Thesis (MPH.) -- University of Limpopo, 2022 / Human Immunodeficiency Virus (HIV) has affected all parts of the world, and as of 2019, more than 76 million people have been infected by HIV. South Africa has the largest population of people living with human immunodeficiency virus (HIV) in the world and the highest infected group were aged 24 to 49, and females had the highest percentage in viral load suppression for all age groups. HIV infection leads to advanced loss of CD4 T cells and the roll out of antiretroviral therapy (ART) has bring about in significant cutbacks in HIV-associated complications by recovering the CD4+ T cell count. Some patients may not be successful in attaining this result, and some may accomplish it only after a number years of treatment. The disease progression and the health conditions amongst People Living with HIV-AIDS (PLWA) has improved substantially in the past two decades. The purpose of this study was to evaluate the disease progression of the patients initiated on ART from 2017 to 2019 at the University of Limpopo Health Centre, in Limpopo province. Methodology: A descriptive retrospective investigation was carried out which followed a quantitative approach in which secondary data from medical files of 259 patients initiated on ART at University of Limpopo Health Centre was used. where outcomes of ART initiation assessed and evaluated in association with characteristics of patients. Data analysis was done using the STATA statistical software version 12 for Windows (STATA Corporation, College Station, Texas). Frequency tables were used to make comparisons between groups for continuous and categorical variables using student t-test, and chi-square test. P-value less than 0.05 at 95% confidence level were regarded as significant. Results: The research finding revealed 80.0% of the study participants were females and the mean age group of participants diagnosed HIV positive was 28.28 years with standard deviation of ±7.5. The mean of the CD4 count cells at baseline for females was 411.4 cells/μL while for males was 341.2 cells/μL (p=0.212). The mean CD4 count cells at last ART visit for females was 613.7 cells/μL while for males was 452.9 cells/μL (p<0.001). There has been significant increase of the CD4 cell count from the baseline to the last ART visit as it is noted in the increase in proportion of patients with CD4 cell count of more than 500 in all the years. The proportion of patients with baseline CD4 cell count of 200 to 350 (moderate immunodepression) were high in 2019 and 2017 at 40.6% and 40.3% respectively. Majority of the patients were transferred out to other facilities at 79.4% as most patients are students and only 2.3% mortality rate has been reported for the study period. Majority of the patients initiated on ART at University of Limpopo were in WHO stage 2 at 45.5% followed by those in stage 3 and stage 1 at 22.2% and 21.8% respectively. Patients who were 24 years or older were 1.1 times more likely to have improved CD4 cell count at the last date of ART visit as compared to younger patients but not statistically significant while males were 3.5 times more likely to have improved CD4 cell count at the last date of ART visit as compared to females which was statistically significant. Patients who were initiated on ART at WHO stage 4 were 6.67 more likely to have improved CD4 cell count at the last date of ART visit as compared to those who were initiated on ART at WHO stage 1. Conclusion: The treatment progression in the study setting was found to be convincing and acceptable which is similar to the findings reported in other studies in many other countries. The significance of CD4 cell counts monitoring for HIV patients cannot be overemphasised. This study recommends a strengthened testing and treatment programme targeted males amongst the university community, enhance provider provider relationship when patients are transferred out to other health facilities, enhance the collection of baseline and progressive data on both the CD4 cell count and viral load.

HIV/AIDS is raging and causing millions of deaths around the world. The major challenge in treating HIV/AIDS is the establishment of HIV reservoirs where the viruse escapes both drug and immune system attempts at eradication. Throughout the course of HIV/AIDS, productive HIV infection occurs primarily in the lymphoid follicles or germinal centers (GC) surrounding follicular dendritic cells (FDC). In the GCs, FDCs trap and maintain infectious HIV for years and provide these infectious viruses to the host cells. FDCs also attract B and T cells into the GCs and increase the ability of CD4+ T cells to be infected. Additionally, FDCs also mediate the increase of HIV replication in HIV-infected CD4+ T cells. Recently, several clinical cases and in vitro studies suggest that alpha-1-antitrypsin (AAT) might inhibit HIV infection and replication. Therefore, I hypothesized that AAT inhibited both the infection and replication of HIV in primary CD4+ T cells. I also postulated that AAT inhibited the FDC-mediated contributions that potentiate HIV infection and replication. To test whether AAT inhibited HIV infection in lymphocytes, CD4+ T cells were pretreated with AAT and then incubated with HIV to detect HIV infection. To exam whether AAT inhibited HIV replication, infected CD4+ T cells were cultured with AAT to detect the replication of HIV. To determine whether AAT blocked the FDC-mediated contributions to HIV pathogenesis, activated or resting FDCs were treated with AAT to detect the trapping and maintenance of HIV. The results suggested that AAT inhibited HIV entry into CD4+ T cells by directly interacting with gp41 and thereby inhibiting the interaction between HIV and CD4+ T cells. AAT also inhibited HIV replication in infected CD4+ T cells. Further study revealed that AAT interacted with low-density lipoprotein-receptor related protein to mediate the internalization of AAT through a clathrin-dependent endocytic process in CD4+ T cells. Subsequently, internalized AAT was transported from the endosome to the lysosome and then released into the cytosol. In the cytosol, AAT directly interacted with IκBα to block its polyubiquitinylation at lysine residue 48, which resulted in the accumulation of phosphorylated/ubiqutinylated IκBα in the cytosol. In turn, the dissociation of IκBα from NF-κB was blocked, which thereby inhibited the nuclear translocation and activation of NF-κB. Additionally, AAT also down-regulated FDC-CD32 and FDC-CD21 expression, which are regulated by NF-kB, thereby inhibiting the trapping and maintenance of HIV on FDCs. Hence, AAT not only suppresses HIV replication, but also blocks HIV replication in CD4+ T cells. Moreover, AAT also inhibits the activation of FDCs thereby affecting the trapping and maintenance of HIV.

Master dissertation consists of theoretical and empirical parts. Theoretical part observes medical and psychological issues of HIV infection, development scheme of cognitive function in teenage, development points of cognitive functions of children and teenagers with positive HIV status. Empirical part observes comparative results of HIV positive and negative status teenager’s cognitive functions research. The research showed that HIV-positive teenagers' cognitive functions are developed worse, than healthy. / Магистерская диссертация содержит теоретическую и эмпирическую часть. В теоретической части представлен обзор медико-психологических особенностей ВИЧ-инфекции, закономерностей развития когнитивных функций в подростковом возрасте, особенностей развития когнитивных функций у ВИЧ-инфицированных детей и подростков. В эмпирической части описываются сравнительные результаты исследования когнитивных функций у подростков с положительным и отрицательным ВИЧ-статусом. Исследование показало, что у ВИЧ-инфицированных подростков когнитивные функции развиты хуже, чем у здоровых.

La thérapie antirétrovirale (TAR) réduit drastiquement la transmission verticale du VIH. Cependant, des études récentes démontrent une association entre l'utilisation de la TAR pendant la grossesse, particulièrement à base d’inhibiteurs de protéases (IP), et les issues adverses, notamment l’accouchement prématuré. Les objectifs principaux de mon mémoire étaient de caractériser le profil immunitaire/inflammatoire au niveau placentaire et systémique chez les personnes enceintes vivant avec le VIH (PEVVIH) et les comparer en fonction du statut VIH et de la classe de TAR. Au niveau placentaire, l'immunotypage des cellules Hofbauer a révélé que les placentas des PEVVIH contenaient un niveau significativement plus élevé de leucocytes CD45+ attribuable à une augmentation du nombre de cellules Hofbauer que le groupe contrôle. Les analyses multivariables ont révélé que cette augmentation des cellules immunitaires était associée à un profil prédominant CD163+ dans tous les sous-groupes de TAR par rapport au groupe de contrôle. Au niveau systémique, la quantification de 12 médiateurs inflammatoires dans le plasma périphérique a révélé que la TAR à base d'IP est associée à une libération de cytokines pro-inflammatoires et antivirales significativement plus élevée par rapport à la TAR à base d'InSTI aux deux trimestres étudiés, en plus d’être associée à l’accouchement prématuré et une charge virale plus élevée au deuxième trimestre. Ces résultats suggèrent que la classe de TAR n'affecte pas intrinsèquement la sélection des cellules Hofbauer CD163+ et CD68+ au niveau placentaire, mais que la TAR à base d'IP est associée à une réponse immunologique distincte qui augmente le risque d'accouchement prématuré. / Antiretroviral therapy (ART) drastically reduces vertical transmission of HIV. However, recent studies demonstrate an association between the use of ART during pregnancy, particularly protease inhibitor (PI)-based ART, and adverse outcomes, including preterm delivery. The main objectives of my dissertation were to characterize the inflammatory profile at the placental and systemic levels in pregnant people living with HIV (PPLWH) and compare them according to HIV status and ART class. At the placental level, Hofbauer cell immunotyping revealed that placentas of PPLWH contained a significantly higher number of CD45+ leukocytes due to an increase in Hofbauer cells compared to controls. Multivariate analyses revealed that this increase in immune cells was associated with a predominantly CD163+ profile in all ART subgroups compared with the control group. At the systemic level, the quantification of 12 inflammatory mediators in peripheral plasma revealed that PI-based ART was associated with significantly higher pro-inflammatory and antiviral cytokine release compared to InSTI-based ART in both trimesters studied, in addition to being associated with preterm delivery and higher viral load. These results suggest that the class of ART does not intrinsically affect the selection of CD163+ and CD68+ Hofbauer cells in the placenta, but that PI-based ART is associated with a distinct immunological response which may increase the risk of preterm delivery.

Motivation Alcohol consumption is one of the major risk factors of cardiovascular disease (CVD). Excessive alcohol drinking is the fifth leading cause of death worldwide and the prevalence of alcohol abuse continues to increase especially in low-income areas of sub-Saharan Africa. The alarming rate of urbanisation seems to be the driving force for excessive alcohol intake in the developing world. In addition to its influence on CVD, heavy drinking also results in a number of non-cardiovascular consequences that include injury, risky sexual behaviour, violent crime and family dysfunction among black South Africans, contributing to high mortality. Moreover, the highest number of individuals with human immunodeficiency virus (HIV) infection in South Africa is partly attributable to high intake of alcohol. HIV remains a major concern in South Africa with significant funding diverted to address the pandemic. The continued increases in mortality from preventable outcomes such as stroke, myocardial infarction and renal failure are largely due to urbanisation, poverty and dysfunctional health systems working with limited budgets. These are some of the factors requiring in-depth study of the scientific aspects of alcohol intake in South Africa. Although there is enough evidence that links excessive drinking with hypertension and CVD, the markers of alcohol intake – self reporting of alcohol, gamma-glutamyltransferase (GGT) and carbohydrate deficient transferrin – are still not specific enough to isolate other confounding factors in the association of alcohol intake with CVD. The markers of alcohol that independently predict CVD and mortality need to be explored. Finally, the severe lack of longitudinal investigations on alcohol-related hypertension development and total mortality in black South Africans has compromised the early identification of risk factors associated with these outcomes. This study will therefore attempt to address the limited availability of longitudinal studies and stimulate interest for continued investigation. Aim The aim of this study was to investigate whether alcohol intake of black South Africans is related to specific measures of cardiovascular function (change in blood pressure (BP), hypertension development) and mortality over a period of 5 years. Methodology This study was based on the international Prospective Urban and Rural Epidemiology (PURE) study which includes 26 countries, investigating the cause and development of cardiovascular risk factors in low, middle and high income countries. This South African leg of the PURE study started in 2005 in which the baseline data was collected from 2021 black South Africans from rural and urban areas in Ikageng, Ganyesa and Tlakgameng in the North West Province. Eleven participants presented with missing data, leaving 2010 participants with complete datasets at baseline. However, data from these 11 participants was useful, especially for Chapter 4. All participants gave informed consent and the Ethics committee of the North-West University (Potchefstroom Campus) approved the study. The follow-up data collection was done in 2010. General health questionnaires, anthropometric measurements, lipid profiles and cardiovascular measurements were taken both at baseline and follow-up using appropriate methods. We also collected blood samples and performed biochemical analyses for lipid markers, liver enzymes, inflammatory markers and percentage carbohydrate deficient transferrin (%CDT). Finally, we obtained data on cardiovascular and non-cardiovascular mortality through verbal autopsy and death certificates. We made use of analysis of variance (ANOVA) and Chi-square tests to compare means and proportions, respectively. We used dependent t-tests and the McNemar test to compare baseline and follow-up variables. Furthermore, we employed single and partial linear regression analyses to correlate alcohol markers with each other and with the cardiovascular measures. Multiple regression analyses were used to correlate dependent variables in the study with various independent variables as required. Finally, we employed multivariable-adjusted Cox regression analyses to assess the association of the selected alcohol markers with mortality while adjusting for several independent variables. Results and Conclusions of each manuscript - With the first research article (Chapter 4), we aimed to compare self-reported alcohol intake estimates with GGT and %CDT, considering their relationship with percentage change in brachial blood pressure (BP) and central systolic blood pressure (cSBP) over 5 years. The results indicated that only self-reported alcohol intake independently predicted % change in brachial BP and cSBP. This was not found for the biochemical markers GGT and %CDT. Self-reported alcohol intake seems to be an important measure to implement by health systems in low income areas of sub-Saharan Africa, where honest reporting is expected. - Given the likely presence of high GGT levels in both alcohol consumption and non-alcoholic fatty liver disease (NAFLD), the second manuscript (Chapter 5) aimed to compare the cardiovascular and metabolic characteristics of excessive alcohol users and individuals with suspected NAFLD (confirmed with self-report, GGT and %CDT). We found that different sex and cardiometabolic profiles characterised excessive alcohol users and individuals suspected with NAFLD. Lean body mass and male sex were the dominant characteristics in excessive alcohol use while the NAFLD group had a dysmetabolic profile with obese women making up the higher proportion of this group. In excessive alcohol users systolic blood pressure and pulse pressure were independently associated with high-density lipoprotein cholesterol. Diastolic blood pressure showed a significant correlation with waist circumference. These disparate profiles may guide healthcare practitioners in primary healthcare clinics to identify individuals with elevated GGT levels who may suffer from NAFLD or alcohol overuse. These results emphasise the importance of modifiable risk factors as the main contributors to CVD and that lifestyle change should be the main focus in developing countries such as South Africa. - The third manuscript (Chapter 6) aimed to determine the measure of alcohol intake (selfreported alcohol intake, GGT and %CDT) that related best with hypertension development, cardiovascular and all-cause mortality over 5 years in the same population of black South Africans. We found that GGT was the only independent predictor of hypertension development, cardiovascular as well as all-cause mortality. Moreover, self-reporting of alcohol intake predicted incident hypertension, confirming our findings from Chapter 4. The third marker, %CDT, a highly specific marker of alcohol intake, was not related with any outcome variable, perhaps due to its low sensitivity. Although self-reported alcohol intake is useful in low-resource primary healthcare settings, measurement of GGT is encouraged due to its predictive value for hypertension and mortality. GGT represents alcohol intake, non-alcoholic steatohepatitis and obesity - all known to have severe cardiovascular consequences. Discussion and Conclusions Excessive alcohol intake remains a major concern in the development of hypertension, CVD and premature death in sub-Saharan Africa. Despite their weaknesses such as bias and nonspecificity, self-reporting of alcohol consumption and GGT emerged as reliable alcohol markers that independently predicted 5-year change in BP, hypertension development and total mortality in this population. Serum %CDT did not show any association with the mentioned cardiovascular markers. Finally, we were also able to show that black South Africans with suspected NAFLD (i.e. with high GGT levels who do not consume alcohol) are typically obese women, whereas lean men were more likely to have high alcohol consumption. Further prospective investigations are encouraged regarding (a) these mentioned associations, as well as (b) other self-reporting estimates such as quantity and frequency of drinking and (c) the use of %CDT as a highly specific marker of alcohol intake. The simultaneous presence of HIV infection in alcohol abuse in this population also warrants further investigation. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Motivation Alcohol consumption is one of the major risk factors of cardiovascular disease (CVD). Excessive alcohol drinking is the fifth leading cause of death worldwide and the prevalence of alcohol abuse continues to increase especially in low-income areas of sub-Saharan Africa. The alarming rate of urbanisation seems to be the driving force for excessive alcohol intake in the developing world. In addition to its influence on CVD, heavy drinking also results in a number of non-cardiovascular consequences that include injury, risky sexual behaviour, violent crime and family dysfunction among black South Africans, contributing to high mortality. Moreover, the highest number of individuals with human immunodeficiency virus (HIV) infection in South Africa is partly attributable to high intake of alcohol. HIV remains a major concern in South Africa with significant funding diverted to address the pandemic. The continued increases in mortality from preventable outcomes such as stroke, myocardial infarction and renal failure are largely due to urbanisation, poverty and dysfunctional health systems working with limited budgets. These are some of the factors requiring in-depth study of the scientific aspects of alcohol intake in South Africa. Although there is enough evidence that links excessive drinking with hypertension and CVD, the markers of alcohol intake – self reporting of alcohol, gamma-glutamyltransferase (GGT) and carbohydrate deficient transferrin – are still not specific enough to isolate other confounding factors in the association of alcohol intake with CVD. The markers of alcohol that independently predict CVD and mortality need to be explored. Finally, the severe lack of longitudinal investigations on alcohol-related hypertension development and total mortality in black South Africans has compromised the early identification of risk factors associated with these outcomes. This study will therefore attempt to address the limited availability of longitudinal studies and stimulate interest for continued investigation. Aim The aim of this study was to investigate whether alcohol intake of black South Africans is related to specific measures of cardiovascular function (change in blood pressure (BP), hypertension development) and mortality over a period of 5 years. Methodology This study was based on the international Prospective Urban and Rural Epidemiology (PURE) study which includes 26 countries, investigating the cause and development of cardiovascular risk factors in low, middle and high income countries. This South African leg of the PURE study started in 2005 in which the baseline data was collected from 2021 black South Africans from rural and urban areas in Ikageng, Ganyesa and Tlakgameng in the North West Province. Eleven participants presented with missing data, leaving 2010 participants with complete datasets at baseline. However, data from these 11 participants was useful, especially for Chapter 4. All participants gave informed consent and the Ethics committee of the North-West University (Potchefstroom Campus) approved the study. The follow-up data collection was done in 2010. General health questionnaires, anthropometric measurements, lipid profiles and cardiovascular measurements were taken both at baseline and follow-up using appropriate methods. We also collected blood samples and performed biochemical analyses for lipid markers, liver enzymes, inflammatory markers and percentage carbohydrate deficient transferrin (%CDT). Finally, we obtained data on cardiovascular and non-cardiovascular mortality through verbal autopsy and death certificates. We made use of analysis of variance (ANOVA) and Chi-square tests to compare means and proportions, respectively. We used dependent t-tests and the McNemar test to compare baseline and follow-up variables. Furthermore, we employed single and partial linear regression analyses to correlate alcohol markers with each other and with the cardiovascular measures. Multiple regression analyses were used to correlate dependent variables in the study with various independent variables as required. Finally, we employed multivariable-adjusted Cox regression analyses to assess the association of the selected alcohol markers with mortality while adjusting for several independent variables. Results and Conclusions of each manuscript - With the first research article (Chapter 4), we aimed to compare self-reported alcohol intake estimates with GGT and %CDT, considering their relationship with percentage change in brachial blood pressure (BP) and central systolic blood pressure (cSBP) over 5 years. The results indicated that only self-reported alcohol intake independently predicted % change in brachial BP and cSBP. This was not found for the biochemical markers GGT and %CDT. Self-reported alcohol intake seems to be an important measure to implement by health systems in low income areas of sub-Saharan Africa, where honest reporting is expected. - Given the likely presence of high GGT levels in both alcohol consumption and non-alcoholic fatty liver disease (NAFLD), the second manuscript (Chapter 5) aimed to compare the cardiovascular and metabolic characteristics of excessive alcohol users and individuals with suspected NAFLD (confirmed with self-report, GGT and %CDT). We found that different sex and cardiometabolic profiles characterised excessive alcohol users and individuals suspected with NAFLD. Lean body mass and male sex were the dominant characteristics in excessive alcohol use while the NAFLD group had a dysmetabolic profile with obese women making up the higher proportion of this group. In excessive alcohol users systolic blood pressure and pulse pressure were independently associated with high-density lipoprotein cholesterol. Diastolic blood pressure showed a significant correlation with waist circumference. These disparate profiles may guide healthcare practitioners in primary healthcare clinics to identify individuals with elevated GGT levels who may suffer from NAFLD or alcohol overuse. These results emphasise the importance of modifiable risk factors as the main contributors to CVD and that lifestyle change should be the main focus in developing countries such as South Africa. - The third manuscript (Chapter 6) aimed to determine the measure of alcohol intake (selfreported alcohol intake, GGT and %CDT) that related best with hypertension development, cardiovascular and all-cause mortality over 5 years in the same population of black South Africans. We found that GGT was the only independent predictor of hypertension development, cardiovascular as well as all-cause mortality. Moreover, self-reporting of alcohol intake predicted incident hypertension, confirming our findings from Chapter 4. The third marker, %CDT, a highly specific marker of alcohol intake, was not related with any outcome variable, perhaps due to its low sensitivity. Although self-reported alcohol intake is useful in low-resource primary healthcare settings, measurement of GGT is encouraged due to its predictive value for hypertension and mortality. GGT represents alcohol intake, non-alcoholic steatohepatitis and obesity - all known to have severe cardiovascular consequences. Discussion and Conclusions Excessive alcohol intake remains a major concern in the development of hypertension, CVD and premature death in sub-Saharan Africa. Despite their weaknesses such as bias and nonspecificity, self-reporting of alcohol consumption and GGT emerged as reliable alcohol markers that independently predicted 5-year change in BP, hypertension development and total mortality in this population. Serum %CDT did not show any association with the mentioned cardiovascular markers. Finally, we were also able to show that black South Africans with suspected NAFLD (i.e. with high GGT levels who do not consume alcohol) are typically obese women, whereas lean men were more likely to have high alcohol consumption. Further prospective investigations are encouraged regarding (a) these mentioned associations, as well as (b) other self-reporting estimates such as quantity and frequency of drinking and (c) the use of %CDT as a highly specific marker of alcohol intake. The simultaneous presence of HIV infection in alcohol abuse in this population also warrants further investigation. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

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)

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)

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