Informing Comprehensive HIV Prevention: A Situational Analysis of the HIV Prevention and Care Context,North West Province South Africa

Objective

Building a successful combination prevention program requires understanding the community’s local epidemiological profile, the social community norms that shape vulnerability to HIV and access to care, and the available community resources. We carried out a situational analysis in order to shape a comprehensive HIV prevention program that address local barriers to care at multiple contextual levels in the North West Province of South Africa.

Method

The situational analysis was conducted in two sub-districts in 2012 and guided by an adaptation of WHO’s Strategic Approach, a predominantly qualitative method, including observation of service delivery points and in-depth interviews and focus groups with local leaders, providers, and community members, in order to recommend context-specific HIV prevention strategies. Analysis began during fieldwork with nightly discussions of findings and continued with coding original textual data from the fieldwork notebooks and a select number of recorded interviews.

Results

We conducted over 200 individual and group interviews and gleaned four principal social barriers to HIV prevention and care, including: HIV fatalism, traditional gender norms, HIV-related stigma, and challenges with communication around HIV, all of which fuel the HIV epidemic. At the different levels of response needed to stem the epidemic, we found evidence of national policies and programs that are mitigating the social risk factors but little community-based responses that address social risk factors to HIV.

Conclusions

Understanding social and structural barriers to care helped shape our comprehensive HIV prevention program, which address the four ‘themes’ identified into each component of the program. Activities are underway to engage communities, offer community-based testing in high transmission areas, community stigma reduction, and a positive health, dignity and prevention program for stigma reduction and improve communication skills. The situational analysis process successfully shaped key programmatic decisions and cultivated a deeper collaboration with local stakeholders to support program implementation.     

Synergism between fungal enzymes and bacterial antibiotics may enhance biocontrol

The interactions between biocontrol fungi and bacteria may play a key role in the natural process of biocontrol, although the molecular mechanisms involved are still largely unknown. Synergism can occur when different agents are applied together, and cell wall degrading enzymes (CWDEs) produced by fungi can increase the efficacy of bacteria. Pseudomonas spp. produce membrane-disrupting lipodepsipeptides (LDPs) syringotoxins (SP) and syringomycins (SR). SR are considered responsible for the antimicrobial activity, and SP for the phytotoxicity. CWDEs of Trichoderma spp. synergistically increased the toxicity of SP_25-A or SR_E purified from P. syringae against fungal pathogens. For instance, the fungal enzymes made Botrytis cinerea and other phytopathogenic fungi, normally resistant to SP_25-A alone, more susceptible to this antibiotic. Pseudomonas produced CWDEs in culture conditions that allow the synthesis of the LDPs. Purified bacterial enzymes and metabolites were also synergistic against fungal pathogens, although this mixture was less powerful than the combination with the Trichoderma CWDEs. The positive interaction between LDPs and CWDEs may be part of the biocontrol mechanism in some Pseudomonas strains, and co-induction of different antifungal compounds in both biocontrol bacteria and fungi may occur. This revised version was published online in August 2006 with corrections to the Cover Date.     

Gender inequity norms are associated with increased male-perpetrated rape and sexual risks for HIV infection in Botswana and Swaziland

Background

There is limited empirical research on the underlying gender inequity norms shaping gender-based violence, power, and HIV risks in sub-Saharan Africa, or how risk pathways may differ for men and women. This study is among the first to directly evaluate the adherence to gender inequity norms and epidemiological relationships with violence and sexual risks for HIV infection.

Methods

Data were derived from population-based cross-sectional samples recruited through two-stage probability sampling from the 5 highest HIV prevalence districts in Botswana and all districts in Swaziland (2004–5). Based on evidence of established risk factors for HIV infection, we aimed 1) to estimate the mean adherence to gender inequity norms for both men and women; and 2) to model the independent effects of higher adherence to gender inequity norms on a) male sexual dominance (male-controlled sexual decision making and rape (forced sex)); b) sexual risk practices (multiple/concurrent sex partners, transactional sex, unprotected sex with non-primary partner, intergenerational sex).

Findings

A total of 2049 individuals were included, n = 1255 from Botswana and n = 796 from Swaziland. In separate multivariate logistic regression analyses, higher gender inequity norms scores remained independently associated with increased male-controlled sexual decision making power (AORmen = 1.90, 95%CI:1.09–2.35; AORwomen = 2.05, 95%CI:1.32–2.49), perpetration of rape (AORmen = 2.19 95%CI:1.22–3.51), unprotected sex with a non-primary partner (AORmen = 1.90, 95%CI:1.14–2.31), intergenerational sex (AORwomen = 1.36, 95%CI:1.08–1.79), and multiple/concurrent sex partners (AORmen = 1.42, 95%CI:1.10–1.93).

Interpretation

These findings support the critical evidence-based need for gender-transformative HIV prevention efforts including legislation of women''s rights in two of the most HIV affected countries in the world.     

Genetic transfer of clumping phenotype inAnacystis nidulans

Occasionally a mutation occurs in liquid cultures ofAnacystis nidulans, spreading quickly through the population and causing cells to adhere together in clumps. This phenotype is stable indefinitely and is an inherited characteristic of all cells within a clumping culture. Inoculation with a few living cells from a clumping culture quickly produces the clumping genotype in a majority of cells within a previously non-clumping culture. Killed cells, broken cell extracts, or media from clumping cultures do not produce aggregation in non-clumping cultures. Actively growing cells in clumping cultures do not affect non-clumping cultures when separated by 0.4 μm Millipore filter. Apparently transfer of the clumping trait requires direct contact between living cells. Pili-like projections connect individual cells within clumps, but no slime layer or capsule is seen. Clumps can be dispersed without cell damage; reaggregation requires photosynthesis.     

Membrane and protein properties of freeze-dried mouse platelets

Membrane properties and the overall protein secondary structure of freeze-dried trehalose-loaded mouse platelets were studied using steady state fluorescence anisotropy and Fourier transform infrared spectroscopy (FTIR). FTIR results showed that fresh control mouse platelets have a main phase transition at ~14°C, whereas, freeze-dried platelets exhibited a main phase transition ~12°C. However, the cooperativity of the transition of the rehydrated platelets was greatly enhanced compared to that of control platelets. Anisotropy experiments performed with 1,6 diphenyl-1,3,5 hexatriene (DPH) complemented FTIR results and showed that the lipid order in the core of the membrane was affected by freeze-drying procedures. Similar experiments with trimethyl ammonium 1,6 diphenyl-1,3,5 hexatriene (TMA-DPH), a membrane surface probe, indicated that membrane properties at the membrane/water interface were less affected by freeze-drying procedures than the core of the membrane. Lyophilization did not result in massive protein denaturation, but the overall protein secondary structure was altered, based on in situ assessment of the amide-I and amide-II band profiles. Lyophilization-induced changes to endogenous platelet proteins were further investigated by studying the protein's heat stability. In fresh control platelets, proteins denatured at 42°C, whereas proteins in the rehydrated platelets denatured at 48°C.     

A neural systems analysis of adaptive navigation

In the field of the neurobiology of learning, significant emphasis has been placed on understanding neural plasticity within a single structure (or synapse type) as it relates to a particular type of learning mediated by a particular brain area. To appreciate fully the breadth of the plasticity responsible for complex learning phenomena, it is imperative that we also examine the neural mechanisms of the behavioral instantiation of learned information, how motivational systems interact, and how past memories affect the learning process. To address this issue, we describe a model of complex learning (rodent adaptive navigation) that could be used to study dynamically interactive neural systems. Adaptive navigation depends on the efficient integration of external and internal sensory information with motivational systems to arrive at the most effective cognitive and/or behavioral strategies. We present evidence consistent with the view that during navigation: 1) the limbic thalamus and limbic cortex is primarily responsible for the integration of current and expected sensory information, 2) the hippocampal-septal-hypothalamic system provides a mechanism whereby motivational perspectives bias sensory processing, and 3) the amygdala-prefrontal-striatal circuit allows animals to evaluate the expected reinforcement consequences of context-dependent behavioral responses. Although much remains to be determined regarding the nature of the interactions among neural systems, new insights have emerged regarding the mechanisms that underlie flexible and adaptive behavioral responses.     

Synthesis and biological activity of piperazine-based dual MMP-13 and TNF-alpha converting enzyme inhibitors

A series of novel MMP-13 and TNF-alpha converting enzyme inhibitors based on piperazine 2-hydroxamic acid scaffolds are described. The TACE, MMP-1 and MMP-13 activity of these inhibitors as well as the effect of substitution of the piperazine nitrogen and the P-1' benzyloxy tailpiece is discussed. Moderate in vivo activity is observed with several members of this group.     

Aminopyridinecarboxamide-based inhibitors: Structure–activity relationship

Series of aminopyridinecarboxamide-based inhibitors were synthesized and tested against human recombinant IKK-2 and in IL-1β stimulated synovial fibroblasts. The 2-amino-5-chloropyridine-4-carboxamides were identified as the most potent inhibitors with improved cellular activity.     

Functional complementation between the PDX1 vitamin B6 biosynthetic gene of Cercospora nicotianae and pdxJ of Escherichia coli

The pathway for de novo vitamin B(6) biosynthesis has been characterized in Escherichia coli, however plants, fungi, archaebacteria, and most bacteria utilize an alternative pathway. Two unique genes of the alternative pathway, PDX1 and PDX2, have been described. PDX2 encodes a glutaminase, however the enzymatic function of the product encoded by PDX1 is not known. We conducted reciprocal transformation experiments to determine if there was functional homology between the E. coli pdxA and pdxJ genes and PDX1 of Cercospora nicotianae. Although expression of pdxJ and pdxA in C. nicotianae pdx1 mutants, either separately or together, failed to complement the pyridoxine mutation in this fungus, expression of PDX1 restored pyridoxine prototrophy to the E. coli pdxJ mutant. Expression of PDX1 in the E. coli pdxA mutant restored very limited ability to grow on medium lacking pyridoxine. We conclude that the PDX1 gene of the alternative B(6) pathway encodes a protein responsible for synthesis of the pyridoxine ring.