Infant Safety during and after Maternal Valacyclovir Therapy in Conjunction with Antiretroviral HIV-1 Prophylaxis in a Randomized Clinical Trial

<div><h3>Background</h3><p>Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.</p> <h3>Methods</h3><p>Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm³ were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher’s Exact and Wilcoxon rank-sum tests were used for analysis.</p> <h3>Results</h3><p>One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6–4.19).</p> <h3>Conclusions</h3><p>Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.</p> <h3>Trial Registration</h3><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00530777">NCT00530777</a></p> </div

In vitro colonization of date palm plants by Rhizophagus irregularis during the rooting stage

The use of in vitro culture of date palm plants Phoenix dactylifera, associated with arbuscular mycorrhizal (AM) fungi is a novel approach for the production of bio-fortified plants that are free of pathogens. Here, we report, for the first time, the in vitro mycorrhization of in vitro date palm plants using the AM fungus Rhizophagus irregularis MUCL 41833. Date Plants were used in an in vitro cultured system that consisted of a root compartment (RC) containing germinated seeds of Barrel Clover, Medicago truncatula, and spores of Rhizophagus irregularis as a mycorrhizal donor, and a hyphal compartment (HC) with a barrier separating the RC from the HC. In vitro cultured date palm plants, at the two-leaf stage, were placed in the HC section of the culture plate that after 6 weeks contained an active growing extraradical mycelium network of the fungus. Roots of the date palm became colonized after 10 weeks and hyphae, vesicles, spores and arbuscules, were detected. No differences were noticed in above-ground parameters between mycorrhized and non-mycorrhized plants, in which there was no fungus in the HC. However, the total root length was significantly higher and secondary and tertiary roots were significantly more numerous, in the mycorrhized plants. It is hypothesized that these differences are related to stimulating molecules released by the profuse extraradical mycelium of the fungus growing in close contact with the palm root system. Root colonization percentages were of the same order as those reported in pots cultures of the date palm plants. This work opens the door for the large-scale in vitro mycorrhization of date palm plants, potentially better adapted to acclimatization phase and possibly to the field