BACKGROUND The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear (“best-ear” hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P = 0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P = 0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P = 0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P = 0.004) and on the receptive-communication scale (P = 0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P = 0.64). CONCLUSIONS Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.)

Phagocytosis of a variety of inert and metabolically active particulates plays an essential role in metazoan nutrition, metabolic economy, and defense against viral, bacterial, and protozoan pathogens . With the development ofthe lysosome concept (1-3), the processes governing the intracellular digestion of ingested particles have been clarified. In contrast, the mechanisms which regulate the ingestion phase of phagocytosis remain poorly understood. The recognition of contractile proteins in the cytoplasm of a variety of nonmuscle cells (4-7), including macrophages (4, 5, 7), has resolved one mechanism whereby chemical energy released during phagocytosis may be coupled to mechanical processes requisite for membrane movement and particle interiorization. However, no information is available which suggests how a phagocyte directs this system of contractile elements in order to engulf specific particles which are attached to its plasma membrane . That the process is indeed specific and limited to the segments of plasma membrane to which the particles to be ingested are bound has been carefully documented (8,9).The fastidious appetite of phagocytes is also well known. These cells avidly ingest some particles with which they come into contact while they totally ignore others (8, 9) . The presence or absence of opsonins (complement and immunoglobulins) on the surface of a particle is widely recognized as the most important factor governing the fate ofthe particle . Particles coated with ligands such as IgG and/or complement are avidly ingested by phagocytes while the same particles lacking such ligands are neither bound to, nor ingested by, phagocytic cells.The experiments reported in this paper were performed to examine the mechanisms which govern the vectorial and discriminatory qualities of the phagocytic process and to define the factors responsible for the segmental nature

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We have recently described a nonnuceoside compound that specifcally inhibits the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS. This compound, nevirapine (BI-RG-587), interacts with highly conserved tyrosine residues at positions 181 and 188 in the reverse t iptase to inhibit the recombinant enzyme and virus replication in cell culture with 50% inhibitory concentrations in the 40 nM range. HIV-1 variants resistant to nevirapine emerged with passage in cell culture in the presence of drug. This resistant phenotype was stable with continued passage in the absence of drug. These mutants had a substitution of cysteine for the tyrosine at position 181.

In neonates with symptomatic congenital CMV disease, valganciclovir oral solution provides plasma concentrations of ganciclovir comparable to those achieved with administration of intravenous ganciclovir. The results of the present study cannot be extrapolated to extemporaneously compounded liquid formulations of valganciclovir.