%]) were discovered. Sporulated oocysts of I. gonocephali are subspherical to ovoidal, 22.3 x 18.7 (19-25 x 17-23) microm with a bilayered wall composed of a thin inner wall and a striated outer wall with a pitted surface; oocyst residuum absent; 1 polar granule present; sporocysts are almond-shaped, 13.5 x 9.2 (12-15 x 8.5-10) microm, Stieda body broad, domelike, substieda body fanlike, sporocyst residuum consisting of coarse, nonuniform granules in an amorphous cluster; sporozoites sausage-shaped with 1 large terminal, refractile body and lay randomly in the sporocyst. Sporulated oocysts of E. cameronensis are bilayered, smooth-walled, ellipsoidal, 26.5 x 12.4 (25-28 x 12-13) microm; with 1, small, polar granule composed of 2-3 splinter-like structures fused together; oocyst residuum absent; sporocysts ovoidal, almost rectangular-shaped 8.8 x 6.6 (8-9 x 5-7) microm, with no Stieda or substieda bodies, containing scattered residuum and 2 sausage-shaped sporozoites with 1 terminal, ovoidal refractile body. No individual lizard was host to both coccidian species.