Measuring Regional Policy Change and Pro-Poor Health Policy Success: A PRARI Toolkit of Indicators for the Southern African Development Community (SADC)

PRARI is a social development research project that looks at world-regional social governance, politics, and policy. PRARI brings together an international team of researchers studying the scope for enhancing the effectiveness of the contributions of Southern regional organisations to poverty reduction. It receives funding from the ESRC

The C3-V4 region is a major target of autologous neutralizing antibodies in human immunodeficiency virus type 1 subtype C Infection.

The early autologous neutralizing antibody response in human immunodeficiency virus type 1 (HIV-1) subtype C infections is often characterized by high titers, but the response is type specific with little to no cross-neutralizing activity. The specificities of these early neutralizing antibodies are not known; however, the type specificity suggests that they may target the variable regions of the envelope. Here, we show that cross-reactive anti-V3 antibodies developed within 3 to 12 weeks in six individuals but did not mediate autologous neutralization. Using a series of chimeric viruses, we found that antibodies directed at the V1V2, V4, and V5 regions contributed to autologous neutralization in some individuals, with V1V2 playing a more substantial role. However, these antibodies did not account for the total neutralizing capacity of these sera against the early autologous virus. Antibodies directed against the C3-V4 region were involved in autologous neutralization in all four sera studied. In two sera, transfer of the C3-V4 region rendered the chimera as sensitive to antibody neutralization as the parental virus. Although the C3 region, which contains the highly variable α2-helix was not a direct target in most cases, it contributed to the formation of neutralization epitopes as substitution of this region resulted in neutralization resistance. These data suggest that the C3 and V4 regions combine to form important structural motifs and that epitopes in this region are major targets of the early autologous neutralizing response in HIV-1 subtype C infection

Monitoring Pro-Poor Health-Policy Success in the SADC Region

Policy Conclusions Monitoring pro-poor health policies at the regional level can support both the countries and the regional bodies themselves by identifying gaps in addressing poverty and health, strengthening the link between regions and member states, holding actors accountable to their commitments and identifying better mechanisms for data sharing, monitoring and evaluation of activities. In the area of health, the Southern African Development Community (SADC) has conducted important work in understanding how poor health and poverty coincide, are mutually reinforcing, and socially-structured by gender, age, class, ethnicity and location, demonstrated by the key health policy documents that have been facilitated by the secretariat. Yet the time lapse between the formulation of guidelines and policies and their implementation has at times been uneven. The “Poverty Reduction and Regional Integration” (PRARI) project seeks to support the development of a monitoring system to measure the contribution of regional governance in the development of pro-poor health policies in collaboration with key stakeholders in the region. This system will build on existing efforts in the region and focus on policy areas such as the social determinants of health; HIV/AIDS, TB and malaria; non-communicable diseases; maternal and child health; human resources for health; pharmaceuticals; among others. Global developments such as those related to the incoming Sustainable Development Goals (SDGs) will also be considered. In order for this indicator-based monitoring system to be effective and to have an impact, it requires ‘regional ownership’, active participation of national and regional experts throughout the process of indicator development, implementation and evaluation, and evidence that it will be addressing health priorities for the region. For this, the institutional leadership from the SADC secretariat and the support from its Member States that are the main beneficiaries of the process is crucial. The strength of a regional body lies in the relevance that member-states see in it addressing their needs and managing the disparities between regional and national priorities. Monitoring existing processes would demonstrate the value-added by such integration efforts

Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, Griffithsin, Cyanovirin-N and Scytovirin.

Griffithsin (GRFT), Cyanovirin-N (CV-N) and Scytovirin (SVN) are lectins that inhibit HIV-1 infection by binding to multiple mannose-rich glycans on the HIV-1 envelope glycoproteins (Env). Here we show that these lectins neutralize subtype C primary virus isolates in addition to Env-pseudotyped viruses obtained from plasma and cervical vaginal lavages. Among 15 subtype C pseudoviruses, the median IC50 values were 0.4, 1.8 and 20.1 nM for GRFT, CV-N and SVN, respectively, similar to what was found for subtype B and A. Analysis of Env sequences suggested that concomitant lack of glycans at positions 234 and 295 resulted in natural resistance to these compounds, which was confirmed by site-directed mutagenesis. Furthermore, the binding sites for these lectins overlapped that of the 2G12 monoclonal antibody epitope, which is generally absent on subtype C Env. This data support further research on these lectins as potential microbicides in the context of HIV-1 subtype C infection

Genetic variation in gp 120 V1?V2 and neutralization sensitivity of HIV-1 subtype C isolates from children with rapid and slow disease progression

a dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg. for the Degree of Master of Science in Medicine (Virology) Johannesburg,. 2003This project explore genetic variation and antibody neutralization sensitivity in gp 120 V1/V2 and C2-V5 region amongst HIV-1 subtype C pediatric isolates. Isolates from 25 slow progressing children and 16 rapid progressing infants were used in subtyping and quasispecies analysis performed with a novel V1/V2 heteroduplex mobility assay (HMA)IT201

Voluntary medical male circumcision service delivery in South Africa: The economic costs and potential opportunity for private sector involvement.

BACKGROUND:In 2010, the South African Government initiated a voluntary medical male circumcision (VMMC) program as a part of the country's HIV prevention strategy based on compelling evidence that VMMC reduces men's risk of becoming HIV infected by approximately 60%. A previous VMMC costing study at Government and PEPFAR-supported facilities noted that the lack of sufficient data from the private sector represented a gap in knowledge concerning the overall cost of scaling up VMMC services. This study, conducted in mid-2016, focused on surgical circumcision and aims to address this limitation. METHODS:VMMC service delivery cost data were collected at 13 private facilities in three provinces in South Africa: Gauteng, KwaZulu-Natal, and Mpumalanga. Unit costs were calculated using a bottom-up approach by cost components, and then disaggregated by facility type and urbanization level. VMMC demand creation, and higher-level management and program support costs were not collected. The unit cost of VMMC service delivery at private facilities in South Africa was calculated as a weighted average of the unit costs at the 13 facilities. KEY FINDINGS:At the average annual exchange rate of R10.83 = $1, the unit cost including training and cost of continuous quality improvement (CQI) to provide VMMC at private facilities was$137. The largest cost components were consumables (40%) and direct labor (35%). Eleven out of the 13 surveyed private sector facilities were fixed sites (with a unit cost of $142), while one was a fixed site with outreach services (with a unit cost of$156), and the last one provided services at a combination of fixed, outreach and mobile sites (with a unit cost per circumcision performed of $123). The unit cost was not substantially different based on the level of urbanization:$141, $129, and$143 at urban, peri-urban, and rural facilities, respectively. CONCLUSIONS:The private sector VMMC unit cost ($137) did not differ substantially from that at government and PEPFAR-supported facilities ($132 based on results from a similar study conducted in 2014 in South Africa at 33 sites across eight of the countries nine provinces). The two largest cost drivers, consumables and direct labor, were comparable across the two studies (75% in private facilities and 67% in public/PEPFAR-supported facilities). Results from this study provide VMMC unit cost data that had been missing and makes an important contribution to a better understanding of the costs of VMMC service delivery, enabling VMMC programs to make informed decisions regarding funding levels and scale-up strategies for VMMC in South Africa

Acquisition of Polyfunctionality by Epstein-Barr Virus-Specific CD8+ T Cells Correlates with Increased Resistance to Galectin-1-Mediated Suppression▿

Latent membrane antigen 1 and -2 (LMP-1/2)-specific CD8+ T cells from newly diagnosed and relapsed Hodgkin's lymphoma (HL) patients display a selective functional impairment. In contrast, CD8+ T cells specific for Epstein-Barr virus (EBV) nuclear proteins and lytic antigens retain normal T-cell function. Reversion to a dysfunctional phenotype of LMP-1/2-specific T cells is coincident with the regression of HL. To delineate the potential basis for this differential susceptibility for the loss of function, we have carried out a comprehensive functional analysis of EBV-specific T cells using ex vivo multiparametric flow cytometry in combination with assessment of antigen-driven proliferative potential. This analysis revealed that LMP-1/2-specific T cells from healthy virus carriers display a deficient polyfunctional profile compared to that of T cells specific for epitopes derived from EBV nuclear proteins and lytic antigens. Furthermore, LMP-specific T-cells are highly susceptible to galectin-1-mediated immunosuppression and are less likely to degranulate following exposure to cognate peptide epitopes and poorly recognized endogenously processed epitopes from virus-infected B cells. More importantly, ex vivo stimulation of these T cells with an adenoviral vector encoding multiple minimal CD8+ T-cell epitopes as a polyepitope, in combination with a γC cytokine, interleukin-2, restored polyfunctionality and shielded these cells from the inhibitory effects of galectin-1