Structural approaches for prevention of sexually transmitted HIV in general populations: definitions and an operational approach.

INTRODUCTION: Although biomedical HIV prevention efforts have seen a number of recent promising developments, behavioural interventions have often been described as failing. However, clear lessons have been identified from past efforts, including the need to address influential social, economic and legal structures; to tailor efforts to local contexts; and to address multiple influencing factors in combination. Despite these insights, there remains a pervasive strategy to try to achieve sexual behaviour change through single, decontextualized, interventions or sets of activities. With current calls for structural approaches to HIV as part of combination HIV prevention, though, there is a unique opportunity to define a structural approach to HIV prevention as one which moves beyond these past limitations and better incorporates our knowledge of the social world and the lessons from past efforts. DISCUSSION: A range of interlinked concepts require delineation and definition within the broad concept of a structural approach to HIV. This includes distinguishing between "structural factors," which can be seen as any number of elements (other than knowledge) which influence risk and vulnerability, and "structural drivers," which should be reserved for situations where an empirically established relationship to a target group is known. Operationalizing structural approaches similarly can take different paths, either working to alter structural drivers or alternatively working to build individual and community resilience to infection. A "structural diagnostic approach" is further defined as the process one undertakes to develop structural intervention strategies tailored to target groups. CONCLUSIONS: For three decades, the HIV prevention community has struggled to reduce the spread of HIV through sexual risk behaviours with limited success, but equally with limited engagement with the lessons that have been learned about the social realities shaping patterns of sexual practices. Future HIV prevention efforts must address the multiple factors influencing risk and vulnerability, and they must do so in ways tailored to particular settings. Clarity on the concepts, terminology and approaches that can allow structural HIV prevention efforts to achieve this is therefore essential to improve the (social) science of HIV prevention

Key informant perspectives on policy- and service-level challenges and opportunities for delivering integrated sexual and reproductive health and HIV care in South Africa

BACKGROUND: Integration of sexual and reproductive health (SRH) and HIV services is a policy priority, both globally and in South Africa. Recent studies examining SRH/HIV integration in South Africa have focused primarily on the SRH needs of HIV patients, and less on the policy and service-delivery environment in which these programs operate. To fill this gap we undertook a qualitative study to elicit the views of key informants on policy-and service-level challenges and opportunities for improving integrated SRH and HIV care in South Africa. This study comprised formative research for the development of an integrated service delivery model in KwaZulu-Natal (KZN) Province. METHODS: Semi-structured in-depth interviews were conducted with 21 expert key informants from the South African Department of Health, and local and international NGOs and universities. Thematic codes were generated from a subset of the transcripts, and these were modified, refined and organized during coding and analysis. RESULTS: While there was consensus among key informants on the need for more integrated systems of SRH and HIV care in South Africa, a range of inter-related systems factors at policy and service-delivery levels were identified as challenges to delivering integrated care. At the policy level these included vertical programming, lack of policy guidance on integrated care, under-funding of SRH, program territorialism, and weak referral systems; at the service level, factors included high client load, staff shortages and insufficient training and skills in SRH, resistance to change, and inadequate monitoring systems related to integration. Informants had varying views on the best way to achieve integration: while some favored a one-stop shop approach, others preferred retaining sub-specialisms while strengthening referral systems. The introduction of task-shifting policies and decentralization of HIV treatment to primary care provide opportunities for integrating services. CONCLUSION: Now that HIV treatment programs have been scaled up, actions are needed at both policy and service-delivery levels to develop an integrated approach to the provision of SRH and HIV services in South Africa. Concurrent national policies to deliver HIV treatment within a primary care context can be used to promote more integrated approaches

Increasing Support for Contraception as HIV Prevention: Stakeholder Mapping to Identify Influential Individuals and Their Perceptions

BACKGROUND: Voluntary contraceptive use by HIV-positive women currently prevents more HIV-positive births, at a lower cost, than anti-retroviral drug (ARV) regimens. Despite this evidence, most prevention of mother-to-child transmission (PMTCT) programs focus solely on providing ARV prophylaxis to pregnant women and rarely include the prevention of unintended pregnancies among HIV-positive women. METHODOLOGY/PRINCIPAL FINDINGS: To strengthen support for family planning as HIV prevention, we systematically identified key individuals in the field of international HIV/AIDS-those who could potentially influence the issue-and sought to determine their perceptions of barriers to and facilitators for implementing this PMTCT strategy. We used a criteria-based approach to determine which HIV/AIDS stakeholders have the most significant impact on HIV/AIDS research, programs, funding and policy and stratified purposive sampling to conduct interviews with a subset of these individuals. The interview findings pointed to obstacles to strengthening linkages between family planning and HIV/AIDS, including the need for: resources to integrate family planning and HIV services, infrastructure or capacity to provide integrated services at the facility level, national leadership and coordination, and targeted advocacy to key decision-makers. CONCLUSIONS/SIGNIFICANCE: The individuals we identified as having regional or international influence in the field of HIV/AIDS have the ability to leverage an increasingly conducive funding environment and a growing evidence base to address the policy, programmatic and operational challenges to integrating family planning with HIV/AIDS. Fostering greater support for implementing contraception for HIV prevention will require the dedication, collaboration and coordination of many such actors. Our findings can inform a targeted advocacy campaign

High Incidence of Unplanned Pregnancy after Antiretroviral Therapy Initiation: Findings from a Prospective Cohort Study in South Africa

Increased fertility rates in HIV-infected women receiving antiretroviral therapy (ART) have been attributed to improved immunological function; it is unknown to what extent the rise in pregnancy rates is due to unintended pregnancies.Non-pregnant women ages 18-35 from four public-sector ART clinics in Johannesburg, South Africa, were enrolled into a prospective cohort and followed from August 2009-March 2011. Fertility intentions, contraception and pregnancy status were measured longitudinally at participants' routine ART clinic visits.Of the 850 women enrolled, 822 (97%) had at least one follow-up visit and contributed 745.2 person-years (PY) at-risk for incident pregnancy. Overall, 170 pregnancies were detected in 161 women (incidence rate [IR]: 21.6/100 PY [95% confidence interval (CI): 18.5-25.2]). Of the 170 pregnancies, 105 (62%) were unplanned. Unmet need for contraception was 50% higher in women initiating ART in the past year as compared to women on ART>1 year (prevalence ratio 1.5 [95% CI: 1.1-2.0]); by two years post-ART initiation, nearly one quarter of women had at least one unplanned pregnancy. Cumulative incidence of pregnancy was equally high among recent ART initiators and ART experienced participants: 23.9% [95% CI: 16.4-34.1], 15.9% [12.0-20.8], and 21.0% [16.8-26.1] for women on ART 0-1 yr, >1 yr-2 yrs, and >2 yrs respectively (log-rank, p = 0.54). Eight hormonal contraceptive failures were detected [IR: 4.4 [95% CI: 2.2-8.9], 7/8 among women using injectable methods. Overall 47% (80/170) of pregnancies were not carried to term.Rates of unintended pregnancies among women on ART are high, including women recently initiating ART with lower CD4 counts and higher viral loads. A substantial burden of pregnancy loss was observed. Integration of contraceptive services and counselling into ART care is necessary to reduce maternal and child health risks related to mistimed and unwanted pregnancies. Further research into injectable contraceptive failures on ART is warranted

Outputs, cost and efficiency of public sector centres for prevention of mother to child transmission of HIV in Andhra Pradesh, India

<p>Abstract</p> <p>Background</p> <p>Prevention of mother to child transmission (PMTCT) is an important part of the effort to control HIV. PMTCT services are mostly provided at public sector government hospitals in India. Systematic data on the cost and efficiency of providing PMTCT services in India are not available readily for further planning.</p> <p>Methods</p> <p>Cost and output data were collected at 16 sampled PMTCT centres in the south Indian state of Andhra Pradesh using standardized methods. The services provided were analysed, and the relation of unit cost of services with scale was assessed.</p> <p>Results</p> <p>In the 2005–2006 fiscal year, 125,073 pregnant women received PMTCT services at the 16 centres (range 2,939 to 20,896, median 5,679). The overall HIV positive rate among those tested was 1.67%. Of the total economic cost, the major components were personnel (47.3%) and recurrent goods (31.7%). For the 16 PMTCT centres, the average economic cost per post-HIV-test counselled pregnant woman was Indian Rupees (INR) 98.9 (US$2.23), ranging 2.7-fold from INR 71.4 (US$ 1.61) to INR 189.9 (US$4.29). The economic cost per mother-neonate pair who received nevirapine had a higher variation, ranging 41-fold for the 16 centres from INR 4,354 (US$ 98) to INR 179,175 (US$4,047), average INR 10,210 (US$ 231), with very high unit cost at some centres where HIV prevalence among pregnant women and the total volume of services were both low. Scale had a significant inverse relation with both of the unit costs, per post-HIV-test counselled pregnant woman and per mother-neonate pair who received nevirapine. In addition, HIV prevalence among pregnant women had a significant inverse relation with unit cost per mother-neonate pair who received nevirapine.</p> <p>Conclusion</p> <p>Although the variation between PMTCT centres for unit cost per post-HIV-test counselled pregnant woman was modest that per mother-neonate pair receiving nevirapine was over 40-fold. The extremely high unit cost for each mother-neonate pair receiving nevirapine at some centres suggests that the new approach of combining PMTCT services with voluntary counselling and testing services that has recently been started in India could potentially offer better efficiency.</p

Tipping the Balance: Sclerotinia sclerotiorum Secreted Oxalic Acid Suppresses Host Defenses by Manipulating the Host Redox Environment

Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with an extremely broad host range. This pathogen produces the non-specific phytotoxin and key pathogenicity factor, oxalic acid (OA). Our recent work indicated that this fungus and more specifically OA, can induce apoptotic-like programmed cell death (PCD) in plant hosts, this induction of PCD and disease requires generation of reactive oxygen species (ROS) in the host, a process triggered by fungal secreted OA. Conversely, during the initial stages of infection, OA also dampens the plant oxidative burst, an early host response generally associated with plant defense. This scenario presents a challenge regarding the mechanistic details of OA function; as OA both suppresses and induces host ROS during the compatible interaction. In the present study we generated transgenic plants expressing a redox-regulated GFP reporter. Results show that initially, Sclerotinia (via OA) generates a reducing environment in host cells that suppress host defense responses including the oxidative burst and callose deposition, akin to compatible biotrophic pathogens. Once infection is established however, this necrotroph induces the generation of plant ROS leading to PCD of host tissue, the result of which is of direct benefit to the pathogen. In contrast, a non-pathogenic OA-deficient mutant failed to alter host redox status. The mutant produced hypersensitive response-like features following host inoculation, including ROS induction, callose formation, restricted growth and cell death. These results indicate active recognition of the mutant and further point to suppression of defenses by the wild type necrotrophic fungus. Chemical reduction of host cells with dithiothreitol (DTT) or potassium oxalate (KOA) restored the ability of this mutant to cause disease. Thus, Sclerotinia uses a novel strategy involving regulation of host redox status to establish infection. These results address a long-standing issue involving the ability of OA to both inhibit and promote ROS to achieve pathogenic success

Impact of Antiretroviral Therapy on Incidence of Pregnancy among HIV-Infected Women in Sub-Saharan Africa: A Cohort Study

A multicountry cohort study in sub-Saharan Africa by Landon Myer and colleagues reveals higher pregnancy rates in HIV-infected women on antiretroviral therapy (ART)

Focus on collagen: in vitro systems to study fibrogenesis and antifibrosis _ state of the art

Fibrosis represents a major global disease burden, yet a potent antifibrotic compound is still not in sight. Part of the explanation for this situation is the difficulties that both academic laboratories and research and development departments in the pharmaceutical industry have been facing in re-enacting the fibrotic process in vitro for screening procedures prior to animal testing. Effective in vitro characterization of antifibrotic compounds has been hampered by cell culture settings that are lacking crucial cofactors or are not holistic representations of the biosynthetic and depositional pathway leading to the formation of an insoluble pericellular collagen matrix. In order to appreciate the task which in vitro screening of antifibrotics is up against, we will first review the fibrotic process by categorizing it into events that are upstream of collagen biosynthesis and the actual biosynthetic and depositional cascade of collagen I. We point out oversights such as the omission of vitamin C, a vital cofactor for the production of stable procollagen molecules, as well as the little known in vitro tardy procollagen processing by collagen C-proteinase/BMP-1, another reason for minimal collagen deposition in cell culture. We review current methods of cell culture and collagen quantitation vis-à-vis the high content options and requirements for normalization against cell number for meaningful data retrieval. Only when collagen has formed a fibrillar matrix that becomes cross-linked, invested with ligands, and can be remodelled and resorbed, the complete picture of fibrogenesis can be reflected in vitro. We show here how this can be achieved. A well thought-out in vitro fibrogenesis system represents the missing link between brute force chemical library screens and rational animal experimentation, thus providing both cost-effectiveness and streamlined procedures towards the development of better antifibrotic drugs