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.
Access to reproductive health services for women with HIV is critical to ensuring their reproductive needs are addressed and their reproductive rights are protected. In addition, preventing unintended pregnancies in women with HIV is an essential component of a comprehensive prevention of mother-to-child transmission (PMTCT) programme. As a result, a call for stronger linkages between sexual and reproductive health and HIV policies, programmes and services has been issued by several international organizations. However, implementers of PMTCT and other HIV programmes have been constrained in translating these goals into practice. The obstacles include: (i) the narrow focus of current PMTCT programmes on treating HIV-positive women who are already pregnant; (ii) separate, parallel funding mechanisms for sexual and reproductive health and HIV programmes; (iii) political resistance from major HIV funders and policy-makers to include sexual and reproductive health as an important HIV programme component; and (iv) gaps in the evidence base regarding effective approaches for integrating sexual and reproductive health and HIV services.However, we now have a new opportunity to address these essential linkages. More supportive political views in the United States of America and the emergence of health systems strengthening as a priority global health initiative provide important springboards for advancing the agenda on linkages between sexual and reproductive health and HIV. By tapping into these platforms for advocating and by continuing to invest in research to identify integrated service delivery best practices, we have an opportunity to strengthen ties between the two synergistic fields.Une traduction en français de ce résumé figure à la fin de l'article. Al final del artículo se facilita una traducción al español.
IntroductionConstructively engaging male partners in women-centred health programs such as family planning and prevention of mother-to-child HIV transmission has resulted in both improved health outcomes and stronger relationships. Concerted efforts to engage men in microbicide use could make it easier for women to access and use microbicides in the future. This paper synthesizes findings from studies that investigated men's role in their partners’ microbicide use during clinical trials to inform recommendations for male engagement in women's microbicide use.MethodsWe conducted primary and secondary analyses of data from six qualitative studies implemented in conjunction with microbicide clinical trials in South Africa, Kenya, and Tanzania. The analyses included data from 535 interviews and 107 focus groups with trial participants, male partners, and community members to answer research questions on partner communication about microbicides, men's role in women's microbicide use, and potential strategies for engaging men in future microbicide introduction. We synthesized the findings across the studies and developed recommendations.ResultsThe majority of women in steady partnerships wanted agreement from their partners to use microbicides. Women used various strategies to obtain their agreement, including using the product for a while before telling their partners, giving men information gradually, and continuing to bring up microbicides until resistant partners acquiesced. Among men who were aware their partners were participating in a trial and using microbicides, involvement ranged from opposition to agreement/non-interference to active support. Both men and women expressed a desire for men to have access to information about microbicides and to be able to talk with a healthcare provider about microbicides.ConclusionsWe recommend counselling women on whether and how to involve their partners including strategies for gaining partner approval; providing couples’ counselling on microbicides so men have the opportunity to talk with providers; and targeting men with community education and mass media to increase their awareness and acceptance of microbicides. These strategies should be tested in microbicide trials, open-label studies, and demonstration projects to identify effective male engagement approaches to include in eventual microbicide introduction. Efforts to engage men must take care not to diminish women's agency to decide whether to use the product and inform their partners.
Men's limited understanding of family planning (FP) and harmful cultural gender norms pose obstacles to women's FP use. Thirty-two model men called 'Emanzis' were recruited from the community in Kabale, Uganda to lead men from their peer group through a 10-session curriculum designed to transform gender norms and motivate men to engage in FP and HIV services. Cross-sectional surveys were conducted before (n = 1251) and after (n = 1122) implementation. The Gender Equitable Men (GEM) Scale was used to assess the effect on gender attitudes. The intervention achieved negligible changes in responses to GEM items. Improvements in some gender-influenced health-seeking behaviours and practices in men were noted, specifically in visiting health facilities, HIV testing, and condom use. For future application, the intervention should be adapted to require higher peer educator qualifications, longer intervention duration, and more frequent supervision. Practical guidance is needed on where to direct investments in gender-transformative approaches for maximum impact.
Despite substantial policy support for the integration of family planning and HIV programmes, burgeoning resources for HIV ignore the potential impact of contraception on HIV prevention. Moreover, separate funding for these two programmes and the resulting vertical organisation of health ministries and service facilities undermine coordination between departments and limit providers' ability to address the contraceptive needs of HIV-positive clients. Projects integrating family planning and HIV services are being implemented, allowing for documentation of factors that facilitate or impede integrated service delivery. However, few have been evaluated to demonstrate impact on contraceptive uptake and HIV-positive births averted.
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