Magister Scientiae Dentium - MSc(Dent) / The initiation of highly active antiretroviral therapy has shown to result in successful suppression of viral replications followed by an increase in CD4 lymphocytes, a partial recovery of T-cell specific immune responses and decrease susceptibility to opportunistic pathogens. Aim: The aim of the present study was to determine the prevalence of oral lesions in patients before and after undergoing HAART. Methods: The study design was longitudinal and descriptive, investigating the prevalence of oral lesions presenting in HIV/AIDS patients at baseline, 3 and 6 months after taking HAART. A convenience sample size of 200 participants was targeted. Results: 210 HIV positive patients participated at baseline. At 3 months, 96 (46%) and at 6 months, 52 (25%) were available for review respectively. At baseline 210 HIV positive patients were recruited into the study from three hospitals. Two infectious disease hospitals belonged to the City of Harare and the other is a government hospital. Just over two thirds were female (64.3%) and the age ranged as follows: 21-30 (17%); 31-40 (44%); 41-50 (26% and 51-60 (9%).Discussion: HAART appears to be effective in reducing the prevalence of oral lesions in persons with AIDS likely due to the immunological reconstitution. Oral candidiasis remains the most prevalent oral opportunistic infection in immuno-suppressed individuals and hence its important predictive value for immuno-suppression defined as CD4-cell count level <200/mL of blood. All oral lesions strongly associated with HIV infection with the exception of non-Hodgkin’s lymphoma were diagnosed at baseline. CD4 cell count level increased after initiation of HAART. T-lymphocytes that are formed after the introduction of HAART may not provide sufficient protection against some lesions like parotid gland disease and HPV conditions (planar warts). HAART failure was detected in some patients who had negative CD4-cell count at 6 months compared to the baseline parameters. Conclusions: HIV-positive patients experience oral pain during the course of their disease, eating, drinking and swallowing. Further longitudinal studies are required in order to ascertain the prevalence of these lesions at three and six months and the effect of HAART.

Magister Public Health - MPH / Background: The hallmark of HIV infection is immunosuppression which predisposes to unusual infections and malignancies generally known as opportunistic diseases (ODs). Globally, ODs are the major cause of morbidity and mortality in people living with HIV (PLHIV). Since the advent of Highly Active Antiretroviral Therapy (HAART), a significant decline in AIDS progression and ODs has been observed globally. However, most of the evidence suggesting sustained decline in AIDS progression and ODs has come from high-income settings with relatively less burden of ODs in the pre-HAART era. The findings of studies in high-income settings may not be generalizable to resource-limited settings. Lack of information regarding the burden of ODs in HAART-experienced populations in Nigeria and the risk factors for their occurrence has made it difficult to fully assess the sustained efficacy of HAART in the country. The aim of this study was to investigate the prevalence of and risk factors for HIV-related opportunistic diseases amongst HAART patients at the Federal Medical Centre (FMC) in Owerri, Nigeria. Study design and setting: A quantitative, cross-sectional descriptive and analytical study was conducted with 354 adult HIV-infected patients 15 years and above, who were on HAART for a minimum of 12 weeks at the HIV clinic of the FMC, Owerri, South-east Nigeria. Patients currently manifesting an OD whose onset ante-dated the commencement of HAART were excluded. The participants were recruited by simple random sampling. Data collection: Using a structured questionnaire, data was collected by clinicians through interviews, physical and laboratory examinations for patients that provided informed consent and met the study criteria. The questionnaire captured patient’s socio-demographic information and other relevant clinical/laboratory data. Data Analysis: The data was analysed using Epi info version 3.5.1 and Open Epi Version 2.2.1. Descriptive statistics for HIV-related ODs were carried out using percentages and frequencies tables for categorical variables and means (SD) or medians (IQR) for numerical variables. In univariate analysis, the Chi-square test was used to determine significance of association between OD and socio-demographic and clinical variables while the Student "t"-test was used to compare group means. Logistic regression model (multivariate analysis) was used to determine the independent risk factors for the occurrence of ODs using parameters that had a p-value of <0.25 on univariate analysis. All reported p-values <0.05 were considered statistically significant. Results: The mean age of the participants was 41.1 ± 10.0 years; and females were in the majority (65.8%). Over 40% of them were rural dwellers, 50.4% belonged to the lower socioeconomic class, and 55% had a monthly household income less than 20,000 Naira. Fifty percent (50%) of them had advanced immunosuppression at first presentation. The median duration of HAART (3 years) paralleled the median duration of HIV diagnosis (3.4 years) and HAART adherence rate was 78%. The overall prevalence of ODs was found to be 22.4%. Among the 76 patients diagnosed with ODs, the leading conditions were candidiasis (38.2%), TB (34.2%), dermatitis (25%), chronic diarrhoea (6.6%) and sepsis (6.6%). The independent risk factors for the occurrence of ODs were household income less than 20,000 Naira (Adjusted odds ratio [AOR] = 2.4, 95% CI 1.1-5.1), HIV duration of less than 3 years (AOR= 2.1, 95% CI 1.1- 4.2), advanced WHO clinical stage at baseline (AOR= 8.1, 95% CI 4.0-16.4), baseline haemoglobin less than 10 g/dl (AOR= 2.9, 95% CI 1.3-56.1), current CD4 cell count less than 200 cells/μl (AOR= 3.0, 95% CI 1.14-6.2), and HAART non-adherence (AOR= 5.4, 95% CI 2.6-11.2). Past history of TB was found to be a strong predictor of TB (AOR= 5.3, 95% CI 1.4-20.2). Conclusions: Opportunistic diseases are common in patients receiving HAART in Nigeria and candidiasis and TB remain the leading conditions. Late presentation and HAART non-adherence are among the strongest risk factors for ODs in patients receiving HAART. Others include duration of HIV diagnosis less than 3 years, presence of anaemia at the time of first presentation and having a low CD4 cell count while on HAART. Beyond these clinical risk factors, poverty increases the risk of developing an OD during HAART and may emerge a strong determinant of HIV-related ODs in developing countries. Recommendations: A high index of suspicion for ODs remains necessary in HAART patients. Health education on HIV screening and early presentation should be intensified. PLHIV who are anaemic before commencement of HAART, those with low CD4 cell count despite HAART use, and low-income earners should become target groups for a more aggressive evaluation for ODs. Prophylaxis for TB and fungal infections in the absence of active disease should be widely implemented in developing countries. HAART adherence should be intensified.

The introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease in the mortality and morbidity associated with the acquired immunodeficiency syndrome (AIDS). Several problems are associated with HAART and include high costs of treatments, poor availability of drugs in low-income countries, poor compliance, severe adverse effects and drug resistance. Therefore, the focus of current research is the development of new antiretroviral drugs, improved treatment strategies and the discovery of new drugs derived from plants. Green tea (GT) and its active constituent epigallocatechin gallate (EGCg) have been found to be protective against cancer, cardiovascular and neurodegenerative diseases and were found also to have antimicrobial, antimalarial and more importantly antiviral activity. EGCg, in vitro has been shown to inhibit the human immunodeficiency virus (HIV) viral enzymes reverse transcriptase and protease, destroy viral particles and interfere with the attachment of gp120 to cellular receptor CD4. The aims of this study were firstly to investigate the in vitro antiretroviral activity of GT and EGCg on the LP-BM5 defective murine leukemia virus (MuLV) that induces a disease in C57BL/6 mice similar to AIDS in humans and secondly to investigate the effects of GT and EGCg on the in vitro cytotoxicity and antiretroviral activity of current antiretroviral drugs zidovudine (AZT), indinavir (IDV), hydroxyurea (HU) and chloroquine (CQ). To achieve the above aims an in vitro model that represents cell-to-cell spreading of the LP-BM5 MuLV was developed. Firstly the presence of the LP-BM5-defective virus in the BM5 cell line was confirmed using transmission electron microscopy (TEM) to identify viral particles, PCR and RT-PCR were used to determine the presence of viral DNA and RNA respectively and viral infectivity was confirmed in C57BL/10 mice. The cytotoxicity of each drug and combination was evaluated with the MTT assay in the SC-1 cell line, the predominant cell type in the in vitro cell culture model. GT was the least cytotoxic, followed by AZT, IDV, EGCg, HU and CQ. Co-cultures (BM5:SC-1, 1:10000) that represented cell-to-cell transmission of the virus were established. Real time PCR for proviral DNA revealed that IDV, AZT and HU completely suppressed, CQ dose dependently reduced while GT and EGCg had no effect on viral transmission. Findings using AZT and IDV thus validated the use of this in vitro co-culture model for first line screening of new drugs and plant extracts. The effect of GT or EGCg in combination with AZT, IDV, HU or CQ was also evaluated as GT or EGCg could enhance the antiretroviral effects or decrease cellular toxicity of these drugs. For GT with AZT a mix of synergism and antagonism on cell toxicity was observed with little to no effect on the antiretroviral activity of AZT. Antagonism on cell toxicity was observed for GT with IDV, with no effect on the antiretroviral activity of IDV. In contrast EGCg significantly reduced the antiretroviral activity of IDV. A strong antagonistic effect was observed for GT with HU, with GT reducing the antiretroviral effect of HU. For combinations of AZT with EGCg and HU with EGCg a similar effect was observed as for AZT and HU respectively combined with GT. Synergism in cytotoxicity was observed between GT and CQ associated with a significant decrease in viral loads while EGCg combined with CQ had an opposite effect at higher concentrations. In conclusion, the in vitro co-culture model of BM5 and SC-1 cells was successfully used to evaluate combinations of GT and EGCg with AZT, IDV, HU and CQ. Interesting and often contradicting effects were observed, such as seen for IDV in combination with GT and EGCg as well as CQ in combination with GT and EGCg. These effects may be of clinical relevance and further investigation is warranted. / Dissertation (MSc)--University of Pretoria, 2009. / Anatomy / unrestricted

Objetivo: El objetivo del estudio es determinar la concordancia entre las escalas PROCAM (Prospective Cardiovascular Münster) y Framingham en pacientes receptores de Tratamiento Antirretroviral de Gran Actividad (TARGA). Método: Estudio transversal analítico en población masculina VIH positiva receptora de TARGA dentro de un hospital de referencia nacional ubicado en Lima, Perú. Para evaluar la concordancia entre ambas escalas se empleó el método gráfico de Bland y Altman, correlación con el coeficiente de Pearson y acuerdo entre pruebas mediante el coeficiente de Kappa. Resultados: Enrolamos 111 personas, con edad promedio de 47,0 años. El 76,6% presentó dislipidemia. Los triglicéridos evidenciaron una media de 265,0 mg/dL. La distribución de pacientes en riesgo cardiovascular bajo, moderado y alto fue de 81,2%, 13,6% y 5,4%, según PROCAM y de 71,2%, 25,2% y 3,6% según Framingham respectivamente. Según el método de Bland y Altman, la concordancia fue adecuada en valores bajos y se fue perdiendo en riesgos altos. El coeficiente de Pearson mostró fuerte correlación (r=0,87 y P<0,05) y el coeficiente de Kappa fue de 0,56 (p<0,001). Conclusiones: La concordancia existente a riesgos bajos se va perdiendo a medida que el riesgo se va incrementando. Existe fuerte correlación entre ambas escalas. Se recomienda realizar más estudios que permitan conocer qué escala es la más óptima para ser utilizada en población adulta VIH positiva receptora de TARGA. / Objective: The aim of the study is to determine the concordance between the PROCAM (Prospective Cardiovascular Münster) and Framingham scales in patients receiving highly active antiretroviral therapy (HAART). Method: A cross sectional study was conducted in HIV-positive male population who use HAART in a national reference hospital located in Lima, Peru. To evaluate the concordance between the two scales the graphic method of Bland and Altman was used, for the evaluation of the correlation we used the Pearson coefficient and to measure the agreement we use the kappa coefficient. Results: 111 patients were enrolled, with an average age of 47.0 years. The 76.6% had dyslipidemia. Triglycerides showed an average of 265.0 mg/dL. The distribution of patients according to the risk was low, moderate and high, 81.2%, 13.6% and 5.4% respectively for PROCAM and 71.2%, 25.2% and 3.6% for Framingham. According to the graphic method of Bland and Altman, the concordance was adequate in low values and was lost as the risk score increased. Pearson's test found a strong correlation (r = 0.87 and P <0.05) and the kappa coefficient was 0.56 (p<0,001). Conclusions: The agreement we found at low risk decreases as the risk increases. Strong correlation was found between the two scales. We recommend further studies in order to know which scale of cardiovascular risk is the most optimal scale for clinical practice among HIV population who receive HAART.

In the gut-associated lymphoid tissues, Th17 cells mediate mucosal homeostasis and inflammation. During HIV infection, Th17 cells become depleted and functionally impaired, which is implicated in the pathogenesis of chronic inflammation in patients treated with highly active antiretroviral therapy. IL-7 is a cytokine that mediates homeostatic responses in T lymphocytes, such as proliferation and survival, which are dysregulated during HIV infection. Whether similar dysregulation occurs in Th17 cells has yet to be reported. IL-7 receptor α (CD127) expression and IL-7 responses were therefore measured in blood-derived Th17 cells from uninfected individuals and effectively treated, HIV-infected individuals by flow cytometry. Th17 cells from uninfected individuals expressed CD127 and, in response to IL-7, exhibited phosphorylation of STAT5, upregulation of Bcl-2, and proliferation. During HIV infection, expression of CD127 and pSTAT5 in Th17 cells was comparable to that observed in cells from uninfected individuals. Interestingly, expression of Bcl-2 was upregulated while proliferation was dramatically impaired. These findings may provide further insight into the mechanisms by which Th17 cells fail to become restored during HIV infection.

No description available.

Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence predict response to HAART as measured by CD4 count, weight gain and functional status in a cohort of patients in Roma, the Kingdom of Lesotho. Method: Data were collected from a computerised database of the Antiretroviral Centre of the hospital. A cohort of 300 subjects was identified from hospital records from January 2007. Each of these subjects was followed up over a period of 12 months with data obtained for at least two visits within the 12-month span. Data were obtained on weight and CD4 at baseline, three months and also at six and 12 months, and data for haemoglobin were obtained only at 12 months. Variables that may be potential confounders were identified and univariate and multivariate logistic regression analyses were carried out to establish differences independent of confounding factors for the combined endpoints, as well as for each endpoint separately. Results: Three-hundred patient records were analysed. Approximately 70% of the patients had a CD4 increase of at least 150 cells over baseline values at the end of the review period and in 52.3% of the patients an increase in weight of 10% over baseline measurements was seen. Seventy-nine patients (26.3%) had a haemoglobin level of at least 14g/dL at 12 months, regardless of baseline values or gender. The inclusion of Zidovudine (AZT) in treatment regimens was found in 73% of the patients and in multivariate analysis AZT was associated with not having anaemia at the end of the review period. However there was a slight reduction in haemoglobin level in the first two to three months of therapy in comparison with both Stavudine (d4T) and Tenofovir (TDF) but not significant enough to result in clinical anaemia. Baseline CD4 values were similar for all treatments options but dissimilar in other outcome variables and continued to vary significantly throughout the review period. The outcomes of multivariate analyses suggest that the male gender appears to have better response to HAART as seen in each of the multivariate models. The most important determinant of haemoglobin response was baseline haemoglobin values. In the haemoglobin-associated multivariate model, HAART is associated with an increase in haemoglobin over baseline values. A history of TB prior to HAART was a major factor in weight response and it is thought to be as a result of IRIS, which is the unmasking of latent infections as the immune system reconstitutes. CD4 values have no direct influence on weight however, but an increase in weight was observed in all therapy groups. Conclusion: Clinical and immunological parameters can be used to monitor response to HAART and predict treatment outcomes. These parameters can be organised into monitoring tools that will be useful in resource-limited areas. This study suggests that AZT-containing regimens appear not to result in anaemia and that symptomatic anaemia might need additional investigation. Treatment with TDF appeared to have shown the best possible response pattern more but patients on TDF therapy will have to be included in the study to justify this observation. / Dissertation (MSc)--University of Pretoria, 2012. / Clinical Epidemiology / unrestricted

Objectives The study aims to describe the socio-demographic characteristics, clinical outcomes of the patients in the Gauteng public sector roll-out programme and establish the association between these. There are contradictory results from international studies on these associations, in the absence of SA results. Methods This is a retrospective cohort, exploratory, secondary data, record review study and a comparison between two sites. Routinely collected socio-demographic data and clinical data were used to establish the impact of socio-demographic factors on response to HAART. This was collected for patients who enrolled from April 2004 to August 2004. Chris Hani Baragwanaath (CHB) had 494 records, Helen Joseph (HJ) had159 records collected. Exposure variables (age, sex, marital status, education level, residential area, employment, baseline viral load and baseline cd4 count). Outcome variables were (CD4 and Viral load at 3 months, 6 months and 12 months). Data Analysis T tests were used for comparing means; logistic regression was used to find the effect of ordered exposure variables and binary outcome. Chi square and fishers exact were used to find frequencies and association between the categorical variables. Regression was used to find the association between the continuous exposure variables and the continuous outcome variables. In a multivariate model, to assess the effect of the exposure variables to the outcome variables Multivariate regression was used. Statistical significance was assessed at the 5% significance level, giving 95% confidence interval. Results The majority of the patients (653) were female, African, unemployed and were literate. At CHB, at the end of the first year, three quarters were still on treatment however; just under a fifth (19%) had died. The majority responded well to treatment and had a mean baseline CD4 count of 58.9cells/mm3 (CHB) and 78.4cells/mm3 (HJ) and mean CD4 count of 245 (CHB) and 268 (HJ) after 12 months. increasing age, and being widowed, lowers the immunological response. Employment, education, sex and had no impact on response. Conclusion • There is positive virological and immunological response to HAART in Gauteng ARV roll-out programme despite the low socio economic status of the majority of the patients. • Provision of free antiretroviral drugs and access to the disability grant has assisted in mitigating the effects of HIV/ AIDS on the socio-economically disadvantaged. • The elderly and the widowed might need close monitoring as their response appears to be lower than the others. • The group with no schooling is not well represented in this sample; the question is whether the HIV/AIDS prevention messages and treatment is accessible for this group. This needs further research.

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 Physiotherapy. Johannesburg, 2015 / The Human Immunodeficiency Virus (HIV) has been found to cause muscle weakness, wasting and peripheral neuropathies. The specific relationship between lower limb muscle strength and lower limb function in HIV positive patients on Highly Active Antiretroviral Therapy (HAART) has not been examined. The aims of the current study were to establish lower limb muscle strength in HIV positive patients on HAART, establish lower limb muscle strength in HIV negative people, compare lower limb muscle strength between patients who are HIV positive on HAART and HIV negative people, establish lower limb function in patients who are HIV positive on HAART and to establish the relationship between lower limb muscle strength and lower limb function in patients who are HIV positive on HAART. A cross-sectional, descriptive study design was used. Dynamometry was used to measure lower limb muscle strength. The lower Extremity Functional Scale (LEFS) was used to determine lower limb function. A pilot study was done to establish the feasibility and proficiency required to perform hand held dynamometry. Intra and inter-rater reliability were also determined during the pilot phase. Intra and inter-rater reliability were high for the raters' measurement of lower limb muscle strength using a dynamometer with 'r' values of 0.97. For HIV positive patients on HAART, 19% (n=22) were in the age band 45-49years, whereas 33% (n=10) of HIV negative subjects were in age interval 25-29 years. Those over 45 years who were HIV positive on HAART constituted 57% (n=64) of the sample. The mean muscle strength obtained ranged from 9.30kg/m2 in ankle dorsiflexors to 15.80kg/m2 in hip extensors in HIV positive people on HAART for an average of 4 years while knee flexors generated 11.81 kg/m2 and knee extensors generated 15.36kg/m2 in this cohort.Jn the HIV negative matched group, the mean muscle strength ranged from 11.20 kg/m2 in ankle dorsiflexors to 17.70 kg/m2 in hip extensors while knee flexors generated 12.65kg/m2 and knee extensors generated 17.07kg/m2. The majority 78% (n=88) of HIV positive patients on HAART had no difficulty with lower limb function while 22% (n=17) had difficulty. Only 2% (n=2) of HIV positive patients on HAART had quite a bit of difficulty with lower limb functional activities after measurements using the Lower Extremity Functional scale (LEFS). A multiple linear regression showed that there was a positive correlation coefficient of r=0.71 (p-value= 0.00) between lower limb muscle strength and lower limb function. The coefficient of determination 0.50 means that 50% of the changes in lower limb function are attributable to lower limb muscle strength. Gender, employment status and mode of transport also positively affected lower limb function. A detailed regression model showed that lower limb ankle plantar flexors contributed the most to lower limb function in this cohort. This is contrary to International literature which states that hip and trunk muscles are the most active in HIV negative people during lower limb functional activities. That plantar flexors contribute the most in lower limb functional activities instead of hip and trunk muscles confirms the existence of proximal weakness in this cohort which was established by other researchers. This study highlighted that 50% of lower limb function is a result of lower limb muscle strength in HIV positive people on HAART attending an outpatient clinic in Mutare, Zimbabwe. Ankle plantar flexors instead of hip flexors were the most active muscle group in lower limb functional activities in this cohort. It therefore means exercise prescription to activate/strengthen hip flexors and other proximal muscles will improve this population's lower limb functional activities since progressive resisted aerobic exercises have been proved to strengthen muscles. / AC2016

Made available in DSpace on 2016-01-26T12:51:30Z (GMT). No. of bitstreams: 1 lucianaventuracardoso_dissert.pdf: 3002304 bytes, checksum: 02b40ec95b83f50e5985da825d9687ba (MD5) Previous issue date: 2011-06-22 / Was described the epidemiology of intestinal parasites in patients from an AIDS reference service in the northeastern São Paulo, Brazil Retrospective evaluation of all HIV-1/AIDS positive patients whose Hospital de Base/São José do Rio Preto laboratorial analysis was positive for enteroparasites after diagnosis of HIV-1 infection, from January 1998 to December 2008. Statistical analysis was performed using version 2.4.1 statistical software R. The level of significance adopted was 5%. The most frequent protozoan was Isospora belli (4.20%), followed by Giardia lamblia (3.5%), Entamoeba coli (2.80%) and Cryptosporidium parvum (0.28%). The Ancylostoma duodenale was the most helminths frequently detected (1.40%), while Taenia saginata and Strongiloides stercoralis were found in 0.7% of the samples. Results showed that diarrhea was significantly associated with giardiasis and isosporiasis. However, no association was observed between CD4+ cell counts, viral load and the characteristic of any particular parasite. Our data may serve as a starting point for further comparisons with various Brazilian regions and other developing countries. The data may provide important clues to the future understanding, prevention and control of enteric parasites around the world. / Foi descrita a epidemiologia de enteroparasitoses em pacientes de um serviço de referência de AIDS no noroeste paulista, Brasil. Durante o período de janeiro de 1998 a dezembro de 2008 foi realizado este estudo retrospectivo por meio da análise dos prontuários dos pacientes diagnosticados com HIV-1/AIDS atendidos no Ambulatório de Doenças Infecto-parasitárias do Hospital de Base, São José do Rio Preto, São Paulo. As análises estatísticas foram realizadas usando a versão 2.4.1 do software estatístico R. O nível de significância adotado foi de 5%. O protozoário mais frequente foi o Isospora belli (4,20%), seguido da Giardia lamblia (3,5%), Entamoeba coli (2,80%) e Criptosporidium parvum (0,28%). O Ancylostoma duodenalis foi o helminto mais detectado (1,40%), enquanto que a Taenia saginata e o Strongiloides stercoralis foram observados em 0,7% das amostras. Os resultados mostraram que a diarreia foi significativamente associada com giardíase e isosporíase. Entretanto, nenhuma associação foi observada entre as contagens de células T CD4+, carga viral e a característica de qualquer parasito em particular. Nossos dados podem servir como ponto de partida para futuras comparações em diversas regiões do Brasil e outros países em desenvolvimento. Os dados obtidos podem direcionar futuras investigações importantes para o entendimento, prevenção e controle de enteroparasitoses no paciente com AIDS em todo o mundo. Palavras Chave: Epidemiologia, HIV-1, AIDS, enteroparasitos, HAART, Brasil.