Submitted by Suzana Dias (suzana.dias@famerp.br) on 2018-11-09T18:53:26Z No. of bitstreams: 1 RenatoFerneda_dissert.pdf: 585980 bytes, checksum: 7c6b97dc0f3805fe789d0fdbee741928 (MD5) / Made available in DSpace on 2018-11-09T18:53:26Z (GMT). No. of bitstreams: 1 RenatoFerneda_dissert.pdf: 585980 bytes, checksum: 7c6b97dc0f3805fe789d0fdbee741928 (MD5) Previous issue date: 2018-04-27 / Although the antirretroviral therapy, in spite of having reduced the mortality for AIDS and increased the lifespan of the HIV bearers, it can contribute to the arrise of adverse long time effects, besides renal ones. The tenofovir (TDF), a first line antirretroviral (ARV) for treatment, has low general toxicity. TDF can take to moderate reduction in glomerular filtration rate (GFR) and a larger prevalence of renal tubular dysfunction (RTD) when compared to those patients who are not on therapy of this medication. The decline of the renal function found in the patients can vary from mild to chronic injuries or a simple reduction in GFR. The mechanism of RTD is not completely understood, and it has been attributed to the mitocondrial lesion in the proximal tubule cells caused by the increasing of the intracelular TDF concentration. Aditionaly, host´s genetic polymorphisms have been considered one of the TDF concentration increasing causes. RTD can be characterized concisely by the deficiency in the solutes reabsorption as bicarbonate, uric acid, phosphate, glucose and low weight molecular proteins. Objectives: verify the prevalence of RTD in the HIV bearers on TDF treatment, identify the risk factors associated and compare the 24-hours urine methods with the serum creatinine and its clearance for the RTD identification. Methods: longitudinal prospective study, performed in the Complexo de Doenças Transmissíveis em São José do Rio Preto/SP, between january 2011 to december 2015. Results: 163 patients were included in the study, in which 106 (68,4%) didn't use TDF and 57 (31,6%) used TDF. RTD occured in 8 patients that used TDF, a prevalence of 14%. The patients age was identified as significant risk factor for the development of RTD. The proteinuria (average 109,2mg/24h) and the phosphaturia (average 791,9mg/24h) were significant for the diagnosis of RTD. Conclusions: the prevalence of RTD was 14%. The age was determined as risk factor for RTD, mainly in patients over 60 years-old. Phosphaturia and the proteinuria showed the greatest diagnosis sensibility for RTD, respectively. The serum creatinine and phosphorus concentration, the creatinine clearance and the stand alone hyperproteinuria should not be used as diagnosis predictors for RTD. / A TARV, apesar de ter reduzido a mortalidade por AIDS e aumentado a expectativa de vida dos portadores de HIV, pode contribuir para o aparecimento de efeitos adversos de longo prazo, inclusive renal. O tenofovir (TDF), antirretroviral (ARV) de primeira linha para o tratamento, tem baixo perfil geral de toxicidade. No entanto, pode levar a uma moderada redução na taxa de filtração glomerular (TFG) e uma maior prevalência de disfunção tubular renal (DTR) quando comparado àqueles pacientes que não o utilizam. O declínio da função renal encontrado nos pacientes podem ser injúrias agudas, crônicas ou uma simples redução na TFG. O mecanismo da DTR não é totalmente conhecido; atribui-se à lesão mitocondrial nas células dos túbulos proximais pelo aumento da concentração do TDF intracelular, além da suspeita da influência de polimorfismos genéticos dos hospedeiros. Pode ser resumidamente caracterizada pela deficiência na reabsorção de solutos como bicarbonato, ácido úrico, fosfato, glicose e proteínas de baixo peso molecular. Objetivos: Verificar a prevalência da DTR nos portadores de HIV em uso de TDF; identificar os fatores de risco associados e comparar os métodos de Urina de 24 horas com a creatinina sérica e o clearance para a sua identificação. Casuística e método: estudo longitudinal prospectivo, com 163 pacientes, realizado no Complexo de Doenças Transmissíveis em São José do Rio Preto/SP, no período de janeiro de 2011 a dezembro de 2015. Resultados: Foram incluídos 163 pacientes no estudo, dos quais 106 (68,4%) não utilizaram TDF e 57 (31,6%) utilizaram TDF. A DTR ocorreu em 8 pacientes que utilizaram TDF; uma prevalência de 14%. A idade dos pacientes (média de 43,9 anos) foi identificada como fator de risco significante para o desenvolvimento da DTR. A proteinúria (média 109,2mg/24h) e a fosfatúria (média 791,9mg/24h) foram significantes para o diagnóstico da DTR. Conclusões: A prevalência da DTR foi de 14%. A idade foi determinada como fator de risco para a DTR, principalmente, na faixa acima dos 60 anos. Os exames laboratoriais que mostraram a maior sensibilidade diagnóstica para a DTR foram a fosfatúria e a proteinúria, respectivamente. A creatinina sérica, o fósforo sérico, o clearance de creatinina e a hiperproteinúria isolada não mostraram sensibilidade como preditores diagnósticos para a DTR.

Highly-active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected individuals. Unfortunately it has also been associated with impaired functional capacity and development of metabolic perturbations which increases health risk. This study tested the hypothesis that a combined cardiorespiratory and resistance exercise training (CARET) intervention may result in significant health benefits in HIV-infected individuals receiving HAART. Thirty-seven HIV-infected men and women, predominantly of lower socioeconomic status (SES), were recruited and randomly assigned to: 1) a group of moderate-intensity CARET for three months or 2) a control group receiving no exercise intervention for three months. At baseline and following the intervention, physical characteristics (body weight, body mass index, waist circumference, and blood pressure), physical fitness variables (estimated VO2max and one repetition maximum for upper and lower body), metabolic variables (fasting glucose and serum lipids), immune functioning (CD4+ T Cell count, CD4/CD8 ratio, and HIV RNA viral load), and quality of life (SF-36 Health Survey) were measured. Exercise participants evidenced increases in estimated VO2max (21%, p < 0.01), upper body strength (15%, p < 0.05), and lower body strength (22%, p < 0.05), while showing reductions in waist circumference (-2%, p < 0.05), and fasting glucose (-16%, p < 0.05). While the control group showed a significant decrease in CD4+ T cell count (-16%, p < 0.05) from baseline, the exercise group maintained a more stable count following training (-3%, p = 0.39). Finally, the exercise participants showed self-reported improvements in physical (11%, p < 0.03) and mental (10%, p < 0.02) quality of life. In conclusion, our study demonstrated that a three-month supervised and moderate intensity CARET program performed three times a week, can result in significant improvements in physical characteristics, physical fitness, metabolic variables, and physical and mental quality of life. Furthermore, the same intervention resulted in more favorable immunological responses following training in HIV-infected individuals of lower SES. Key words: Highly active antiretroviral therapy, HIV, combined aerobic and resistance exercise training, cardiorespiratory fitness, muscular strength, and immune functioning.

Background: Some studies have suggested that the risk of preeclampsia in HIV positive pregnant women has increased since the use of HAART became routine. There is also a concern that HIV positive women on HAART have a higher risk of adverse fetal outcomes compared to HIV negative women. Methods: In this matched retrospective cohort study, the risk of preeclampsia and adverse fetal outcomes was examined in 91 HIV positive pregnant women receiving HAART and 273 HIV negative pregnant women. Multivariate logistic regression models were used to adjust for confounding factors. Results: The risk of preeclampsia and preterm birth did not differ significantly between HIV positive and HIV negative women. HIV treated with HAART was an independent predictor for giving birth to a low birthweight baby. Conclusions: HIV positive women on HAART do not have a higher risk of preeclampsia. They do however have a higher risk for lower birthweight infants.

Background: Some studies have suggested that the risk of preeclampsia in HIV positive pregnant women has increased since the use of HAART became routine. There is also a concern that HIV positive women on HAART have a higher risk of adverse fetal outcomes compared to HIV negative women. Methods: In this matched retrospective cohort study, the risk of preeclampsia and adverse fetal outcomes was examined in 91 HIV positive pregnant women receiving HAART and 273 HIV negative pregnant women. Multivariate logistic regression models were used to adjust for confounding factors. Results: The risk of preeclampsia and preterm birth did not differ significantly between HIV positive and HIV negative women. HIV treated with HAART was an independent predictor for giving birth to a low birthweight baby. Conclusions: HIV positive women on HAART do not have a higher risk of preeclampsia. They do however have a higher risk for lower birthweight infants.

Background: Since the beginning of 21st century, several Asian countries started implementing their national free antiretroviral therapy (ART) programs to tackle one of the most striking public health issues in Asia – HIV/AIDS. Despite the efforts being made, the treatment coverage remains as low as 44% in 2010. Previous studies have identified financial constraint is a major barrier in accessing ART and an important reason of poor ART adherence in Asia. The purpose of this literature review is to explore the extent of financial burden experienced by people living with HIV (PLHIV) where free ART policy is implemented, and to provide valuable information for policy-making in reducing financial barriers and improve uptake of ART. Methods: Literature search was performed by entering keywords in PubMed and Medline. Articles were screened and selected for in-depth review according to the inclusion and exclusion criteria. A process on data synthesis was performed on the final eligible papers. Results: Five studies from four Asian countries describing the out-of-pocket health expenditure incurred by PLHIV during the delivery of ART were included in this review. Findings: Out of all direct medical costs, the cost of drug was most important in contributing to the total costs for patients without health insurance, while the cost of transportation was more important for patients covered by health insurance. Direct medical costs increased with advancing stage of disease. Rural patients would have spent up to 1,173% of their monthly income per capita, or more than 100% of their total household expenditure even when ART was provided free-of-charge. Patients have also highlighted free ARV drugs were sometimes not available in the health facility and they had to turn to the private market. Hence, the extent of financial burden in this review might be underestimated. Conclusion: Based on the data available, we concluded that increased accessibility of free ART should be accompanied with sustained ARV drugs supply and increased financial support for PLHIV. / published_or_final_version / Community Medicine / Master / Master of Public Health

HIV/AIDS remains one of the most pressing challenges facing South African society. South Africa has the highest number of people living with HIV as well as the highest number of people on HIV treatment globally, yet only 37% of persons eligible for treatment have access to treatment. The advent of HAART ushered in a new era in the treatment of HIV infection. HIV infection was no longer a life threatening terminal illness, HIV/AIDS became a chronic manageable disease. The full clinical benefit of HAART can only be achieved with near perfect adherence i.e. > 95%. This means taking the medication exactly as prescribed; on time, no missed doses, every day, lifelong. No other chronic medication requires such stringent adherence rates for optimal therapeutic benefit, which may mean the choice between life and death. Achieving near perfect adherence poses a serious challenge to health service providers and persons on treatment as typical adherence rates for medication prescribed over long periods are in the 50 – 75 % range. Persons on HAART live with the additional burden of drug resistance and limited treatment options if near perfect adherence rates are not achieved. The purpose of this qualitative study was to explore the factors that influence adherence to HAART. These factors may be related to the person, the health care team and system, the treatment regimen, the social and economic environment or to the effects of HIV disease. Factors may either negatively or positively influence a person’s ability to adhere optimally to their prescribed treatment. A small sample of thirteen participants were purposefully selected for this study. Data was collected using in-depth interviews which were tape recorded and transcribed for thematic analysis. The value of this study is that it may assist health care providers, persons on treatment and the health care system to better comprehend the challenges of lifelong optimal adherence to HAART. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2011.

There is an increasing number of patients failing second line highly active antiretroviral therapy (AZT, DDI and LPV/r) in South Africa, where HIV-1 subtype C predominates. Mutations at gag cleavage sites (CS) have been found to correlate with resistance mutations in protease (PR). Therefore, it is important to collect data on subtype C protease and gag sequences from patients as these mutations may affect the efficacy of protease inhibitor (PI) containing drug regimens. In this study, 30 subtype-C infected second-line failures were genotyped using the ViroSeqTM resistance genotyping kit and the gag region from these isolates were then characterised. These sequences were then compared to 30 HIV-1 subtype C infected first-line failures (PI-naïve) and subtype B, C and group M naïve sequences that were downloaded from the Los Alamos Sequence Database. Amino acid diversity at the CS was measured using Mega version 4.0. To investigate the effect of CS mutations on replication capacity, a mutation was introduced by site-directed mutagenesis (Stratagene’s QuikChange Site-Directed Mutagenesis kit). Of the 30 second-line failures that we genotyped, only 16 had resistance mutations in PR and 23 in gag. The most frequent major PI mutations were: I54V/L, M46I, V82A, and I84V and in gag CS were V390L/I and A431V. Interestingly the A431V mutation significantly correlated with protease mutations M46I/L, I54V and V82A. The virus carrying the A431V mutation in vitro was found to have a lower replication capacity compared to the wild type. These findings emphasize the need for further investigation of gag mutations and their contribution to the evolution of HIV resistance to PIs. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2010.

Sub-Saharan Africa bears 70% of the global HIV burden with KwaZulu-Natal (KZN) identified as the epicenter of this pandemic. HIV related nephropathy (HIVRN) exceeds any other causes of kidney diseases responsible for end stage renal disease, and has been increasingly recognized as a significant cause of morbidity and mortality. There is nonetheless a general lack of surveillance and reporting for HIVRN exists in this geographical region. Consequentially, the aim of this study was to outline the histopathogical spectrum of HIVRN within KZN. Moreover, from a pathology standpoint, it is important to address whether HIVRN was a direct consequence of viral infection of the renal parenchyma or is it a secondary consequence of systemic infection. Additionally, an evaluation of the efficacy of Highly Active Anti-Retroviral Therapy (HAART) in combination with angiotensin converting enzyme inhibitors (ACE-I) was performed via a genetic appraisal of localized replication of HIV-1 in the kidney, ultrastructural review and immunocytochemical expression of a podocyte maturity and proliferation marker pre and post-HAART. Blood and renal biopsies were obtained from 30 children with HIV related nephropathy pre- HAART, followed-up clinically for a period of 1 year. This cohort formed the post-HAART group. Clinical and demographic data were collated and histopathology, RT-PCR, sequencing, immunocytochemistry and transmission electron microscopy was performed. The commonest histopathological form of HIVRN in children (n = 30) in KZN was classical focal segmental glomerular sclerosis (FSGS) presented in 13(43.33%); mesangial hypercellularity 10(30%); mesangial, HIV associated nephropathy 3(11%) and minimal change disease 2(6.67%). Post-HAART (n = 9) the predominant pathology was mesangial hypercellularity 5(55.56%); FSGS 3(33.33%) and sclerosing glomerulopathy 1(11.11%). This study also provides data on the efficacy of HAART combined with ACE-I. The immunostaining pattern of synaptopodin, Ki67 and p24 within the glomerulus expressed as a mean field area percentage was significantly downregulated in the pre-HAART compared to the post-HAART group respectively (1.14 vs. 4.47%, p = 0.0068; 1.01 vs.4.68, p < 0.001; 4.5% vs 1.4%, p = 0.0035). The ultrastructural assessment of all biopsies conformed to their pathological appraisal however, features consistent with viral insult were observed. Latent HIV reservoirs were observed within the podocyte cytoplasm but was absent in mesangial or endothelial cells. Real-Time polymerase chain reaction assays provided evidence of HIV-1 within the kidney. Sequence analysis of the C2-C5 region of HIV-1 env revealed viral diversity between renal tissue to blood. In contrast to a collapsing type of FSGS that occurs in adults, the spectrum of paediatric nephropathy in treatment-naive children within KwaZulu-Natal was FSGS with mesangial hypercellularity. Additionally, our study demonstrates podocyte phenotype dysregulation pre- HAART and reconstitution post therapy. Evidence of ultrastructural viral reservoirs within epithelial cells is supported by a genetic appraisal confirming the ubiquitous presence of HIV DNA in renal tissue. Moreover, sequence analysis showed viral evolution and compartmentalization between renal viral reservoirs to blood. Finally, the interplay of viral genes and host response, influenced by genetic background, may contribute to the variable manifestations of HIV-1 infection in the kidney in our paediatric population. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.