Thesis (MPhil)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: In the light of the roll-out of the national combined school-health program which will include the availability of condoms to learners, this study was undertaken to determine what the perceptions of learners and educators are regarding the provision of condoms to learners at Malibu High School in Eerste River, Cape Town as a prevention strategy. The learners’ knowledge levels on HIV and AIDS were also tested. Questionnaires were handed out to learners as well as Life Orientation educators. The findings of the study revealed that the learners’ knowledge levels on HIV and AIDS are reasonably high and that parents are more involved as originally perceived to be. Learners seem to think that the provision of condoms by schools is a good idea. The educators’ views differ. The educators feel that the knowledge levels are low and that there is no visible parental or community involvement regarding HIV and AIDS. They see this as separate to their function. Educators are unanimous in their response that the provision of condoms by schools is not a good idea at all. They feel that it would send out the wrong message to learners. From the study, it became apparent that the Education department still needs to do a lot to get schools on board for the roll-out of the school-health program. A lot needs to be done regarding the training of and support to the educators. A few recommendations are listed in order for the school to effectively address the HIV and AIDS issues at the school in order to reduce its impact. / AFRIKAANSE OPSOMMING: Die toekomstige uitrol van die nasionale gekombineerde skole-gesondheidsprogram sluit die verskaffing van kondome aan leerders in. Hierdie studie was dus hiervolgens onderneem om juis uit te vind wat die persepsies van leerders sowel as die opvoeders van Malibu Hoërskool in Eersterivier, Kaapstad is rakende die verskaffing van kondome aan leerders. Die leerders se kennisvlakke rakende MIV en VIGS was ook getoets. Vraelyste was uitgehandig aan beide die leerders en die Lewensoriëntering-opvoeders. Die bevindinge van die studie weerspiëel egter dat die kennisvlakke van leerders taamlik hoog is en dat ouers eitlik meer betrokke is as wat aanvanklik waargeneem was. Leerders is van mening dat die voorsiening van kondome aan hulle deur skole eintlik ‘n goeie idée is. Die opvoeders se menings verskil egter. Die opvoeders is van mening dat die leerders se kennisvlakke laag is en dat daar egter geen sigbare ouer- en gemeenskapsbetrokkenheid bestaan nie. Opvoeders sien hierdie as apart van hul opvoedingsfunksie. Opvoeders voel dat die verskaffing van kondome aan leerders by skole nie ‘n goeie idée is nie. Volgens hulle sal dit egter die verkeerde boodskap aan leerders deurgee. Volgens die bevindinge van die studie is dit dus baie duidelik dat die Onderwysdepartement nóg baie moet doen om skole aan boord te kry rakende die uitrol van die skole-gesondheidsprogram. Baie moet gedoen word rakende die opleiding van en ondersteuning aan opvoeders in hierdie verband. ‘n Paar aanbevelings word voorgelê om die skool in staat te stel om die MIV en VIGS-kwessies effektief aan te spreek om sodoende die impak daarvan by die skool te verminder.

Background: Literature has shown that negative attitudes and unwillingness to care for HIV-infected patients are prevailing among healthcare workers. This study aimed to assess the attitudes and willingness of student nurses towards caring for HIV-infected patients in some public hospitals in Gert Sibande district, Mpumalanga. Method: A contextual exploratory quantitative descriptive survey was conducted among student nurses enrolled for a four-year nursing qualification in a nursing college at Mpumalanga province. Self-administered questionnaires were completed after obtaining an informed consent. Results: A total of 122 (70.9%) students participated in this survey. Findings showed that most participants had positive attitudes 66 (52.7%) and were willing 121 (99.1%) to care for HIV-infected patients. Significant associations were revealed between participants’ previous HIV testing (p=0.012), age group (p=0.009), and their willingness to provide care to HIV-infected patients. Conclusion: Results showed a generally positive attitude and willingness by participants to care for HIV-infected patients. / Health Studies / M.A. (Health Studies)

Power imbalances and gender-based violence (GBV) have increasingly been cited as important determinants putting women at risk of HIV infections. Studies have shown that globally one in every three women has been beaten, coerced into sex or otherwise abused in her lifetime. The study explored working women’s perceptions of power, gender-based violence and HIV-infection risks. A qualitative, explorative study was conducted among female employees in an airline business in Namibia. Five women participated in in-depth, face-to-face interviews. The findings show that all of the participants experienced power imbalances and GBV in their intimate relationships. All of the women reported emotional or psychological abuse, whilst the majority were subjected to economic abuse, followed by physical abuse, and two alleged having been sexually abused. The study concludes with specific recommendations for the development and successful implementation of workplace policy and programmes to protect and promote women’s rights. / Social Work / M.A. (Social Behaviour Studies in HIV/AIDS)

The purpose of the study was to evaluate the IMB skills model for its relevance to the Ethiopian context. According to the model, adherence-related information and motivation work through adherence-related behavioural skills to affect adherence to ART. Quantitative, analytical, observational, cross-sectional, institution-based study was conducted to evaluate the model by assessing those patients who have and do not have the right information, motivation, and behavioural skills whether they have or do not have good adherence to ART. Data was collected using structured questionnaires where a total of 400 randomly selected participants provided data on adherence-related information, motivation and behavioral skills as well as adherence behavior per se. Data was analysed using the Statistical Package for Social Sciences (SPSS) version 20.0. Both descriptive and inferential statistics used in the study. Only 90.75 % of the total sample population reported ART adherence rate of more than or equal to 95% in this study. Free and restricted model tests, through bivariate and multivariate analyses, used to assess the propositions of the IMB model of ART adherence and provided support for the interrelations between the elements proposed by the model. The study has supported the applicability of the IMB model of adherence to the Ethiopian context highlighting its application in adherence-promotion intervention efforts. The findings revealed the need for on-going educational, informational and other interventions to address the knowledge, motivation and adherence behavioural skills of patients in order to improve the current levels of ART adherence behaviour. / Health Studies / D. Litt. et Phil. (Health Studies)

Introdução: A associação entre a infecção pelo vírus da imunodeficiência humana (HIV) e o câncer tem sido documentada desde os primórdios da epidemia da síndrome da imunodeficiência adquirida (Aids). A introdução da highly active antirretroviral therapy (HAART) alterou, profundamente, o curso da epidemia da Aids, reduzindo, drasticamente, a incidência de manifestações definidoras da síndrome, incluindo cânceres. No entanto, existem informações limitadas sobre a incidência de câncer em crianças e adolescentes com Aids vivendo em países em desenvolvimento. Objetivo: Descrever a epidemiologia do câncer em crianças e adolescentes com Aids no Município de São Paulo, no período de 1997 a 2012. Métodos: Trata-se de um estudo de base populacional, utilizando as bases de dados do Registro de Câncer de Base Populacional do Município de São Paulo e do Sistema de Informações de Agravos de Notificação (SINAN). As crianças e adolescentes (< 20 anos) com Aids e câncer foram identificadas por meio de um processo de linkage probabilístico entre as bases de dados supracitadas. Foram calculadas as taxas de incidência brutas e ajustadas por milhão de habitantes. Para comparar a incidência de câncer na população com Aids e a população geral foi calculada a razão de incidência padronizada (RIP) e respectivos intervalos de confiança de 95 por cento (IC 95 por cento ). A análise de tendência foi feita por meio do cálculo do annual percent change (APC) e IC 95 por cento correspondentes. A análise da sobrevida global de cinco anos após o câncer entre pacientes com Aids e na população geral foi calculada por meio do estimador produto limite de Kaplan-Meier e modelos univariados de riscos proporcionais de Cox. Mapas coropléticos em escalas monocromáticas foram gerados para descrever a distribuição de casos no Município. Resultados: Foram identificados 24 casos de câncer em pacientes com Aids menores de 20 anos, sendo 62,5 por cento cânceres definidores de Aids. Os cânceres mais incidentes foram o linfoma não Hodgkin, incluindo o linfoma de Burkitt (12; 50,0 por cento ), o linfoma de Hodgkin (6; 25,0 por cento ) e o sarcoma de Kaposi (3; 12,5 por cento ). A taxa bruta de incidência foi de 1.461,3 casos/milhão. A análise de tendência revelou redução significativa da incidência para todos os cânceres (APC= -14,5), influenciada pela queda nos cânceres definidores de Aids (APC= -17,0). O risco para câncer se mostrou aumentado (RIP= 3,9), sobretudo para o linfoma não Hodgkin, excluindo linfoma de Burkitt (RIP= 22,5), linfoma de Burkitt (RIP= 29,7) e linfoma de Hodgkin (RIP= 18,7). A probabilidade acumulada de sobrevida aos cinco anos foi de 56,3 por cento em crianças e adolescentes com Aids versus 87,5 por cento na população geral. A hazard ratio para óbito foi 5,2 (IC 95 por cento = 2,0; 13,6). O mapa da distribuição geográfica mostrou concentração dos casos nas áreas de classes sociais mais baixas do Município. Conclusão: Houve redução acentuada da incidência de cânceres definidores de Aids, como provável resultado da introdução da HAART. No entanto, crianças e adolescentes com Aids permanecem sob risco aumentado para o desenvolvimento de câncer quando comparadas à população geral. Para aquelas que desenvolveram câncer, o risco para óbito também se mostrou substancialmente elevado / Introduction: The association between human immunodeficiency virus (HIV) infection and cancer has been documented since the beginning of the epidemic of the acquired immunodeficiency syndrome (AIDS). The introduction of the highly active antiretroviral therapy (HAART) has profoundly altered the course of the AIDS epidemic, drastically reducing the incidence of AIDS-defining manifestations, including cancers. Nevertheless, there is limited information on the incidence of cancer in children and adolescents with AIDS living in developing countries. Objective: To describe the cancer epidemiology in children and adolescents with AIDS in the Municipality of São Paulo from 1997 to 2012. Methods: It is a population-based study, using the databases of the Population-based Cancer Registry of São Paulo and the Notifiable Diseases Information System (SINAN). Children and adolescents (< 20 years) with AIDS and cancer have been identified by means of a probabilistic record linkage process between the aforementioned databases. Crude and age-standardized incidence rates per million inhabitants were calculated. To compare the incidence of cancer in people with AIDS and that of the general population, standardized incidence ratio (SIR) and respective 95 per cent confidence intervals (95 per cent CI) were calculated. We examined trends by calculating the annual percent change (APC) and corresponding 95 per cent CI. The analyses of the overall five-year survival after cancer diagnosis among children and adolescents with AIDS and that of the general population were based on the Kaplan-Meier product limit estimator and univariate Cox proportional hazards models. Choropleth maps on monochromatic scales were generated to describe the distribution of cases across the Municipality. Results: We identified 24 cases of cancer in patients with AIDS aged 20 years and younger, of which, 62.5 per cent were AIDS-defining malignancies. The most incident cancers were non-Hodgkin\'s lymphoma, including Burkitt\'s lymphoma (12; 50.0 per cent ), Hodgkin\'s lymphoma (6; 25.0 per cent ) and Kaposi sarcoma (3; 12.5 per cent ). The age-standardized incidence rate was 1,461.3 cases/million. The trend analyses revealed a significant reduction in the incidence of all cancers (APC= -14.5), driven by the decrease in AIDS-defining cancers (APC= -17.0). The overall risk for cancer was significantly increased (SIR= 3.9), especially for non-Hodgkin lymphoma, excluding Burkitts lymphoma (SIR= 22.5), Burkitt\'s lymphoma (SIR= 29.7) and Hodgkin\'s lymphoma (SIR= 18.7). The overall probability of survival at five years after cancer was 56.3 per cent in children and adolescents with AIDS versus 87.5 per cent in the general population. The hazard ratio for death was 5.2 (95 per cent CI= 2.0, 13.6). The map of the geographical distribution showed a concentration of cases in the low-income areas of the Municipality. Conclusion: There was a marked reduction in the incidence of AIDS-defining cancers, likely to be a result of the introduction of HAART. However, children and adolescents with AIDS remain at increased risk for the development of cancer when compared to the general population. For those who developed cancer, the risk of death was also significantly higher

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Background: Despite the effort of scientific research on HIV therapies and to reduce the rate of HIV infection, AIDS remains one of the major causes of death in the world and mostly in sub-Saharan Africa. To date, neither a cure nor an HIV vaccine had been found and the disease can only be managed by using High Active Antiretroviral Therapy (HAART) if detected early. The need for an effective early diagnostic and non-toxic treatment has brought about the necessity for the discovery of additional HIV diagnostic methods and treatment regimens to lower mortality rates. Antimicrobial Peptides (AMPs) are components of the first line of defense of prokaryotes and eukaryotes and have been proven to be promising therapeutic agents against HIV. Methods: With the utility of computational biology, this work proposes the use of profile search methods combined with structural modeling to identify putative AMPs with diagnostic and anti-HIV activity. Firstly, experimentally validated anti-HIV AMPs were retrieved from various publicly available AMP databases, APD, CAMP, Bactibase and UniProtKB and classified according to super-families. Hidden Markov Model (HMMER) and Gap Local Alignment of Motifs (GLAM2) profiles were built for each super-family of anti- HIV AMPs. Putative anti-HIV AMPs were identified after scanning genome sequence databases using the trained models, retrieved AMPs, and ranked based on their E-values. The 3-D structures of the 10 peptides that were ranked highest were predicted using 1-TASSER. These peptides were docked against various HIV proteins using PatchDock and putative AMPs showing the highest affinity and having the correct orientation to the HIV -1 proteins gp120 and p24 were selected for future work to establish their function in HIV therapy and diagnosis. Results: The results of the in silica analysis showed that the constructed models using the HMMER algorithm had better performances compare to that of the models built by the GLAM2 algorithm. Furthermore, the former tool has a better statistical and probability explanation compared to the latter tool. Thus only the HMMER scanning results were considered for further study. Out of 1059 species scanned by the HMMER models, 30 putative anti-HIV AMPs were identified from genome scans with the family-specific profile models after the elimination of duplicate peptides. Docking analysis of putative AMPs against HIV proteins showed that from the 10 best performing anti-HIV AMPs with the highest E-scores, molecules 1,3, 8, and 10 firmly bind the gp120 binding pocket at the VIN2 domain and the point of interaction between gp120 and T cells, with the 1st and 3rd highest scoring anti-HIV AMPs having the highest binding affinities. However, all 10 putative anti-HIV AMPs bind to the N-terminal domain of p24 with large surface interaction, rather than the C-terminal. Conclusion: The in silica approach has made it possible to construct computational models having high performances, and which enabled the identification of putative anti-HIV peptides from genome sequence scans. The in silica validation of these putative peptides through docking studies has shown that some of these AMPs may be involved in HIV/AIDS therapeutics and diagnostics. The molecular validation of these findings will be the way forward for the development of an early diagnostic tool and as a consequence initiate early treatment. This will prevent the invasion of the immune system by blocking the VIN2 domain and thus designing of a successful vaccine with broad neutralizing activity against this domain.

Department of Public health / MPH

MSc (Statistics) / Department of Statistics

PhD (Microbiology) / Department of Microbiology / Introduction Human Immunodeficiency Virus (HIV-1) continues to be a global public health concern, even though Antiretroviral drugs (ARV), especially Highly Active Antiretroviral Therapy (HAART) has significantly reduced morbidity and mortality due to AIDS globally in developed and developing countries. However, there is still a great need to explore every avenue for new therapeutic interventions due to the limitations and side effects of HAART. Potential major breakthroughs for future therapeutic development were the discoveries more than 10 years ago of the role of HIV-1 co-receptors and anti-viral activities of host restriction factors such as APOBEC3G protein, which is a member of the DNA cytosine deaminase family. Entry of HIV in to the host cell is through the attachment of the viral envelope glycoprotein to the CD4 receptor, and subsequent interaction, mainly with either CCR5 or CXCR4 co-receptors. Inhibitors, such as Maraviroc, which binds to CCR5 inhibiting entry of CCR5 utilizing viruses (R5 viruses), is currently reserved for salvage therapy in many countries including South Africa. In the course of HIV infection, CXCR4 utilizing viruses (X4 viruses) may emerge and outgrow R5 viruses, and potentially limit the effectiveness of Maraviroc. Several host cell APOBEC3 genes (A3D, A3F, A3G and A3H) have been shown to restrict HIV, and the HIV viral infectivity factor (Vif) protein serves to antagonize the action of APOBEC3 proteins, promoting viral replication. The CCR5 co-receptor and the HIV Env V3 loop have also been documented as playing roles in HIV-1 disease progression. The interplay between host and viral genes still needs widespread attention, given that disease outcomes of HIV depend on many factors, including host cell genetics. Since the discovery of these genes and their role in HIV replication, many studies have been conducted that show their association with viral polymorphism. The polymorphisms found in host cell genes can have significant effects on viral replication, transmission and fitness and can also contribute to the overall diversity in HIV-1 populations. It is hypothesized that there are significant polymorphisms in HIV-1 and cellular genes that may differ among different populations. Population-based studies have tried to establish a relationship between host factors such as APOBEC3 and CCR5 polymorphism and the rate of disease progression, but most studies have focused on Caucasian populations. In vi contrast, little information is available for the effects of variation in these genes in African populations such as South Africa, where the HIV epidemic has expanded at an alarming rate. Although several population studies have focused on African Americans, these do not give us a complete picture of the potential variation in Africans, though the studies can be a good guide on which to base additional studies. A more comprehensive analysis involving different African populations will likely provide a better understanding of the mechanisms underlying host-pathogen interactions, especially in view of the fact that African Americans are primarily infected with HIV subtype B, which is rarely seen in Africa. Methodology This study characterized the genetic variability of the APOBEC3 D, F, G and H genes as well as the HIV-1 vif, in an ethnically diverse HIV-1 infected South African cohort using Next Generation Sequencing (NGS). In addition, polymorphism in CCR5 was analyzed in conjunction with an analysis of the V3 loop sequences in HIV-1 from this cohort. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) of 192 HIV-1 infected drug-experienced individuals who presented for routine care at the HIV/AIDS Prevention Group Wellness Clinic (HAPG) in Bela-Bela, Donald Fraser Hope Clinic (DFHC) in Vhufhuli and in local clinics in the Vhembe district of Limpopo Province, South Africa. Next generation sequencing custom based (Tn5 tagmentation and amplicon based) protocols to prepare libraries for host and HIV-1 genes were developed and validated with commercially available library preparation kits. The Tn5 tagmentation methods were used for longer DNA fragments and the custom amplicon based methods were used mainly for the shorter DNA fragments. To determine the variability of the APOBEC3 and CCR5 host genes, gene-specific primers were designed to amplify complete 12.16 kb A3D, 13.31 kb A3F, 10.74 kb A3G, 6.8 kb A3H and 1.3 kb CCR5 genes targeting the regions containing the exons. Libraries for the resulting amplicons were prepared using Tn5 transposase tagmentation methods and sequenced on an NGS Illumina MiSeq platforms generating millions of reads with good read coverage for variant calling. Single nucleotide polymorphisms (SNPs) and indels were determined, verified in dbSNPs and compared to SNPs in other populations reported in the 1000 Genome Phase III and HapMap. A Chi-square goodness-of-fit was used to verify if whether observed genotype frequencies were in agreement with the Hardy-Weinberg Equilibrium. Haplotypes and Linkage disequilibrium were inferred to determine SNP association. vii The HIV-1 vif and env V3 loop genes were also sequenced to determine their degree of variability of these genes and to infer co-receptor usage in the South African population. Gene-specific primers were designed to amplify the 579 bp Vif region and 440 bp containing the 105 bp V3 loop. Sequencing libraries from the resulting amplicons were prepared using either the Tn5 transposase or custom-based library preparation methods and sequenced on either an Illumina MiSeq or a MiniSeq platform generating millions of reads with good read coverage for variant calling. Phylogenetic analysis was done to determine the relatedness of the sequences. Major and minor variants were determined for HIV-1 and env V3 loop quasispecies was analysed for co-receptor usage; in an effort to draw inferences for the subsequent utility of Maraviroc as salvage therapy in South Africa. Results and Discussion Next generation library preparation; Tn5 tagmentation based and custom amplicon based protocols to sequence host and HIV genes were successfully developed and used to sequence and characterize variability in host cell APOBEC3D, F, G H, CCR5 and the HIV-1 vif gene and the V3 loop region of the env gene. The HIV-1 env V3 loop sequences generated (and quasispecies analyzed) were used to infer co-receptor usage in treatment-experienced individuals; in an effort to draw inferences for the subsequent utility of Maraviroc as salvage therapy in South Africa. Quality V3 loop sequences were obtained from 72 patients, with 5 years (range: 0-16) median duration on treatment. Subtypes A1, B and C viruses were identified at frequencies of 4% (3/72), 4% (3/72) and 92% (66/72) respectively. Fifty four percent (39/72) of patients were predicted to exclusively harbor R5 viral quasispecies; and 21% (15/72) to exclusively harbor X4 viral quasispecies. Twenty five percent of patients (18/72) were predicted to harbor a dual/mixture of R5X4 quasispecies. Of these 18 patients, about 28% (5/18) were predicted to harbor the R5+X4, a mixture with a majority R5 and minority X4 viruses, while about 72% (13/18) were predicted to harbor the R5X4+ a mixture with a majority X4 and minority R5 viruses. The proportion of all patients who harboured X4 viruses either exclusively or dual/mixture was 46% (33/72). Thirty-five percent (23/66) of the patients who were of HIV-1 subtype C were predicted to harbor X4 viruses (χ2=3.58; p=0.058), and 57% of these (13/23) were predicted to harbor X4 viruses exclusively. CD4+ cell count less than 350 cell/μl was associated with the presence of X4 viruses (χ2=4.99; p=0.008). The effectiveness of Maraviroc as a component in salvage therapy may be compromised for a significant number of chronically infected patients harboring CXCR4 utilizing viii viruses in the study cohort. Although from the current study a subset of patients harboring CCR5 utilizing viruses may benefit from Maraviroc, characterizing and identifying if variation in CCR5 are located at Maraviroc binding sites was of importance to investigate. The following variants; P35P, S75S, Y89Y, A335V and Y339F and their varying frequencies were detected in the CCR5 gene. The A335V variant was detected at a higher frequency of 17.4% (29/167). The G265S variant is reported for the first time in this study at 0.6% (1/167) frequency. The SNPs detected were in strong LD (D’= 1, R2 = 0.0) with minor deviation from the Hardy-Weinberg Equilibrium. These variants were not located at the binding motif of Maraviroc. The variants A335V and Y339F were detected at a higher frequency in this study than previously reported in South Africa. Variability in APOBEC3 host cell genes was also characterized in our study cohort. The following APOBEC3 variants compared to the GRCh37 consensus sequence were detected: R97C, R248K and T316T in A3D; R48P, A78V, A108S, S118S, R143R, I87L, Q87L, V231I, E245E, S229S, Y307C and S327S in A3F; S60S, H186R, R256H, Q275E and G363R in A3G and N15Δ, G105R, K140E, K121D, E178D in A3H. Minor allele frequency variants (MAF<5%); L221L, T238I, C224Y and C320Y in A3D; I87L, P97L and S229S in A3F; R256H, A109A, F119F and L371L in A3G, which are frequent in the European population, were also detected. In addition, novel R6K, L221R and T238I variants in A3D and I117I in A3F were detected. Most of the SNPs were in strong LD with minor deviation from the Hardy-Weinberg Equilibrium. Four, six, four, and three haplotypes were identified for A3D, A3F, A3G, and A3H respectively. In general, polymorphism in A3D, 3F, 3G and 3H were higher in our South African cohort than previously reported among other African, European and Asian populations. The APOBEC3 antagonist HIV-1 vif gene was also sequenced to determine the level of diversity in a South African population and also correlated with APOBEC3 variation. Functional Vif without frameshift mutation was observed in all samples except in 4 samples. The functional domain and motifs, such as Zn binding motifs, proline-rich domain, human casein kinase, and the N and C-terminal CBF interaction site were highly conserved. APOBEC binding motifs and the nuclear localization signal were less conserved in the South African HIV-1 Vif. APOBEC3 H variation strongly correlates with Vif variation. All the Vif sequences were subtype C, except one sample, which was identified as an A1/C recombinant. The vif gene in a South African population was under purifying selection, with the dS= 0.2581 and dN= 0.0684 and the dN/dS value = 0.265. There is a high genetic diversity in the South African vif gene, which may ix influence the neutralization and restriction of APOBEC genes. Conclusions In conclusion, the protocols developed in this study can be applied to amplify and sequence any host and HIV-1 genes of interest allowing much deeper and more sensitive profiling of host gene and HIV-1 genetic diversity. Our findings show that a highly significant number of chronically HIV-1 subtype C infected patients in Maraviroc-free treatment harbor CXCR4 utilizing viruses. The data is useful in the consideration of whether to include entry antagonists such as Maraviroc in alternative forms of treatment for patients failing second line treatment regimen in the study setting. The determination of co-receptor usage prior to initiation of therapy consisting of Maraviroc is suggested. Variation in the CCR5 coding region were observed at higher frequencies compare to other studies conducted in South African populations at different locations. This data may suggest that different populations in South Africa have different SNP frequencies. All the polymorphisms identified in the study were not located at the Maraviroc binding motif, therefore the subset of patient infected by R5 viruses may benefit from this drug. We have shown that significant APOBEC3 variation exists among an ethnically diverse population of South Africa by providing extensive data for 4 different A3 genes that are known to restrict HIV infection, but have only been sparsely studied in African populations. This study provides a baseline for future studies that would functionally characterize SNPs identified in this population, in order to understand the role of novel and/or low frequency variants observed. Ex vivo and in vivo studies will increase our understanding of how these variants might have cumulatively impacted the epidemic in Northern South Africa. This study also shows that there is a high level of HIV-1 Vif diversity in the study area. This diversity may impact the expression and packaging of Vif proteins, and the infectivity of HIV. In addition, a significant correlation was observed between HIV-1 Vif variation and APOBEC3 H haplotypes. / NRF

Объектом исследования является система оказания психологической и социальной помощи ВИЧ-инфицированным пациентам. Предмет исследования: роль и участие специалистов учреждений социального обслуживания населения в системе профилактики и оказания медицинской помощи больным ВИЧ-инфекцией. Целью магистерской диссертации является выявление роли специалистов «немедицинского сервиса» по профилактике и преодолению ВИЧ-инфекции, как социально-значимого заболевания в рамках межведомственного взаимодействия (на примере Свердловской области). Выпускная квалификационная работа посвящена изучению роли специалистов «немедицинского сервиса» в профилактике и преодолении социально-значимого заболевания в рамках межведомственного взаимодействия (на примере Свердловской области). В работе рассмотрены теоретические основы межведомственного взаимодействия как социальной технологии, в процессе профилактики ВИЧ-инфекции; с использованием авторской анкеты выявлены основные возможности и затруднения специалистов учреждений социального обслуживания населения в оказании помощи здравоохранению по преодолению распространения ВИЧ-инфекции, а так же выявлены основные потребности ЛЖВ (людей, живущих с ВИЧ); проведён контент-анализ существующей и разработано авторское дополнение к основной образовательной программе ГАУЗ СО ОЦ СПИД по подготовке специалистов «немедицинского сервиса» к мотивационному консультированию, которая при апробации показала положительные результаты в части удовлетворения потребностей и пациентов ВИЧ+, и учреждений здравоохранения. Работа будет интересна студентам и специалистам в области социальной работы с ЛЖВ. / The final qualifying work is devoted to the study of the role of specialists of the "non-medical service" in the prevention and overcoming of socially significant diseases within the framework of interdepartmental interaction (on the example of the Sverdlovsk region). The paper considers the theoretical foundations of interdepartmental interaction as a social technology in the process of HIV infection prevention; using the author's questionnaire, the main opportunities and difficulties of specialists from social service institutions in providing health care to overcome the spread of HIV infection are identified, as well as the basic needs of PLHIV (people living with HIV) are identified; an author's supplement is developed to the main educational program of the State Medical Institution of the Russian Academy of Sciences on the preparation of specialists of the "non-medical service" for motivational training, which, when tested, showed positive results in meeting the needs of both HIV+ patients and healthcare institutions. The work will be of interest to students and specialists in the field of social work with PLHIV.