Modelling HIV/AIDS length of stay in Portugal

Tese apresentada como requisito parcial para obtenção do grau de Doutor em Estatística e Gestão de Informação pelo Instituto Superior de Estatística e Gestão de Informação da Universidade Nova de Lisboa

Bull's Eye Maculopathy in a Patient Treated with Efavirenz

Objective: To report a case of retinal toxicity associated with efavirenz in an adult. Methods: We describe a case of gradual-onset blurry vision in both eyes in a 37-year-old HIV Caucasian woman, on antiretroviral therapy (ART), including efavirenz. Results: The patient presented with a best corrected visual acuity of 20/100 for the right eye (RE) and 20/125 for the left eye (LE). Fundoscopy revealed mottled atrophic changes of the macular retinal pigment epithelium (RPE) in both eyes. Fluorescein angiography revealed an annular pattern of RPE atrophy in both eyes. Full-field electretinography (ERG) was normal. Conclusions: Based on our patient’s history and on previous reports, efavirenz seems to be the culprit in this case. Our report provides evidence in support of routine ophthalmological evaluation of patients on efavirenz.

Collapsing Glomerulopathy. A Treatable Disease?

Renal disease is a relatively common complication in human immunodeficiency virus (HIV) infected patients and has become the fourth leading cause of death in AIDS individuals, immediately following septicaemia, pneumonia and hepatic disease. HIV associated nephropathy, HIV associated immune complex renal disease and HIV associated thrombotic microangiopathy are the main causes of chronic renal failure in this population. The authors report a case of a 44 year-old black male, HIV 1 infected with low CD4 count, admitted to the nephrology department with non nephrotic proteinuria and renal failure. Renal biopsy revealed a focal segmental glomerulosclerosis collapsing variant. The patient was treated with highly active antiretroviral therapy and an ACE inhibitor and, at 3 months of follow-up, has recovered his renal function. This case illustrates the efficacy of highly active antiretroviral therapy (HAART) on HIV associated nephropathy. Prospective studies are needed to evaluate HAART in the treatment of HIV associated nephropathies.

Renal Transplantation in HIV-Infected Patients: The First Portuguese Review

INTRODUCTION: With the introduction of combination antiretroviral therapy (cART), prognosis of human immunodeficiency virus (HIV) infection has been improved and kidney transplantation (KT) in HIV-positive patients became possible. METHODS: We reviewed the demographic, clinical, laboratory, and therapeutic data of all the HIV-infected patients who underwent KT between 2009 (first KT in Portugal in a HIV-infected patient) and May 2014. Case accrual was through all Portuguese KT centers where a KT in an HIV-infected patient was performed. Patients were transplanted following the American and Spanish guideline recommendations that included maintenance on cART, undetectable plasma HIV RNA copies, and absolute CD4 counts of ≥ 200 cells/μL in the last 6 months. RESULTS: Fourteen KT were performed on men and 3 on women. The mean age of patients at the time of transplantation was 49.9 ± 11.7 years. HIV status was known for 12 ± 5 years. Eight patients had AIDS in the past and all patients received grafts from deceased donors. Twelve patients (64.7%) underwent induction therapy with basiliximab and 2 patients experienced early graft loss. In 2 patients, humoral rejection was diagnosed and in 3 patients, cellular rejection. Two patients died and an additional patient had early graft loss. CONCLUSION: KT is a possible, but challenging, renal replacement therapy in selected HIV-positive patients. Even in those with AIDS criteria in the past, when the disease is controlled, and after the reconstitution of the immune system with cART, KT can be performed. Nevertheless, the risk-benefit ratio for each patient needs to be taken in consideration.

Economic analysis in health care regulation : three essays

ABSTRACT - It is the purpose of the present thesis to emphasize, through a series of examples, the need and value of appropriate pre-analysis of the impact of health care regulation. Specifically, the thesis presents three papers on the theme of regulation in different aspects of health care provision and financing. The first two consist of economic analyses of the impact of health care regulation and the third comprises the creation of an instrument for supporting economic analysis of health care regulation, namely in the field of evaluation of health care programs. The first paper develops a model of health plan competition and pricing in order to understand the dynamics of health plan entry and exit in the presence of switching costs and alternative health premium payment systems. We build an explicit model of death spirals, in which profitmaximizing competing health plans find it optimal to adopt a pattern of increasing relative prices culminating in health plan exit. We find the steady-state numerical solution for the price sequence and the plan’s optimal length of life through simulation and do some comparative statics. This allows us to show that using risk adjusted premiums and imposing price floors are effective at reducing death spirals and switching costs, while having employees pay a fixed share of the premium enhances death spirals and increases switching costs. Price regulation of pharmaceuticals is one of the cost control measures adopted by the Portuguese government, as in many European countries. When such regulation decreases the products’ real price over time, it may create an incentive for product turnover. Using panel data for the period of 1997 through 2003 on drug packages sold in Portuguese pharmacies, the second paper addresses the question of whether price control policies create an incentive for product withdrawal. Our work builds the product survival literature by accounting for unobservable product characteristics and heterogeneity among consumers when constructing quality, price control and competition indexes. These indexes are then used as covariates in a Cox proportional hazard model. We find that, indeed, price control measures increase the probability of exit, and that such effect is not verified in OTC market where no such price regulation measures exist. We also find quality to have a significant positive impact on product survival. In the third paper, we develop a microsimulation discrete events model (MSDEM) for costeffectiveness analysis of Human Immunodeficiency Virus treatment, simulating individual paths from antiretroviral therapy (ART) initiation to death. Four driving forces determine the course of events: CD4+ cell count, viral load resistance and adherence. A novel feature of the model with respect to the previous MSDEMs is that distributions of time to event depend on individuals’ characteristics and past history. Time to event was modeled using parametric survival analysis. Events modeled include: viral suppression, regimen switch due virological failure, regimen switch due to other reasons, resistance development, hospitalization, AIDS events, and death. Disease progression is structured according to therapy lines and the model is parameterized with cohort Portuguese observational data. An application of the model is presented comparing the cost-effectiveness ART initiation with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus one non-nucleoside reverse transcriptase inhibitor(NNRTI) to two NRTI plus boosted protease inhibitor (PI/r) in HIV- 1 infected individuals. We find 2NRTI+NNRTI to be a dominant strategy. Results predicted by the model reproduce those of the data used for parameterization and are in line with those published in the literature.

Do anti-retroviral treatments encourage individuals to get tested for HIV/AIDS in Sub-Saharan Africa?

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA – School of Business and Economics

Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Paradoxical reaction to the treatment of tuberculosis uncovering previously silent meningeal disease

The development of paradoxical clinical worsening following initiation of tuberculosis treatment may complicate the clinical course of both HIV-infected and uninfected patients. We report a severe manifestation of the so called paradoxical reaction to the treatment of tuberculosis that unmasked previously silent meningeal disease in a 34-year-old HIV-infected male patient.

Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis C virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin

Comorbidities in human immunodeficiency virus infection are of great interest due to their association with unfavorable outcomes and failure of antiretroviral therapy. This study evaluated the prevalence of coinfection by human immunodeficiency virus and viral hepatitis in an endemic area for hepatitis B in the Western Amazon basin. Serological markers for hepatitis B virus, hepatitis C virus and hepatitis D virus were tested in a consecutive sample of all patients referred for treatment of human immunodeficiency virus or acquired immunodeficiency syndrome. The variables sex, age, origin and exposure category were obtained from medical records and from the sexually transmitted diseases and acquired immunodeficiency syndrome surveillance database. Among 704 subjects, the prevalence of chronic hepatitis B carriage was 6.4% and past infection 40.2%. The presence of hepatitis B was associated with birth in hyperendemic areas of the Amazon basin, male sex and illegal drug use. The overall prevalence of hepatitis C was 5% and was associated with illegal drug use. The prevalence of hepatitis B and C among human immunodeficiency virus or acquired immunodeficiency syndrome patients in the Western Amazon basin was lower than seen elsewhere and is probably associated with the local epidemiology of these viruses and the degree of overlap of their shared risk factors. An opportunity presents itself to evaluate the prevention of hepatitis C through harm reduction policies and hepatitis B through vaccination programs among human immunodeficiency virus or acquired immunodeficiency syndrome patients.

Oral cavity lymphoma as secondary AIDS-defining neoplasm in a patient on HAART with immune reconstitution

Lymphomas of the oral cavity are a rare complication of advanced HIV/AIDS disease. The clinical appearance of these neoplasms includes masses or ulcerative lesions that involve the oral soft tissue and the jaw as the predominant manifestation. We report the case of a patient with AIDS who developed diffuse large B-cell non-Hodgkin’s lymphoma of the oral cavity during highly active antiretroviral therapy, with undetectable plasma viral load and immune reconstitution.

Tuberculosis incidence and risk factors among patients living with HIV/AIDS in public health service institutions in Brasilia, Federal District

In order to estimate the incidence of and risk factors for developing tuberculosis, the clinical charts of a retrospective cohort of 281 HIV-positive adults, who were notified to the AIDS Program of the Health Department of Brasilia in 1998, were reviewed in 2003. All the patients were treatment-naive regarding antiretroviral therapy at the time of inclusion in the cohort. Twenty-nine patients were identified as having tuberculosis at the start of the study. Thirteen incident tuberculosis cases were identified during the 60 months of follow-up, with an incidence density rate of 1.24/100 person-years. Tuberculosis incidence was highest among patients with baseline CD4+ T-lymphocyte counts < 200 cells/µl who were not using antiretroviral therapy (incidence = 5.47; 95% CI = 2.73 to 10.94). Multivariate analysis showed that baseline CD4+ T-lymphocyte counts < 200 cells/µl (adjusted hazard ratio [AHR] = 5.09; 95% CI = 1.27 to 20.37; p = 0.02) and non-use of antiretroviral therapy (AHR = 12.17; 95% CI = 2.6 to 56.90; p = 0.001) were independently associated with increased risk of tuberculosis.

Pre-travel health advice for human immunodeficiency virus-infected travelers, from Rio de Janeiro

Counseling for human immunodeficiency virus infected travelers is becoming increasingly specialized. Previous studies have reported the experience of HIV-infected travelers from temperate-climate countries but little is known about HIV-infected travelers from tropical countries. A retrospective study was conducted on HIV-infected travelers presenting at a travel health clinic in Rio de Janeiro. Eleven journeys by ten people were recorded. Brazil (Amazon region and Northeast) was the destination for six journeys. Other destinations were Peru, Angola, Europe and Asia. Nine attendees were undergoing antiretroviral therapy. Few HIV-infected people from Rio de Janeiro consulted a travel medicine specialist before traveling. Since they travel to destinations in Brazil and abroad where there are endemic diseases not encountered in Rio de Janeiro, careful pre-travel planning needs to be undertaken. Strategies for increasing the frequency of pre-travel consultations need to be developed, such as closer collaboration between HIV clinics and travel health clinics.

Progressive multifocal leukoencephalopathy as an AIDS-defining condition in a patient with high CD4+ T-lymphocyte count

We present the case of a 31-year-old man with acute manifestation of progressive multifocal leukoencephalopathy (PML) as an AIDS-defining disease. The patient presented with a three-day history of neurological disease, brain lesions without mass effect or contrast uptake and a slightly increased protein concentration in cerebrospinal fluid. A serological test for HIV was positive and the CD4+ T-cell count was 427/mm³. Histological examination of the brain tissue revealed abnormalities compatible with PML. The disease progressed despite antiretroviral therapy, and the patient died three months later. PML remains an important cause of morbidity and mortality among HIV-infected patients.

Fatores que influenciam a adesão à terapêutica antirretroviral : a perceção dos enfermeiros de um serviço de infeciologia

RESUMO - A investigação no âmbito da infeção por VIH/SIDA tem tido avanços notáveis, nomeadamente no que se refere à evolução da terapêutica antirretroviral, sendo atualmente o único meio de controlar a doença. Nesta área, a compreensão da problemática da adesão torna-se importante para as instituições e para os profissionais de saúde, quer pelas taxas de morbilidade e mortalidade associadas à doença, quer pelos problemas de saúde pública e pelos gastos financeiros das organizações de saúde. A adesão ao regime terapêutico é um conceito que engloba tanto o cumprimento da prescrição medicamentosa, como dos comportamentos promotores de saúde. O presente estudo teve como objetivo identificar como os enfermeiros, a desempenhar funções num serviço de infeciologia, percecionam a adesão à terapêutica antirretroviral, por indivíduos portadores de VIH/SIDA. Participaram neste estudo nove enfermeiras a desempenhar funções no serviço de Medicina 1/Infeciologia/HDI do Hospital Fernando Fonseca, EPE, que reuniam os critérios definidos. Como metodologia para a identificação da perceção dos enfermeiros realizou-se um estudo qualitativo e utilizou-se uma entrevista semi-estruturada. Da análise das entrevistas, resultaram diferentes áreas temáticas. Os resultados obtidos evidenciam a importância atribuída à adesão à terapêutica antirretroviral e demostram que o acompanhamento dos doentes pelos profissionais e instituições de saúde permite o desenvolvimento de estratégias promotoras de adesão. Verifica-se que é ainda necessário percorrer um longo caminho, de forma a se obterem resultados ótimos de adesão. Contudo, os resultados obtidos no presente estudo são um incentivo para o desenvolvimento de estratégias de adesão e para a melhoria da gestão da qualidade.

Evaluation of laboratory markers of progression of HIV disease to death

INTRODUCTION: One of the important current problems in HIV/AIDS infection is the establishment of epidemiological and laboratorial prognostic parameters during patient follow-up. This study aimed at analyzing the evolution of laboratory tests: CD4 lymphocyte count, viral load, hemoglobin (Hb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the epidemiological variables sex and age as prognostic factors for survival in progression to death among AIDS patients. METHODS: A retrospective study was conducted using analysis of medical records, and prospective 24-month follow-up of patients with HIV/ AIDS attended at the President Vargas Hospital Outpatient Clinic, a reference center in HIV/ AIDS attendance in the State of Maranhão, Brazil. The study analyzed patients aged 10 to 60 years old, who manifested AIDS and who were not using antiretroviral therapy or had used it for less than 5 years. The Chi-square test was used for statistical analysis. RESULTS: The sample included 100 patients - 57 were current outpatients, and 43 had died. The variables viral load (p=0.726), ALT (p=0.314), sex (p=0.687), and age (p=0.742) were analyzed, and no evidence of association between them and worst prognosis was observed. CONCLUSIONS: A significant relation was verified between low Hb levels (p=0.000) and CD4 (p=0.000) and shorter survival.