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Objective: Criminal liability for the sexual-transmission of HIV raises complex questions for both clinicians and service-users regarding their responsibilities and legal obligations to disclose information to others. This is the first research study to address the impact of these issues upon everyday clinical and professional management in the UK. The prevalence and incidence of clinical and HIV-legal issues reported by the 107 psychologists sampled are reported. Design: A cross-sectional approach comprising two components was utilised: Firstly, questionnaire survey (Response rate 22%) scoping the experiences of practice issues among psychologists from sexual-health and generic settings. Attitudes towards HIV-prosecutions and various measures of professional self-efficacy were also collected. Secondly, three focus groups (N=15) exploring the impact of practice issues upon clinicians’ likely confidentiality breaking behaviours. Methods: Clinical and legal issues are presented. Further statistical analyses explored the interaction of various demographic, clinical and attitudinal variables upon clinician’s perceived self-efficacy. Focus Group transcripts analysed using Thematic Analysis (Data-driven approach) with eight emergent themes. Results: Although no direct involvements in police investigations reported, two instances of psychology notes being subpoenaed plus multiple ‘near miss’ clinical experiences described. High proportions of sexual-health psychologists experienced HIV-clients disclosing problematic behaviours, including intentional transmission (9%; N=5) and/or ‘reckless’ behaviour (72%). Focus groups expressed high levels of anxiety regarding these scenarios associated to multiple influences (interpersonal, clinician, professional and service factors). Quantitative and qualitative results were triangulated to provide a detailed analysis of how psychologists manage the clinical impact of the issues. Conclusions: Psychologists broadly supported HIV-prosecutions for intentional transmission (81%) but only limited support around ‘reckless’ cases (44%), particularly among those sexual-health experienced. Those ‘critical’ attempted to mitigate the impact of legal issues by proactively raising awareness among HIV-clients and resisting overly-defensive service changes; whereas those ‘less-critical’ were more accepting. Clinical, training and therapeutic implications are briefly considered.

Objectives: To evaluate the prevalence of HIV-related misconceptions in an Outpatient Centre of Kinshasa (D.R.Congo) and analyze the association between these beliefs and HIV infection. Methods: A case-control study was carried out from December 2010 until June 2012. We assessed 1,630 participants aged 15-49 attending a primary outpatient centre in Kinshasa: 762 HIV Voluntary Counseling and Testing attendees and 868 blood donors. A 59-item questionnaire about knowledge, attitudes and practice was administered during a face-to-face interview, followed by an HIV test. Cases and controls were respondents with a newly diagnosed HIV positive or negative test, respectively. Unconditional logistic regression was used to analyse the association between misconceptions and HIV seropositivity. Results:Two hundred and seventy four cases and 1,340 controls were recruited. Cases were more likely than controls to have a low socioeconomic status, no education, to be divorced/separated or widowed. An association was found between the following variables and HIV-seropositivity: having a poor HIV knowledge (adjusted OR=2.79; 95%CI:1.43-5.45), not knowing a virus is the cause of AIDS (adjusted OR=2.03; 95%CI:1.38-2.98) and reporting more than three HIV-transmission-related misconceptions (adjusted OR=3.30; 95%CI:1.64-6.64), such as thinking an HIV+ person cannot look healthy and that HIV is transmitted by sorcery, God´s punishment, a kiss on the mouth, mosquitoes, coughs/sneezes or undercooked food. Conclusion:Despite having access to health care services, there are still many people in Kinshasa that have HIV-related misconceptions which increase their HIV risk. Our findings underscore the need for a culturally-adapted and gender-orientated basic HIV information into Congolese HIV prevention programs.

HIV-1 transmission is typically associated with the genetic bottleneck in which a single viral isolate, known as the transmitted/founder (T/F) virus, establishes successful infection in a new host. Current understanding of T/F virus properties is mostly limited to studies of envelope and very little is known about other post-entry viral properties. Here, T/F viruses from 3 successive generations of mother-to-child transmission (MTCT) were characterized. Nef mediated downregulation of human leukocyte antigen (HLA) class I and CD4, and Gag-Pol associated replication capacity appeared normal. Our results revealed no significant differences in these functions. The entry efficiency of T/F viruses and the maternal source were also similar however, the Envs of two maternal subsets varied in CD4 and CCR5 requirements for viral entry. Further understanding of whether there are unique functional characteristics of T/F viruses may perhaps provide an opportunity to design a vaccine or other intervention to prevent HIV-1 transmission.

The use of a measure of HIV transmission risk which incorporates seroadaptive behaviors is needed in order to assess the complex effects of disclosure on HIV transmission. The purpose of this study was to explore the use of a modified version of the ordinal scale of HIV risk behavior proposed by Osmond, Pollack, Paul, and Catania (2007) to operationalize the risk of HIV transmission among HIV-positive MSM and to establish the strength of the empirical evidence supporting the use of these scores for inference about HIV transmission. The original measure was modified to include the full potential for seropositioning (i.e., with and without 100% condom use) as a potential preventive strategy used by MSM to reduce the risk of HIV transmission. Additionally, the measure was applied to individual sexual encounters rather than globally so that the frequency of risk behaviors can be accurately modeled. The appropriateness of these methods was explored using data from a study involving the disclosure of serostatus to sexual partners in a sample of HIV-positive MSM. Results of the study are promising for the refinement of measurements of HIV transmission risk, and for the understanding of seroadaptive behavior in MSM. For researchers who are seeking to demonstrate the effectiveness of interventions designed to reduce HIV transmission risk, the ordinal measure provides a means for detecting qualitative shifts in sexual activity which can be critical to the question of effectiveness.

Many diseases in the aging population are associated with a class of peptide that aggregates to form amyloidogenic fibers through a misfolding from random coil, to cross β-sheet fibrils. Diseases such as Alzheimer’s disease, Parkinson’s disease, type II diabetes, and transmission of viral infection are shown to be linked to different amyloidogenic peptides. In two different projects within the amyloid field, we have chosen to study or amylin, in relation to type II diabetes, as well as a fragment of prostatic acid phosphatase (PAP248-286) whose fibrils have been termed a semen-derived enhancer of viral infection (SEVI). In relation to the amylin peptide, different aspects of the physiological storage conditions were probed. High concentrations of the peptide have proven very disruptive to membranes and very prone to aggregation in vitro, however in the secretory granule it is stored in mM concentrations. The three unique conditions to the granule are the relatively low pH (~6.0) and very high zinc (~14mM) and insulin (~4x amylin) concentrations. Here it is seen that separately, all three of these variables cause decreased membrane disruptive ability of amylin, and decreased ability to aggregate into amyloid fibers. Disruption of this environment such as lowered zinc concentrations could facilitate amylin’s membrane disruptive ability and further the progression of type II diabetes. We also characterized the relatively unstudied PAP248-286 peptide also an amyloid, and its interaction with model membrane systems to show that the peptide itself causes lipid aggregation and induces vesicle fusion, as would be the case for a peptide which facilitates the transmission of a virus. Yet while the monomeric shows fusiogenic activity, only the fibrillar form enhances viral transmission. The formation of these fibers is then critical to viral transmission. We see that the green tea compound EGCG can be used to both inhibit and disaggregate the amyloid fibers of SEVI due to its polyphenolic nature, while preformed fibrils of the E. coli produced curlin protein are seen to enhance the formation of SEVI. Cofactors such as the SEVI fibers could explain why HIV is weak in vitro, yet AIDS continues to be a global pandemic.

The control of the HIV epidemic is a momentous challenge. Despite successes in some situations, HIV transmission has not been adequately reduced by the HIV prevention methods currently available. This is demonstrated by the continuing spread of the HIV epidemic, mainly through sexual transmission. The approaches to HIV prevention have broadly been defined as structural, behavioural and biomedical. The objectives of this thesis were to examine the personal and public health impact of selected biomedical HIV prevention technologies on HIV acquisition and HIV risk behaviour and to explore a number of the specific scientific and methodological challenges encountered in the field of development of HIV prevention technologies. The following research aimed to add to the available Australian data on biomedical HIV prevention, and to determine the potential for future trials of HIV biomedical prevention in Australia. A number of key findings from this thesis contribute to knowledge in the area of biomedical HIV prevention research. Firstly, the design of published safety studies of candidate vaginal microbicides was not sufficient to detect potential toxic effects of these products. A second important contribution was the demonstration that there was no evidence of behavioural disinhibition after non-occupational post-exposure prophylaxis for HIV (NPEP) use. Thirdly, NPEP had an important protective effect against HIV acquisition at an individual level but not at a population level. Fourth, groups with high HIV incidence could be readily identified in low HIV incidence settings. Finally, men with higher levels of HIV risk were more willing to participate in clinical trials of biomedical HIV prevention technologies. The research in this thesis underlines the complex nature of biomedical HIV prevention research and HIV prevention implementation, from the design of clinical trials of candidate biomedical HIV prevention products, to identifying suitable study populations who are willing to take part in such trials and finally to implementing the use of such technologies. HIV prevention remains a global public health priority and it is imperative that efforts to identify safe and effective biomedical HIV prevention technologies continue.

The Effect of HIV-1 Subtypes on HIV Transmission and Disease Progression in Rakai District, Uganda Objectives: To determine whether HIV transmission and disease progression differ by HIV-1 subtype. Methods: The effect of HIV-1 subtypes on HIV transmission and disease progression was investigated using data from community-based cohort studies in Rakai district, Uganda. HIV-1 subtype was determined by genomic sequencing of the gag and gp41 viral regions and by the Multi-region Hybridization Assay (MHA). HIV viral loads were determined by Roche Amplicor v1.5, and CD4+ T cell counts by BD Facscalibur system. Adjusted measures of association were estimated using Poisson regression model, linear mixed effects model, and Cox proportional hazards model. Results: Adjusting for age, viral load, and genital ulcers (GUD), HIV transmission was higher for subtype A relative subtype D (Rate ratio, 1.98; 95% CI, 1.17 - 3.34). Age ( Conclusions: In Rakai, subtype A has a higher rate of HIV transmission than subtype D or inter-subtype recombinants. However, subtype A has a slower rate of progression to AIDS compared to subtype D, recombinants, and multiple HIV strains. Determination of HIV-1 subtype may be important in trials of preventive and therapeutic HIV-1 vaccines and in the management of HIV infected individuals.

The majority of Americans view AIDS as the most important health problem faced today. Despite efforts to educate the public, the literature suggests that misperceptions exist concerning HIV transmission. The documented case of a Florida dentist who transmitted the HIV virus to five dental patients focused the public's attention on its perceived vulnerability to contracting HIV during a dental visit. The purpose' of this descriptive study was to identify the dental patient's perceived risk of acquiring the AIDS virus during a dental visit and to then determine whether the perceived risk was related to the patient's level of oral hygiene. A convenience sample of 105 dental patients was assessed for level of oral hygiene and then completed a 25-item close-ended questionnaire. The results indicated that significant relationships existed between the patient's cumulative perceived risk of acquiring HIV during a dental visit and cumulative knowledge about the disease and education level. There was borderline significance in the relationship between perceived risk and level of oral hygiene.