Approximately 11.5 million Human Immunodeficiency Virus (HIV)-positive individuals were living in South Africa in 2007, many of whom were infected via mother-to-child transmission. The current study aimed to compare the attentional and concentration functioning of 30 seropositive adolescents on managed anti-retroviral (ARV) programmes, with a comparable group of 71 seronegative adolescents. The results showed that the uncorrected errors on trial 1; self-corrected errors on trial 2; time taken, uncorrected and self-corrected errors on trial 3 of the Stroop Colour-Word Interference Test; and the errors on the Trail Making Test Part B were significantly poorer in the seropositive sample. The results also indicated that the clinical variations in the HIV-positive sample, including the age at which ARVs were commenced; duration of ARV treatment; World Health Organisation (WHO) stage at diagnosis; starting and current CD4+ counts; and starting viral load, but with the exception of the current viral load, impacted significantly on test performance.

HIV-associated peripheral neuropathy (PN), and related functional limitations that affect the quality of life (QoL), may now be one of the most formidable challenges in the health care of people living with HIV (PLHIV). The most common PN is distal sensory polyneuropathy (DSP). It is likely that there is a high prevalence of PN among PLHIV in Rwanda. The available data on the prevalence of PN are poor and there are none on how PN is associated with functional abilities and the QoL of PLHIV, which can guide management. In addition, current management of PN is mostly related to symptomatic management and is mainly pharmacological which may not rehabilitate the neuromuscular function that has been affected by PN. This thesis planned to re-validate and adapt the lower extremity functional scale (LEFS) and the brief peripheral neuropathy screen (BPNS), establish the prevalence of PN, and determine the effects of physiotherapeutic exercises on PN, lower extremity functional limitations and QoL, among Rwandan PLHIV receiving antiretroviral therapy (ART). Methods Study 1 translated LEFS from English to Kinyarwanda, modified it accordingly, and tested its reliability among 50 adult PLHIV on ART. The study also piloted

A research report submitted to the faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Medicine (Pharmacotherapy) / Background: The decision of when to start treatment in an HIV-infected individual has always been problematic as far as CD4 count is concerned. Aims: To determine the clinical outcome of patients who commence HAART at different CD4 cell count levels. Method: Retrospective analysis of records of a cohort of patients who are received ART at workplace wellness clinics in three mines in Limpopo province from January 2003 to December 2009. Patients were divided into three groups based on their baseline, group A (CD4 <100), group B (CD4 101-200) and group C (CD4 201-250) Each patient’s data was analyzed one year after his/her commencement. Results: The percentage of patients who died in group A (16%) differs significantly from the percentage of patients who died in group B (4%) (Fisher exact test p= 0.038) and also differ significantly from the percentage of patients who died in group C (0%) (Fisher exact test p= 0.011). The percentages of patients who developed TB in the three groups are 8%, 8% and 2.9% respectively. When compared statistically, these percentages do not differ significantly (Fisher exact test p=0.059).The percentages of patients with severe bacterial pneumonia in the three groups (2%, 2% and 0% respectively) do not differ significantly (Fisher exact test p=0,276).The percentage of hospital admissions for patients in group A (18%) differ significantly from the percentage in group B (6%) and the percentage in group C (6%) (Fisher exact test p= 0.05). The percentage of patients with weight loss of more than 10% of baseline value in group A (24%) differ significantly from the percentage in group B (4%) (Fisher exact test p= 0.003) and also differ significantly to from the percentage in group C (0%) (Fisher exact test p= 0.001). The percentage of patients with undetectable viral load in group B (89%) is significantly different from the percentage in group A (69%) (Fisher exact test p= 0.03) and is also significantly different from the percentage in group C (61%) (Fisher exact test p= 0.008).The change in mean CD4 cell count was found to be statistically significant within each group (paired t test, p<0.0001), but the mean changes between the three groups (132,141 and 172) respectively, do not differ significantly (ANOVA test). Conclusion: Patients with baseline CD4 cell count of less than 100 have a poor clinical outcome when compared to patients with baseline CD4 cell count of more than 100. Efforts must be made to identify patients early before CD4 cell count fall to below 100 and preferably initiate HAART when CD4 cell count is above 200.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Science in Genetics. Johannesburg, South Africa 2017 / Background: Stavudine (d4T) use is associated with the development of sensory neuropathy (SN), several mechanisms may underlie d4T-induced toxicity, including: (1) Inter-patient genetic variability in the genes modulating the deoxynucleotide triphosphate (dNTP) pool sizes. (2) Variation in intracellular ARV drug concentrations due to genetic variation in drug transporters. In our study we examined the genetic variation in four stavudine transporter genes and seven genes regulating the deoxythymidine triphosphate (dTTP) synthesis and their associations with d4T-induced SN or CD4+ T cell count or mtDNA copy number. Methods: We examined a cohort of HIV-positive South African (SA) adults exposed to d4T, including 143 cases with SN and 120 controls without SN. 26 single nucleotide polymorphisms (SNPs) from the literature were chosen, prioritised on being tagSNPs with minor allele frequency >5% in Kenyan Luhya (a proxy population for the SA Black population); SNP functional effects and suitability for multiplex analysis on the genotyping platform. Genotyping was performed using Sequenom mass spectrometry. A qPCR assay was used to measure the mtDNA copy number. Association of sensory neuropathy, CD4+ T cell count and mtDNA copy number with genetic variants was evaluated using PLINK. Results: All 26 SNPs were in Hardy-Weinberg equilibrium (HWE) in both the cases and controls. SNP rs8187758 of the SLC28A1 transporter gene and a 3-SNP haplotype ABCG2 were significantly associated with CD4+ T cell count after correction for multiple testing (p = 0.043 and p=0.042 respectively), but were not significant in multivariate testing. No SNP remained significantly associated with SN or mtDNA copy number, after correction for multiple testing. Conclusion: Variation in genes encoding molecular transporters of d4T may influence CD4+ T cell counts after ART. This study presents a positive step towards achieving personalized medicine in SA. / MT 2018

A research report submitted to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in the branch of Diagnostic Radiology Johannesburg, 2013 / INTRODUCTION: There is limited information on the radiographic presentation of children eligible to start HAART in resource-limited settings. OBJECTIVES: Determine radiographic patterns on pre-HAART chest X-rays (CXRs) in children, compare findings in immune-suppressed vs. non immune-suppressed children, compare the percentage of children with radiographic features of pulmonary TB to the percentage of children on TB treatment and assess inter-observer agreement between 3 radiologists. METHODS: Children (0-8 years) participating in a cohort study of TB and BCG-IRIS who had an acceptable routine pre-HAART CXR were included. CXRs were independently assessed by 3 radiologists, blinded from clinical data, using a standardised assessment form. All 3 readings were used to create a majority consensus finding during the data analysis phase. RESULTS: Amongst 161 children, the median age at enrolment was 2.3 years (25% (41/161) were <1year), 54% (87/161) were on TB treatment and 65% (100/154) were immune-suppressed. The majority (71%) had an abnormal CXR finding, predominantly air space disease (42%) and parenchymal interstitial disease (21%). Of the sub-group of 112 (70%) CXRs that could be assessed for lymphadenopathy, 75(67%) had one or more features suggestive of TB (74 lymphadenopathy, 2 cavities, 18 miliary infiltration) and 65% (70/107) were immune-suppressed. Statistically significant differences between immune-suppressed and non-immune-suppressed children were noted for features of lymphadenopathy and radiographic pulmonary TB. Amongst the sub-group of 112 CXRs a high percentage 49/75 (65%) were on TB treatment, with 26/75 (35%) not on TB treatment. Inter-observer agreement between all 3 readers was fair for overall abnormal CXR findings (K=0.23), airspace disease (K=0.22), moderate for parenchymal interstitial disease (K=0.54) and slight for lymphadenopathy (K=0.05). CONCLUSION: Among children eligible to start HAART, most (71%) presented with abnormal CXR findings and the majority (67%) had one or more CXR signs suggestive of TB. Of concern was the high proportion of CXRs (30%) that were of insufficient quality to be assessed for lymphadenopathy and the poor inter-observer agreement for lymphadenopathy.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment of the requirements for the degree of Master of Science in Medicine in Pharmacotherapy, Johannesburg, 2011 / Long term antiretroviral therapy (ART) use is known to cause various toxic adverse effects in patients. Hepato-toxicity is one of the most significant adverse effects which have been associated with all antiretroviral therapy drugs in South Africa and worldwide.

Introduction: Stavudine is a commonly used drug in paediatric antiretroviral treatment (ART) regimens. Due to toxicity concerns, however, the drug abacavir has replaced stavudine in first-line paediatric regimens inmany countries.Wedescribe the frequency of stavudine toxicity in children receiving ART at a treatment clinic in Soweto, South Africa. Methods: Data on patient characteristics and outcomes of ART were collected from a cohort of 2222 HIV-infected children initiating ART between 2004 and 2008 when stavudine-containing regimenswere routinely recommended. At several time-points after treatment initiation, we estimate the proportion of children where an attending clinician discontinued stavudine due to lipodystrophy, pancreatitis, lactic acidosis or peripheral neuropathy. Factors associated with stavudine-related toxicities were identified. Results: At ART initiation, most children had advanced disease. The majority initiated an efavirenz/lamivudine/stavudine regimen (n¼1422), and 76% of children remained on their initial ART regimen after a median 19.9 months of ART. Replacement of stavudine due to drug toxicity occurred at a rate of 28.8 per 1000 child years on treatment (95% confidence interval¼23.6–35.2). Rates of toxicity increased with treatment duration (in their first year of ART stavudine was replaced in 0.5% of children, but after 3 years stavudine had been changed to abacavir in 12.6% of children). Toxicity was more common in older children and in girls. Lipodystrophy accounted for 87 of 96 toxic events. Conclusion: Stavudine-associated toxicity resulting in single-drug substitution was uncommon in this cohort, though its frequency increased steadily with ART duration, especially with lipodystrophy. Where drug options are limited, stavudine remains a relatively well tolerated and effective option for children.

Desde a sua descoberta, no início da década de 80, o HIV/aids, constituiu-se como uma doença que ultrapassa os limites da dimensão biomédica, apresentando diversos desafios à sociedade. No Brasil, estima-se que aproximadamente 734 mil pessoas vivem com HIV/aids. Foram desenvolvidas diferentes classes de drogas antirretrovirais para seu tratamento; as quais são eficazes para o controle parcial da replicação viral. Sem a descoberta da cura, é imprescindível que as pessoas vivendo com HIV/aids sigam as recomendações da equipe de saúde, aderindo ao tratamento proposto; aumentando sua qualidade de vida, bem como contribuindo para a diminuição da transmissão do vírus. Durante o tratamento, algumas dificuldades podem surgir, determinando momentos de maior ou menor adesão ao mesmo e os profissionais de saúde, dentre eles, os farmacêuticos, devem estar atentos a estes momentos. Este estudo transversal teve como objetivo analisar a retirada do TARV nos últimos 24 meses e investigar os possíveis fatores que levam a retirada desta medicação de forma irregular na Unidade Especial de Tratamento de Doenças Infecciosas (UETDI) do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo. Participaram 250 pessoas que vivem com HIV/aids que retiram a medicação na Farmácia do local do estudo. Os participantes foram separados em dois grupos: Grupo em Atraso e Grupo Controle segundo seus históricos de dispensação da TARV nos vinte e quatro meses anteriores a realização das entrevistas. Predominaram participantes do sexo masculino (57,6%), com mais de 40 anos (76%), brancos (51,6%), com baixa escolaridade (48,4%), sem parceiro fixo (52,4%), residentes em Ribeirão Preto (63,6%). Todas as variáveis foram relacionadas em um estudo univariado e aquelas com um valor de \"p\" igual ou menor que 0,2 foram selecionadas para análise multivariada. As associações entre variáveis selecionadas e a retirada irregular comparada com a retirada regular, foi estimada pela estimativa com intervalo de confiança de 95%. As variáveis que mostraram associação com a retirada da TARV em atraso foram: fazer uso de outro medicamento além da TARV, apresentar resultado de exame de carga viral como detectável, ter, no início do período analisado, contagem de linfócitos T CD4 menor que 200 células /mm3 e ter baixa adesão como resultado do Teste de Morisky- Green / Since its discovery in the early 80s, HIV / AIDS was established as a disease that pushes the boundaries of biomedical dimension, presenting many challenges to the society. In Brazil, there are almost 734,000 people carrying HIV / AIDS. Different classes of antiretroviral drugs were developed for their treatment, which are effective in partial control of viral replication. Yet incurable disease it is essential that people living with HIV / AIDS follow the recommendations of the health care agents, adhering to the proposed treatment, increasing their quality of life, and contributing to the reduction of transmission of the virus. During treatment, some difficulties may arise, determining moments of greater or lesser adherence, and pharmacists among other health professionals, should be aware of these moments. This cross-sectional study aimed to analyze the withdrawal of ART in the last 24 months, and investigate the possible factors that lead the medication withdrawal erratically on Special Treatment of Infectious Diseases Unit (UETDI) of the Clinics Hospital - School of Medicine of Ribeirao Preto, University of São Paulo. Two hundred and fifty people living with HIV / AIDS got medication in the study site pharmacy. Participants were divided into two groups: Group Control and Group Delay, according to their historical dispensing of ART in twenty-four months prior to the interviews; predominant male participants (57.6%) with more than 40 years (76%), white (51.6%), with low education (48.4%), with no steady partner (52.4%), residents in Ribeirão Preto (63.6%). All variables related in a univariate analysis, and those with a value of \"p\" equal to or smaller than 0.2 were selected for multivariate analysis. The associations between selected variables, and the irregular removal compared to regular withdrawal were estimated with 95% confidence interval. The variables that were associated with the withdrawal of ART arrears, and making use of another drug in addition to HAART, presented results of viral load test as detectable, having the beginning of period analyzed, CD4 lymphocyte count less than 200 cells / mm3, and have low compliance as a result of Morisky- Green test.

Introdução - Deficiências nutricionais derivadas da infecção por HIV são mais severas em crianças em relação aos adultos. Assim, a população pediátrica HIV+ necessita de adequado monitoramento nutricional a fim de direcionar a terapia e garantir melhor qualidade de vida. Objetivo - Caracterizar o perfil nutricional de crianças e adolescentes HIV+ em acompanhamento ambulatorial, segundo antropometria, análise da composição corporal por bioimpedância (BIA) e exames bioquímicos, e avaliar a relação das características nutricionais com o tempo e tipo de terapia medicamentosa. Métodos - Estudo descritivo do tipo transversal, em que 119 pacientes de 6 a 19 anos foram submetidos a antropometria (peso, altura, circunferência da cintura, pregas cutâneas tricipital e subescapular) e análise da composição corporal por BIA. Também foi realizada entrevista com o responsável pelo paciente para avaliação de fatores sócio-demográficos, obstétricos e clínicos. Para definição do histórico clínico e laboratorial, os prontuários foram analisados para obtenção da data do diagnóstico, esquema medicamentoso adotado nos últimos três anos e resultados de exames bioquímicos. Resultados - A avaliação da composição corporal por BIA foi capaz de identificar excesso de gordura corporal total em 30% das meninas e 26% dos meninos. Em contrapartida, 33,6% apresentaram sinais de depleção do tecido adiposo na região tricipital, sugerindo lipoatrofia. Em relação aos parâmetros bioquímicos, 16,7% dos pacientes foram diagnosticados com resistência à insulina, 35,6% com triglicérides elevados, 33,9% com colesterol total elevado, 9,7% com alterações nos níveis de LDL e 81,4% com concentrações reduzidas de HDL. As crianças consistiram no grupo com maior prevalência de dislipidemia e melhor estado imunológico, sugerindo maior vulnerabilidade aos antiretrovirais. Observou-se que os usuários dos esquemas terapêuticos alternativos e tríplices, ambos com inibidores de protease, apresentaram as maiores concentrações médias de triglicérides e, as menores de HDL-colesterol. Conclusões - As classes mais utilizadas no tratamento dos pacientes (inibidores de protease e inibidores nucleosídeos de transcriptase reversa) foram associadas ao prejuízo na manutenção de níveis adequados de lípides séricos, ainda que os medicamentos não tenham sido relacionados a alterações nos parâmetros antropométricos. Contudo, sabe-se que a dislipidemia pode preceder o desenvolvimento de alterações clínicas características da lipodistrofia em portadores de HIV, indicando, a necessidade de se realizar intervenções nutricionais desde o início da doença. / Introduction - Nutritional deficiencies derived from HIV infection are more aggressive in children than adults. Thus, HIV-infected children and adolescents need proper nutrition monitoring to guide the therapy and provide better quality of life. Objective - To characterize the nutritional profile of HIV-infected children and adolescents assisted on outpatient service, according to anthropometry, bioimpedance analysis (BIA) and biochemical parameters, and to analyze the relation among the nutritional characteristics, period and type of antiretroviral therapy (ART). Methods - The study had a cross-sectional design, with 119 patients between 6 to 19 years old. They were submitted to anthropometric measures (weight, height, waist circumference, triceps and subescapular skinfolds thickness) and BIA analysis. The patient\'s caregivers were interviewed to collect social, demographic, obstetric and clinical data, and signed the informed consent. All the records were analyzed to check the diagnosis date, type of drug treatment during the last three years, and biochemical parameters. Results - There weren\'t detected significant alterations in anthropometric measurements, although BIA detected in 30% of girls and 26% of boys a high body fat percentual. However, 33,6% had fat wasting sign in the triceps, which is a lipoatrophy characteristic. Insulin resistance was seen in 16,7% of the patients, high blood triglycerides level in 35,6%, total cholesterol in 33,9%, LDL in 9,7% and low blood HDL level in 81,4%. Children were the group with higher prevalence of dyslipidemia and better immunologic status, so they seemed to be more vulnerable to ART. Patients treated with alternative and triple combination regimens, both with protease inhibitors, had the highest levels of triglycerides and the lowest of HDL. Conclusions - The most administered drugs to the patients (protease inhibitors and nucleoside reverse transcriptase inhibitors) were associated to dyslipidemia, even though these medicines hadn\'t been related to anthropometric deficits. However, lipid metabolism disturbances may precede the development of clinical problems involved in lipodystrophy syndrome in HIVinfected children and adolescents, indicating that nutritional intervention since the beginning of disease is necessary.

Este estudo teve como objetivo analisar as crenças significativas para à adesão ou não dos trabalhadores de enfermagem, que sofreram acidentes do trabalho com exposição a material biológico, ao tratamento quimioprofilático com anti-retrovirais. Trata-se de numa pesquisa embasada no Modelo de Crença em Saúde- MCS, com abordagem de análise de dados quanti-qualitativa, efetuada por meio de cálculos percentuais (dados quantitativos) e análise de conteúdo, estabelecendo-se temas de análise estruturados nas categorias pré-definidas do MCS (dados qualitativos). Coletaram-se os dados utilizando-se entrevista semi-estruturada com registro escrito, dos dados fitos pelos próprios sujeitos, em formulário próprio, sendo todos trabalhadores de enfermagem de uma unidade de tratamento de doenças infecciosas de um hospital universitário do interior do estado de São Paulo. Os resultados encontrados revelaram, que dentre os 41 trabalhadores de enfermagem que compuseram a população estudada, 29 (70,74%) exerciam a função de auxiliar de enfermagem, 10 (24,39%) eram enfermeiros e 02 (4,87%) eram técnicos de enfermagem. O estudo mostrou que 20 (49 %) trabalhadores haviam sido vítimas de um ou até cinco acidentes do trabalho com exposição a material biológico, perfazendo a ocorrência de 38 acidentes. Em 12 (34,30%) casos o trabalhador realizou o tratamento completo com anti-retrovirais; em 15 ( 42,85%) trabalhadores não o completaram e em 8(22,85%) não emitiram informações a respeito. À luz do Modelo de Crenças em Saúde e das categorias preestabelecidas: suscetibilidade percebida, seriedade percebida, benefícios percebidos e barreiras percebidas, extraíram-se os seguintes indicadores: percepção do risco da infecção, comportamento vivenciado pelo acidentado, percepção de mudanças após o acidente, experiência positiva com o uso dos anti-retrovirais e percepção negativa com o uso dos anti-retrovirais.Os resultados revelaram que a principal crença que favoreceu a adesão ao tratamento quimioprofilático foi a suscetibilidade percebida, sendo fundamental para o trabalhador de enfermagem o pensamento acerca do risco de contrair a AIDS. A crença seriedade percebida foi identificada pelo medo de contrair a AIDS, preocupação com a transmissão, sensação de inferioridade.A determinação individual, a letalidade da doença, a ausência de efeitos colaterais e a crença na proteção oferecida pelo tratamento foram os benefícios percebidos pelos sujeitos para adoção de tratamento. Como principal barreira percebida para a nãoadesão do trabalhador ao tratamento, estão os efeitos colaterais ocasionados pelos fármacos, as exigências de horários rigorosos para a ingestão dos medicamentos e o descrédito da ameaça da doença. No estudo realizado evidenciou-se a necessidade em proporcionar atendimento ao trabalhador acidentado considerando seus os aspectos físicos e pessoais, bem como os emocionais, além da implementação de ações que minimizem a ocorrência de tais injúrias. / This study aimed to analyze significant beliefs among nursing workers who were victims of occupational accidents with exposure to biological material, with a view to adherence or not to chemoprophylactic treatment with antiretroviral medication. This research is based on the Health Belief Model-HBM, using a quanti-qualitative approach by means of percentage accounts for quantitative data, while treating qualitative data through content analysis and the establishment of analytical themes structured within the predefined categories of the HBM. Data were collected through semi-structured interviews with nursing workers at an infectious disease treatment unit of a university hospital in the interior of São Paulo, Brazil, which were registered in writing. Results demonstrated that, out of the 41 nursing workers who made up the study population, 29 (70.74%) were nursing auxiliaries, 10 (24.39%) were nurses and 02 (4.87%) were nursing technicians. 20 (49 %) workers had been victims of one to five occupational accidents with exposure to biological material, totalling 38 accidents. In 12 (34.30%) cases, workers followed the complete treatment with antiretroviral medication, while they did not finish treatment in 15 (42,85%) cases and no information was published in 8 (22.85%) of the cases. In view of the Health Belief Model and the pre-established categories: perceived susceptibility, perceived gravity, perceived benefits and perceived obstacles, the following indices were extracted: infection risk perception, victim’s behavior, perception of changes after the accident, positive experience of using antiretroviral medication and negative perception of using antiretroviral medication. The results revealed that the main belief determining adherence to chemoprophylactic treatment was perceived susceptibility, considering the risk of getting AIDS as fundamental for nursing workers’ performance. The belief on perceived gravity was identified by the fear of getting AIDS, worries about the transmission, feeling of inferiority. The subjects perceived the following benefits: individual determination, lethality of the disease, absence of collateral effects and belief in the protection offered by treatment. The main obstacles perceived for workers’ non adherence to treatment were collateral effects caused by the medication, need for medication intake at strict times and discredit in the disease as a threat. This study disclosed the need to consider physical, personal and emotional aspects of worker casualties when delivering care to the workers and to implement actions that minimize the occurrence of these injuries.