We have investigated the infectious entry pathway of adeno-associated virus (AAV) and recombinant AAV vectors by assessing AAV-mediated gene transfer and by covalently conjugating fluorophores to AAV and monitoring entry by fluorescence microscopy. We examined AAV entry in HeLa cells and in HeLa cell lines which inducibly expressed a dominant interfering mutant of dynamin. The data demonstrate that AAV internalizes rapidly by standard receptor-mediated endocytosis from clathrin-coated pits (half-time <10 min). The lysosomotropic agents ammonium chloride and bafilomycin A 1 prevent AAV-mediated gene transfer when present during the first 30 min after the onset of endocytosis, indicating that AAV escapes from early endosomes yet requires an acidic environment for penetration into the cytosol. Following release from the endosome, AAV rapidly moves to the cell nucleus and accumulates perinuclearly beginning within 30 min after the onset of endocytosis. We present data indicating that escape of AAV from the endosome and trafficking of viral particles to the nucleus are unaffected by the presence of adenovirus, the primary helper virus for a productive AAV infection. Within 2 h, viral particles could be detected within the cell nucleus, suggesting that AAV enters the nucleus prior to uncoating. Interestingly, the majority of the intracellular virus particles remain in a stable perinuclear compartment even though gene expression from nuclear AAV genomes can be detected. This suggests that the process of nuclear entry is rate limiting or that AAV entry involves multiple pathways. Nevertheless, these data establish specific points in the AAV infectious entry process and have allowed the generation of a model for future expansion to specific cell types and AAV vector analysis in vivo.

Contraception is already having an important effect on reducing the number of infant HIV infections. This contribution could be strengthened by additional efforts to provide contraception to HIV-infected women who do not wish to become pregnant. Moreover, the effect of contraception can be achieved at a cost savings compared with PMTCT services.

Acts scales, the most common way of measuring partner violence, have been criticized for being too simplistic to capture the complexities of partner violence. An alternative measurement approach is to use typologies that consider various aspects of context. In this study, the authors identified typologies of dating violence perpetration by adolescents. They conducted in-depth interviews with 116 girls and boys previously identified by an acts scale as perpetrators of dating violence. They provided narrative descriptions of their dating violence acts. For boys and girls, many acts considered violent by the acts scale were subsequently recanted or described as nonviolent. From the narratives, they identified four types of female perpetration that were distinguished by motives, precipitating events, and the abuse history of the partners. One type of perpetration accounted for most acts by boys. The findings are discussed relative to dating violence measurement, prevention and treatment, and development of theory.

Our review reveals an expanding evidence base for integrated family planning/HIV service delivery innovations. However, the modest observed effect under typical settings and the evidence of weak intervention implementation emphasize the need for stronger programmatic efforts and implementation research to address the health system obstacles to integrating these two essential services.