MSc (Med), Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand / Background. South Africa is currently experiencing one of the most severe AIDS epidemics in the world. The major challenge lies in prompt identification and early initiation of treatment in those eligible for HAART. Clinical staging has previously been recommended for use in settings where CD4 + count testing is not available. We conducted secondary data analysis to determine whether clinical symptoms and signs are useful in predicting the need for HAART initiation (CD4 + count < 200 cells/μL) in South Africa. Methods. Screening data from a randomized controlled trial in women who were HIV positive were analysed. All participants were interviewed using a structured questionnaire to elicit symptom history and then physical examination was done. Participants were staged using WHO criteria. Blood was drawn for CD4 + testing. The association between signs and symptoms and a CD4 + < 200 cells/μL was assessed using logistic regression. Results. Among 589 HIV infected women aged between 18 and 58 years, 90% were assessed as WHO clinical stages I/II. The median CD4 + count was 403 cells/μL (IQR: 273-586). Among women who were WHO stage I/II, 13% had CD4 + count < 200 cells/μL and required HAART. The WHO clinical staging had a low sensitivity (4%) but high specificity for detecting those that require treatment. Conclusion: In a setting where asymptomatic patients are diagnosed with HIV, clinical assessment can not replace CD4 + count testing as a method of identifying those that need treatment.

MSc (Med), Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand / Background: Few studies have compared the sociodemographic characteristics and treatment outcomes of HIV/AIDS patients in rural and urban South Africa. Aim: This study compared the baseline socio-demographic characteristics and treatment outcomes (time to mortality, immunologic and virologic response) of HAART-naïve patients in urban and rural South Africa. Methodology: A secondary analysis of data obtained from the Themba Lethu Clinic, Helen Joseph Hospital, Johannesburg (urban site) and the ACTS clinic, Mpumalanga (rural site) from January 2005 to December 2008 was used to make comparison of baseline socio-demographic and clinical characteristics of patients in both cohorts. The survival experience and predictors of mortality was performed using Kaplan – Meier survival analysis and Cox proportional hazards models while effects on immunologic and virologic responses to HAART were modeled using logistic regression. Results: At initiation of HAART, the rural cohort had similar CD4 count and body mass index, but lower haemoglobin levels, compared to the urban cohort. The median follow up time for both cohorts was 566 days with the urban cohort having a mortality rate of 5.6/100 person-years compared to the 4.8/100 person-years of the rural cohort. CD4 count, BMI and WHO stage were predictors of mortality in both cohorts. Logistic regression models for virologic and immunologic response did not show any difference by site in the multivariate models. Conclusion: Though there are differences in the baseline sociodemographic and clinical characteristics of rural and urban patients starting HAART for the first time, achievement of immunologic and virologic response at 6 months of therapy were similar in both cohorts. Continued public health enlightenment campaigns and nutritional support programs should be undertaken to ensure patients present early and benefit from treatment.

MSc (Med), Bioethics and Health Law, Faculty of Health Sciences, University of the Witwatersrand / South Africa, like many other developing nations, is faced with the challenge of mobilising resources to fight the HIV/AIDS pandemic. There is a huge budget gap between the ideal and actual funding provided to achieve universal access to highly active antiretroviral therapy (HAART), which leads to the inevitable rationing of HAART. Although healthcare spending has been increasing in South Africa, new demands are being placed on the HAART roll out programmes. This is particularly due to the emergence of HIV drug resistance (HIVDR). Because non-adherence to HAART is strongly linked to drug resistance, this is a major threat to any successful HAART programme. In the face of restricted resources, this research report looks at some of the ethical and economic implications of non-adherence to HAART. I suggest that there is merit in considering that HAART be restricted only to adherent patients.

Highly antiretroviral therapies (HAART) have been implemented to slow the progression of the human immunodeficiency virus (HIV). Although these new advances in the medications for HIV-positive patients have contributed in longer life expectancy, comorbidities, such as cardiovascular disease, still cause higher number of deaths among HIV-positive patients than in the regular population. Because of the intrinsic inflammation caused by the HIV virus, atherogenesis is more likely to occur and is driven by infected macrophages. These macrophages are known to secrete cathepsins, but infection causes the macrophages not to perform their function properly as an immune agent. I hypothesize that antiretroviral drugs play an important role in arterial remodeling by affecting cells within the artery and causing an alteration of cathepsin activity, leading to an increased risk of atherosclerosis in HIV patients. To test this hypothesis, we incubated THP-1 monocytes with antiretroviral drugs efavirenz and tenofovir individually to observe any changes in cathepsin activity. These lysates were analyzed through multiplex cathepsin zymography and quantified through densitometry. We found that our hypothesis held true for efavirenz and tenofovir in THP-1 monocytes, which caused decreased cathepsin K activity compared to vehicle controls. Still, stimulation of peripheral blood mononuclear cells (PBMCs) with efavirenz and tenofovir caused differential effects. Together, our data suggest that the HAART interaction with monocytes that are physiologically relevant to our system possibly contributes to the advancement of atherogenesis in HIV+ patients.

Desde el inicio de la epidemia de SIDA, hacia 1980, se estima que en todo el mundo se han producido más de 16 millones de muertes. En la actualidad se calcula que viven unos 33 millones de personas infectadas por el VIH, mas del 90% de ellas en países del Tercer Mundo. España, con más de 50.000 casos de sida declarados, es uno de los países europeos con mayor tasa de incidencia. La profilaxis de determinadas infecciones oportunistas y el adecuado diagnóstico y tratamiento de las enfermedades asociadas, permiten mejorar la calidad de vida y la supervivencia de los sujetos infectados. Pero ha sido la introducción de los medicamentos antirretrovirales (ingeridos en forma de combinaciones o "cócteles") lo que ha permitido la mejora sustancial del pronóstico de infección por VIH en los últimos años. Debido a distintos factores (como los efectos secundarios o la interacción entre los diversos componentes del "cóctel") los tratamientos antirretrovirales de gran actividad que se recomiendan en la actualidad son difíciles de tomar correctamente para los pacientes. El objetivo de la presente tesis es justamente examinar dichas dificultades, especialmente lo relacionado con la adherencia y la respuesta clínica a las modalidades de tratamiento antirretroviral que se utilizan en la actualidad.

Nuestro objetivo ha sido determinar el impacto del tratamiento antirretroviral de gran actividad (HAART) en el grupo de pacientes infectados por el virus de inmunodeficiencia adquirida (VIH) ingresados en el Hospital Clínic desde 1984 hasta el año 2000. Para ello, hemos preparado un estudio retrospectivo en el que los pacientes se han estratificado atendiendo a tres períodos diferentes, según el tipo de terapia disponible en cada caso: sin terapia (1984-1987), sin HAART (1988-1996)y con HAART (1997-2000). Hemos comparado la incidencia de infecciones oportunistas, de las neoplasias y la mortalidad en dichos periodos mediante el modelo de Poisson de estimación del "Incidence Rate Ratio" (IRR).

Objective To determine the reasons for the change or modification in the first line HAART regimen (1a and 1b) in HIV positive patients at the Thusong CCMT site. Methods This study is a quantitative descriptive study using a standardized data collection tool to extract retrospective data from medical records. Subjects Subjects for this study included patients 18 years or older attending the Thusong CCMT site, which were started on HAART regimens 1a or 1b and were on treatment for at least 6 months. The final sample size evaluated was 257 patients. Results There was a high rate (43%) of change or modification of the first line HAART regimen. Majority of the patient’s (72%) had their regimen modified due to side effects of the drugs and only a small number (9.7%) of patients had a complete change in the regimen due to virological failure. Stavudine (d4T) associated lipodystrophy was the most common side effect (45.5%) followed by peripheral neuropathy (16.7%), leading to treatment modification. Conclusion The rate of modification or change of first line HAART regimen, at Thusong CCMT, was fairly high (42.6%), and the most common reason for the modification or change was drug side effect of stavudine (d4T).

Magister Scientiae Dentium - MSc(Dent) / Introduction: Xerostomia and reduced salivary flow have been reported often enough among HIV positive patients. Strong associations have also been established between HIV infection and oral effects of reduced salivary flow like xerostomia, high DMFT, increased candidial infection etc. Besides the direct effect of HIV infection, xerostomia and reduced salivary flow have also been reported as a side effect of Highly Active Anti Retroviral reatment (HAART). Studies have shown that xerostomia has a negative effect on the quality of life of people living with HIV & AIDS. Although reduced salivary flow is a main cause for xerostomia, complaints of xerostomia is also found in the absence of salivary flow deficiency. An exact correlation between the two is not always found.Aim: The aim of this study is to compare the prevalence of xerostomia and hyposalivation, in HIV positive patients on HAART, HIV positive patients not on HAART and HIV negative patients, attending Empilweni Gompo community health centre (EGCHC) in East London. Study Methods: This is a cross sectional analytical study. Xerostomia and resting & chewing- stimulated salivary flow rates were measured for 150 patients who were from three groups : group 1-HIV negative, group 2-HIV positive not on HAART and group 3-HIV positive on HAART for more than two years. Each group had 50 patients. Xerostomia was measured using a questionnaire and salivary flow rates were calculated after saliva collection over a three minute period. Results: There was significant difference in the prevalences for xerostomia (p=0.006) and less than normal chewing -stimulated flow rate (p=0.041) among the three groups with the HIV positive group not on HAART showing the greatest deficiency. HAART was not found to have a negative effect on salivary function. A statistical significance was also observed while comparing mean resting (p=0.010) and chewing –stimulated (p=0.034) salivary flow rates among the three groups. The mean salivary flow rate of those complaining of xerostomia was found to be significantly lower than that of those who did not have xerostomia (p=0.005). Conclusion: HIV positive patients not on HAART are more vulnerable to salivary gland dysfunction. HAART in itself does not to adversely affect xerostomic perceptions or salivary flow rates.The xerostomia questionnaire is a useful tool in indicating those with possible low salivary flow rates

Submitted by Haroudo Xavier Filho (haroudo.xavierfo@ufpe.br) on 2015-05-19T17:53:52Z No. of bitstreams: 1 Dissertacao_Carlos_Eduardo_PGMT_2014.pdf: 1202449 bytes, checksum: 50023190d007490369919f52f6f388a4 (MD5) / Made available in DSpace on 2015-05-19T17:53:52Z (GMT). No. of bitstreams: 1 Dissertacao_Carlos_Eduardo_PGMT_2014.pdf: 1202449 bytes, checksum: 50023190d007490369919f52f6f388a4 (MD5) Previous issue date: 2014-02-21 / A infecção do GB vírus tipo C (GBV-C) é frequente em pessoas vivendo com HIV/aids devido ao compartilhamento das vias de transmissão. No entanto, se os coinfectados têm uma resposta mais favorável ao tratamento com antiretrovirais do que os monoinfectados ainda é questionado. O objetivo deste trabalho foi verificar a associação entre a contagem de linfócitos T CD4 e carga viral do HIV em pessoas infectadas pelo GBV-C, com ou sem uso de TARV. Foram utilizadas amostras sanguíneas provenientes de pessoas vivendo com HIV/aids e atendidas no Serviço de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Universidade Federal de Pernambuco (UFPE), no período de julho a dezembro de 2011. As amostras sanguíneas, assim como os dados sobre sexo, idade e carga viral do GBV C foram obtidos a partir da soroteca e dos arquivos do Setor de Virologia do Laboratório de Imunopatologia Keizo Asami (LIKA) da UFPE. A contagem de linfócitos T CD4+ e a carga viral do HIV foram obtidas a partir dos prontuários dos pacientes. Trata-se de um estudo descritivo analisado como caso controle, onde foram analisadas 142 pessoas vivendo com HIV/aids há mais de 48 meses de diagnóstico, 86 (60,6%) eram do sexo masculino e 56 (39,4%) do sexo feminino, com média de idade de 43 anos. Foram considerados como caso 34 pacientes coinfectados HIV/GBV-C, sendo 61,8% (21/34) do sexo masculino e 38,2% (13/34) sexo feminino, com média de idade de 41,2 anos. No grupo controle foram 108 monoinfectados pelo HIV, 60,2% (86/108) para o sexo masculino e 39,8% (22/108) para o sexo feminino, com média de idade de 43 anos. No grupo de coinfectados houve uma associação inversa entre a mediana de linfócitos T CD4+ independente do uso de TARV (p 0,006), em qualquer combinação de drogas (p 0,0018) e na combinação de inibidor de transcriptase reversa nucleosídica (ITRN) + inibidor de transcriptase reversa não nucleosídica (ITRNN) (p 0,003). Por outro lado, não foi evidenciada associação entre a contagem de CD4 e a combinação ITRN + inibidor de protease (IP), bem como entre a carga viral do HIV e do GBV-C. Os resultados demonstram que a coinfecção GBV-C/HIV parecer não sofrer interferência da TARV.

As manifestações bucais da AIDS têm sido relacionadas a diversas características clínicas da infecção pelo HIV como decréscimo de células T CD4+, aumento de carga viral e falha terapêutica, entre outras. Os avanços recentes da medicina mostram que a falha terapêutica, nesses pacientes, está diretamente vinculada a mutações na transcriptase reversa (TR) e na protease (PR). O objetivo deste estudo foi descrever, em pacientes HIV+ apresentando falha terapêutica, o perfil de mutações do vírus e o perfil de resistência a antirretrovirais, e correlacioná-los as manifestações bucais da imunodeficiência. Foram acessados prontuários, laudos de genotipagem e informações de bancos de dados digitais de pacientes com AIDS, que se submeteram a genotipagem no Centro de Referência e Treinamento em Doenças Sexualmente Transmissíveis e AIDS (CRT-DST/AIDS), entre 2003 e 2010. Os dados foram transferidos para o Epiinfo, onde foi construído um banco de dados informatizado para posterior análise estatística. O evento lesões orais foi escolhido como variável dependente. Calculou-se o odds ratio para cada variável independente, utilizando intervalo de confiança de 95%. Foram cruzados dados sobre mutações encontradas no vírus e resistência às medicações com a presença e tipo de manifestações bucais. O teste de Bartlett foi utilizado para testar a normalidade dos dados. Para variáveis sem distribuição normal foram aplicados os testes de Mann-Whitney ou Kruskal-Wallis. Para comparação entre frequências e proporções, foi utilizado o Teste de Exato de Fisher ou o Qui quadrado. O nível de significância foi estabelecido como 0,05 ou 5%. A análise de características sociocomportamentais e clínico laboratoriais permitiu verificar que a presença de lesões orais pode ser relacionada estatisticamente a baixas taxas de CD4 (p<0,05), faixa de carga viral (p=0,048) e ao uso prévio de mais de cinco esquemas antirretrovirais diferentes (p=0,021). Verificou-se maior prevalência de lesões virais (75%) e bacterianas (66,7%) do que de lesões fúngicas (37,3%) apenas em pacientes que apresentavam resistência a inibidores de protease (IP) (p=0,02). Foram encontradas 146 mutações diferentes nos pacientes que apresentavam lesões orais, dentre essas, quatro (101E, 20T, 188L, 93L) apresentaram correlação negativa com a presença de lesões orais (respectivamente, p=0,01, p=0,01, p=0,03, p=0,03) e oito (215Y, 118I, 20R, 44D, 71I, 82I E 84V) apresentaram correlação positiva (respectivamente p=0,04, p=0,05, p=0,03, p=0,01, p=0,01, p=0,04, p=0,0004). Subsequentemente, as mutações que apresentaram correlação positiva com a presença de lesões orais foram avaliadas para verificar se sua presença estaria realmente associada a resistência aos ARVs (aos quais seriam supostamente resistentes). Foram excluídas dessa avaliação as mutações 71I e 82I, por apresentarem uma quantidade extremamente pequena de ocorrências. Todas as mutações apresentaram correlação estatística positiva para a resistência aos respectivos antirretrovirais (p<0,05). Em pacientes HIV+, que apresentavam falha terapêutica e manifestações bucais, foram identificadas as mutações 84V e 20R na PR e as mutações 215Y, 44D e 118I na TR e a presença dessas mutações foi associada a resistência a inibidores de protease e inibidores de transcriptase reversa nucleosídeos, respectivamente. / Oral manifestation of AIDS have been associated with several clinical characteristics of HIV infection such as reduction in T CD4+ cells, increase in viral load and treatment failure, among others. Recent advances have shown that treatment failure in these patients is directly linked to mutations in reverse transcriptases (RT) and in proteases (PR). The objective of the present study was to describe the profile of virus mutations and of resistance to antiretroviral drugs in HIV+ patients in treatment failure, and to correlate mutations to the oral manifestations of the immunodeficiency. Patient charts, genotyping results and information from digital databases of AIDS patients, who underwent genotyping at the Sexually Transmissible Diseases and AIDS Training and Reference Center (CRT-DST/AIDS) between 2003 and 2010, were accessed. Data were transferred to the Epiinfo program, in which a computerized database was built for statistical analysis. The event oral lesions was chosen as a dependent variable. Odds ratio for each independent variable was calculated, using a 95% confidence interval. Data found on virus mutations and drug resistance was analyzed to check for correlation with presence and type of oral manifestations. The Bartlett test was used to test normality of data. Mann-Whitney or Kruskal-Wallis tests were used for variables without a normal distribution. The Fisher Exact or Chi-square Tests were used to compare frequencies and proportions. A 0.05 or 5% significance level was established. The analysis of socio-behavioral and clinical-laboratorial characteristics allowed concluding that the presence of oral lesions may be related to statistically low CD4 rates (p<0.05), viral load range (p=0.048) and previous use of more than five different antiretroviral regimens (p=0.021). A higher prevalence of viral (75%) and bacterial (66.7%) lesions in relation to fungal lesions (37.3%) was observed only in patients who were resistant to protease inhibitors (PI) (p=0.02). We found 146 different mutations in patients with oral lesions, among which, four (101E, 20T, 188L, 93L) with a negative correlation with the presence of oral lesions (p=0.01, p=0.01, p=0.03, p=0.03, respectively) and eight (215Y, 118I, 20R, 44D, 71I, 82I E 84V) with a positive correlation (p=0.04, p=0.05, p=0.03, p=0.01, p=0.01, p=0.04, p=0.0004, respectively). Subsequently, mutations with a positive correlation with the presence of oral lesions were assessed to check if their presence would really be associated with resistance to ARVs (to which they supposedly would be resistant to). Mutations 71I and 82I were excluded from this assessment because they had an extremely low frequency. All mutations had a statistically positive correlation for resistance to their respective antiretroviral drugs (p<0.05). Mutations 84V and 20R were identified in PR, and mutations 215Y, 44D and 118I in TR of HIV+ in patients undergoing treatment failure and presenting oral manifestations. Moreover, the presence of these mutations was associated with resistance to protease inhibitors and to nucleoside reverse transcriptase inhibitors, respectively.