Contraception to prevent HIV-positive births: current contribution and potential cost savings in PEPFAR countries.

OBJECTIVES: To estimate the number of HIV-positive births currently prevented by contraceptive use in the President's Emergency Plan for AIDS Relief (PEPFAR) focus countries and to estimate the first year cost savings to each country if unintended and unwanted HIV-positive births were prevented via contraceptive use rather than providing antiretroviral prophylaxis for HIV-positive pregnant women ("PMTCT services"). METHODS: Data from publicly available sources yielded estimates of (1) contraceptive and HIV prevalence; (2) the number of women of reproductive age; (3) the number of annual births to HIV-infected women; (4) the rates of pregnancy and vertical HIV transmission; (5) the proportions of unintended and unwanted births; and (6) the cost per HIV-positive birth averted by family planning and PMTCT services. The number of HIV-positive births currently averted by contraceptive use and the number of unwanted and unintended HIV-positive births are the product of these estimates. Cost savings are the difference in the costs of family planning and PMTCT services. RESULTS: The annual number of unintended HIV-positive births currently averted by contraceptive use ranges from 178 in Guyana to over 120 000 in South Africa. The minimum annual cost savings to prevent just the unwanted HIV-positive births ranges from $26 000 in Vietnam to over $2.2 million in South Africa. CONCLUSIONS: 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.

From effectiveness to impact: contraception as an HIV prevention intervention.

BACKGROUND: Most efforts to date to prevent mother-to-child transmission of HIV have focused on provision of antiretroviral prophylaxis to HIV-infected pregnant women. Increasing voluntary contraceptive use has been an underused approach, despite clear evidence that preventing pregnancies in HIV-infected women who do not wish to become pregnant is an effective strategy for reducing HIV-positive births. This paper reviews international, country and service delivery level opportunities for and obstacles to translating contraceptive efficacy into interventions that will have an impact on the effectiveness of HIV prevention. METHODS: The integration of family planning services and HIV programmes as a potential intervention were specifically reviewed. RESULTS AND CONCLUSIONS: 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.

Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors.

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.