Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities

There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing discussion, in June 2009, the Bill & Melinda Gates Foundation sponsored a Planning for PrEP conference with stakeholders to review expected trial results, outline responsible educational approaches, and develop potential delivery and implementation strategies. The conference reinforced the need for continued and sustained dialogue to identify where PrEP implementation may fit best within an integrated HIV prevention package. This paper identifies the key action points that emerged from the Planning for PrEP meeting

Decreased Survival of B Cells of HIV-viremic Patients Mediated by Altered Expression of Receptors of the TNF Superfamily

Human immunodeficiency virus (HIV) infection leads to numerous perturbations of B cells through mechanisms that remain elusive. We performed DNA microarray, phenotypic, and functional analyses in an effort to elucidate mechanisms of B cell perturbation associated with ongoing HIV replication. 42 genes were up-regulated in B cells of HIV-viremic patients when compared with HIV-aviremic and HIV-negative patients, the majority of which were interferon (IFN)-stimulated or associated with terminal differentiation. Flow cytometry confirmed these increases and indicated that CD21low B cells, enhanced in HIV-viremic patients, were largely responsible for the changes. Increased expression of the tumor necrosis factor (TNF) superfamily (TNFSF) receptor CD95 correlated with increased susceptibility to CD95-mediated apoptosis of CD21low B cells, which, in turn, correlated with HIV plasma viremia. Increased expression of BCMA, a weak TNFSF receptor for B lymphocyte stimulator (BLyS), on CD21low B cells was associated with a concomitant reduction in the expression of the more potent BLyS receptor, BAFF-R, that resulted in reduced BLyS binding and BLyS-mediated survival. These findings demonstrate that altered expression of genes associated with IFN stimulation and terminal differentiation in B cells of HIV-viremic patients lead to an increased propensity to cell death, which may have substantial deleterious effects on B cell responsiveness to antigenic stimulation

Engaging Men in Prevention and Care for HIV/AIDS in Africa

Ed Mills and colleagues argue that a more balanced approach to gender is needed so that both men and women are involved in HIV treatment and prevention

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic

Attitudes and Acceptance of Oral and Parenteral HIV Preexposure Prophylaxis among Potential User Groups: A Multinational Study

BACKGROUND: The use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to determine uptake. METHODS AND FINDINGS: Surveys of willingness to use PrEP products were conducted with 1,790 members of potential user groups (FSWs, MSM, IDUs, SDCs and young women) in seven countries: Peru, Ukraine, India, Kenya, Botswana, Uganda and South Africa. Analyses of variance were used to assess levels of acceptance across different user groups and countries. Conjoint analysis was used to examine the attitudes and preferences towards hypothetical and known attributes of PrEP programs and medications. Overall, members of potential user groups were willing to consider taking PrEP (61% reported that they would definitely use PrEP). Current results demonstrate that key user groups in different countries perceived PrEP as giving them new possibilities in their lives and would consider using it as soon as it becomes available. These results were maintained when subjects were reminded of potential side effects, the need to combine condom use with PrEP, and for regular HIV testing. Across populations, route of administration was considered the most important attribute of the presented alternatives. CONCLUSIONS: Despite multiple conceivable barriers, there was a general willingness to adopt PrEP in key populations, which suggests that if efficacious and affordable, it could be a useful tool in HIV prevention. There would be a willingness to experience inconvenience and expense at the levels included in the survey. The results suggest that delivery in a long lasting injection would be a good target in drug development

Civil society leadership in the struggle for AIDS treatment in South Africa and Uganda

Includes abstract.Includes bibliographical references.This thesis is an attempt to theorise and operationalise empirically the notion of ‘civil society leadership’ in Sub-Saharan Africa. ‘AIDS leadership,’ which is associated with the intergovernmental institutions charged with coordinating the global response to HIV/AIDS, is both under-theorised and highly context-specific. In this study I therefore opt for an inclusive framework that draws on a range of approaches, including the literature on ‘leadership’, institutions, social movements and the ‘network’ perspective on civil society mobilisation. This framework is employed in rich and detailed empirical descriptions (‘thick description’) of civil society mobilisation around AIDS, including contentious AIDS activism, in the key case studies of South Africa and Uganda. South Africa and Uganda are widely considered key examples of poor and good leadership (from national political leaders) respectively, while the Treatment Action Campaign (TAC) and The AIDS Support Organisation (TASO) are both seen as highly effective civil society movements. These descriptions emphasise ‘transnational networks of influence’ in which civil society leaders participated (and at times actively constructed) in order to mobilise both symbolic and material resources aimed at exerting influence at the transnational, national and local levels

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

___Key messages___ The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer

Views of policymakers, healthcare workers and NGOs on HIV pre-exposure prophylaxis (PrEP): a multinational qualitative study.

OBJECTIVES: To examine policymakers and providers' views on pre-exposure prophylaxis (PrEP) and their willingness to support its introduction, to inform policy and practice in this emerging field. DESIGN: Semistructured qualitative interview study. SETTING: Peru, Ukraine, India, Kenya, Uganda, Botswana and South Africa. PARTICIPANTS: 35 policymakers, 35 healthcare workers and 21 non-governmental organisation representatives involved in HIV prevention. RESULTS: Six themes emerged from the data: (1) perceived HIV prevention landscape: prevention initiatives needed to be improved and expanded; (2) PrEP awareness: 50 of 91 participants had heard of PrEP; (3) benefits of PrEP: one component of the combination prevention arsenal that could help prioritise HIV prevention, empower key populations and result in economic gains; (4) challenges of PrEP: regimen complexity, cost and cost-effectiveness, risk compensation, efficacy and effectiveness, stigmatisation and criminalisation, information and training and healthcare system capacity; (5) programmatic considerations: user eligibility, communication strategy, cost, distribution, medication and HIV testing compliance and (6) early versus late implementation: participants were divided as to whether they would support an early introduction of PrEP in their country or would prefer to wait until it has been successfully implemented in other countries, with around half of those we spoke to supporting each option. Very few said they would not support PrEP at all. CONCLUSIONS: Despite the multiple challenges identified, there was general willingness to support the introduction of PrEP. Yet, strengthening existing HIV prevention efforts was also deemed necessary. Our results suggest that an effective PrEP programme would be delivered in healthcare facilities and involve non-governmental organisations and the community and consider the needs of mobile populations. Comprehensive information packages and training for users and providers would be critical. The cost of PrEP would be affordable and possibly segmented. Extensive counselling and innovative monitoring measures ought to be considered

Participants' characteristics and likelihood of PrEP use.

**<p>Correlation significant at .01 level.</p><p>*Correlation significant at .05 level (2-tailed).</p><p>Numbers in the column headings represent the characteristics enumerated in the row headings.</p