Some notes from cytogenetical observations in the nullisomics of Chinese spring wheat at Sasayama, Japan

Objectives: This retrospective cohort study evaluated the risk of hepatotoxicity in HIV-1 positive pregnant and non-pregnant women starting combined ART. Methods: Data were used from the ATHENA observational cohort. The study population consisted of HIV-1 infected, therapy naive, pregnant and non-pregnant women, followed between January 1997 and February 2008. Demographic, treatment and pregnancy related data were collected. Risk of hepatotoxicity was determined using univariate and multivariate logistic regression. Analyses were adjusted for age, region of origin, baseline HIV-RNA levels and CD4 cell counts, cART regimen and hepatitis B and C coinfection. ALT and AST values of more than 5 times ULN were considered as hepatotoxicity. Results: Four-hundred and twenty-five pregnant and 1121 non-pregnant women were included. Independent risk factors of hepatotoxicity in all women were the presence of detectable HCV RNA (OR 5.48, 95% CI 2.25-13.38, p <0.001) and NVP use (OR 2.63, 95% CI 1.54-4.55, p <0.001). Stratified for pregnancy, the adjusted risk of hepatotoxicity was significantly associated with HCV coinfection only during pregnancy (OR 23.53, 95% CI 4.69-118.01, p <0.001). NVP use is related to hepatotoxicity in pregnant (OR 5.26, 95% CI 1.61-16.67, p <0.005) as well as in non-pregnant women (OR 2.13, 95% CI 1.11-4.00, p = 0.02). Conclusion: HCV coinfection and NVP use are associated with a higher risk of cART induced hepatotoxicity in pregnant women. (C) 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserve

Long-Term Virological Treatment Outcomes in Adolescents and Young Adults With Perinatally and Non-Perinatally Acquired Human Immunodeficiency Virus

Background: Long-term viral suppression on antiretroviral therapy (ART) is not established among all people with human immunodeficiency virus (PWH). Young adults (18-24 years) are recognized as a group vulnerable for suboptimal virological treatment outcomes. The aim of this study is to evaluate longitudinal virological treatment outcomes and to identify risk factors for virological failure (VF) among young adults with non-perinatally and perinatally acquired human immunodeficiency virus (HIV) in the Netherlands. Methods: We included individuals registered in the national ATHENA observational cohort from 2000 until 2020 who had entered care before the age of 25 years, who had received ART for at least 6 months with at least 2 available HIV ribonucleic acid measurements between the age of 18 and 24 years. We compared VF between age groups 12-17, 18-24, and 25-30 years. A multivariable generalized linear mixed model was used to evaluate risk factors for VF. Analyses were stratified by HIV acquisition mode. Results: In total, 1174 non-perinatally PWH and 157 perinatally PWH were included. In 2020, VF rate was 7% in non-perinatally PWH young adults and 19% in perinatally PWH young adults. The adjusted risk for VF was significantly higher in those aged 18-24 compared to 25-30 years in both non-perinatally PWH (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.07-1.50) and perinatally PWH (OR, 2.34; 95% CI, 1.48-3.71). Conclusions: Young adulthood is a vulnerable period, with increased risk for VF, especially for perinatally PWH. The probability of VF decreased over time, but less for perinatally PWH compared to non-perinatally PWH

Risk of babies being born SGA <10th percentile, by univariate and multivariate analysis, using a generalized estimation equation.

<p>Risk of babies being born SGA <10th percentile, by univariate and multivariate analysis, using a generalized estimation equation.</p

Neonatal outcomes stratified for PI- and NNRTI-based regimens and based on whether cART was started before or after conception.

<p>Neonatal outcomes stratified for PI- and NNRTI-based regimens and based on whether cART was started before or after conception.</p

Baseline characteristics of HIV-negative and HIV-positive women (by group–those starting cART prior to conception and those starting cART after conception).

<p>Baseline characteristics of HIV-negative and HIV-positive women (by group–those starting cART prior to conception and those starting cART after conception).</p

Outcome of HIV-exposed uninfected (HEU) singleton infants born to HIV-positive mothers by timing of initiation of cART—preconception vs postconception.

<p>Outcome of HIV-exposed uninfected (HEU) singleton infants born to HIV-positive mothers by timing of initiation of cART—preconception vs postconception.</p

Risk of a baby being born SGA <10th percentile.

<p>Multivariate analysis using a generalized estimation equation and stratified for PI- and NNRTI-based cART regimens.</p

Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women

Objective.To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum. Methods.HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated. Results.Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, 60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing. Conclusions.Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy. Clinical Trials Registration.NCT00825929 and NCT000422890.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Etravirine pharmacokinetics in HIV-infected pregnant women

Background: The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. Methods: IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL). Results: Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred. Conclusion: Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available. Clinical Trial registration: The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929.SCOPUS: ar.jinfo:eu-repo/semantics/publishe