Orientador: Helaine Maria Besteti Pires Mayer Milanez / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T14:20:51Z (GMT). No. of bitstreams: 1 PinhoNeto_OtavioSoares_D.pdf: 1689484 bytes, checksum: 9ac072f9702d3565268cb5bc1930d222 (MD5) Previous issue date: 2014 / Resumo: OBJETIVO: Analisar os protocolos de Antirretrovirais em uma coorte de gestantes HIV positivas e recém-natos expostos em seguimento no Serviço de Assistência Especializada (SAE) Familiar/Hospital Universitário Lauro Wanderley (HULW)/Universidade Federal da Paraíba (UFPB) no período de 2005 a 2012. SUJEITOS E MÉTODOS: Estudo descritivo, do tipo coorte, retrospectivo, numa abordagem quantitativa, a partir de um grupo de gestantes HIV+ e seus recém-nascidos (RN) expostos, atendidas no SAE Familiar do HULW/UFPB. Os dados foram codificados, digitados e armazenados em um banco de dados criado com esse propósito. Cada par mãe-RN foi identificado com um número. Foi realizada uma análise descritiva das características sociodemográficas da gestante, do acompanhamento pré-natal, do uso de terapia antirretroviral (TARV), do parto e do recém-nascido, através de distribuição percentual ou média. Posteriormente, foi realizada a análise das classes dos antirretrovirais e seus desfechos para a mãe e recém-nascidos expostos. As possíveis associações entre as variáveis categóricas foram testadas através do teste t (dados paramétricos). Não foi possível a realização de análise multivariada devido ao pequeno número de crianças infectadas. RESULTADOS: A taxa de transmissão vertical (TV) no SAE Familiar HULW/UFPB entre 2005 e 2012 foi de 3,9% em uma coorte de 153 gestações analisadas. A média de idade das gestantes foi de 25 anos e a de escolaridade de 7 anos. A maioria era de mulheres negras (78,7%), com união estável (59%), e a principal categoria de exposição foi a sexual (96,5%). Mais de cinquenta por cento já apresentavam diagnóstico do HIV anterior à gravidez estando 41% em uso de TARV. A média de CD4 inicial foi de 440 células/ml e, após uso de TARV de 516,07 células/ml. A média de carga viral (CV) pré uso de TARV foi de 24.022. Mais de 70% apresentaram carga viral indetectável com 34 semanas de gestação. Usaram TARV com IP 92% e 8% um esquema com nevirapina. Não foi utilizada monoterapia com AZT nessa coorte. A média de idade gestacional no parto foi de 36 semanas e em 95% dos casos a via de parto foi cesárea. A grande maioria dos casos (98%) recebeu AZT endovenoso no parto. O peso médio dos recém-nascidos foi de 2,89 gramas e apenas 17,64% tiveram baixo peso. A presença de prematuridade, patologias neonatais e o não uso do AZT intraparto foram fatores que se associaram a um maior risco de transmissão vertical. Não foi possível a realização de análise multivariada devido ao pequeno número de crianças infectadas. Houve poucos efeitos colaterais associados ao uso da TARV na gestação, sendo o mais frequente a presença de anemia materna (58,4%) e de anemia neonatal (21,6%). Não se observaram efeitos adversos graves, tanto na mãe quanto no recém-nascido. CONCLUSÃO: A taxa de TV no serviço universitário de João Pessoa foi de 3,9%, principalmente associada à prematuridade, patologia neonatal e não uso do AZT venoso intraparto. Houve baixa ocorrência de efeitos adversos, sendo mais frequente a anemia, tanto na mãe quanto no recém-nascido / Abstract: OBJECTIVE: To analyze antiretroviral therapy protocols in a cohort of HIV-positive pregnant women and exposed newborns followed at Serviço de Assistência Especializada (SAE) Familiar / Hospital Universitário Lauro Wanderley (HULW), Universidade Federal da Paraíba (UFPB), from 2005 to 2012. SUBJECTS AND METHODS: Descriptive, retrospective cohort study, using a quantitative approach, conducted on a group of HIV-positive pregnant women and their exposed newborns followed at SAE/HULW. Data were codified, entered and stored in a database created specifically for this purpose. Each mother-child pair was identified by a number. A descriptive analysis of the sociodemographic characteristics of pregnant women, prenatal care, use of antiretroviral therapy (ART), and delivery and neonate parameters was conducted using percentages or means. An analysis of the classes of antiretroviral drugs and their associated outcomes for mothers and exposed newborns was then conducted. Potential associations between categorical variables were assessed with the t-test (parametric data). Multivariate analysis could not be performed due to the small number of children infected. RESULTS: The mother-to-child transmission rate at SAE/HULW-UFPB between 2005 and 2012 was 3.9%, in a cohort of 153 pregnancies. The mean patient age was 25 years and the mean educational attainment was 7 years of schooling. Most subjects were black women (78.7%), in a stable relationship (59%), and the main risk factor was sexual contact (96.5%). More than 50% already had a diagnosis of HIV infection prior to pregnancy, and 41% were on ART. The mean CD4 count was 440 cells/ml at baseline and 516.07 cells/ml after ART. The median viral load before ART was 24.022. Over 70% had an undetectable viral load at 34 weeks of gestation. Overall, 92% were on PI-containing ART regimens and 8% were on nevirapine-containing regimens. AZT monotherapy was not used in this cohort. The mean gestational age at delivery was 36 weeks, and in 95% of cases, the mode of delivery was cesarean. The vast majority of cases (98%) received intrapartum intravenous AZT. The average birth weight of newborns was 2,890 g, and only 17.6% were underweight. Presence of prematurity, neonatal morbidity, and failure to administer intrapartum AZT were factors associated with higher risk of vertical transmission. Multivariate analysis could not be performed due to the small number of infected children. There was a low incidence of side effects associated with ART during pregnancy, the most common being maternal anemia (58.4%) and neonatal anemia (21.6%). No serious adverse effects were observed in either mothers or newborns. CONCLUSION: The rate of mother-to-child transmission at this university-based facility in João Pessoa was 3.9%, and was mainly associated with prematurity, neonatal morbidity, and failure to administer intrapartum intravenous AZT. There was a low rate of adverse effects, the most common being anemia, in both mothers and newborns / Doutorado / Saúde Materna e Perinatal / Doutor em Ciências da Saúde

Few studies have assessed the optimum second line highly active anti-retroviral therapy (HAART) regimen in patients who had failed on the first-line HAART in resource-limited settings. This study aimed to compare the Protease inhibitor (PI)-based second line HAART regimens used in one clinic in Trinidad by comparing immunological, virological and clinical outcomes of patients on the different second line HAART regimens. The records of 35 treatment-experienced patients, over 21years of age and on PI-based regimens for at least six months, were analysed using SPSS version 20. The regimen containing TDF/FTC/AZT/LPV/r proved to produce superior outcomes compared to the other second line regimens. Due the small number of usable patients’ records, the findings cannot be generalised but indicate directions for future studies attempting to compare the treatment outcomes of different second line HAART regimens / Health Studies / M. A. (Public Health)

Submitted in fulfillment of the requirements for the Degree of Master of Technology: Biomedical Technology, Durban University of Technology, 2012. / Antiretroviral therapy (ART) was introduced because it has shown to reverse the Acquired Immunodeficiency syndrome (AIDS), by reducing the HIV replication, allowing the regeneration of the patient’s immune system. ART is given to patients for the rest of their lives as part of HIV clinical care, but the use of ART has shown evidence of metabolic side effects which range from manageable to life threatening complications. Aims and objectives of the study The aim of the study was to investigate whether patients on ART developed metabolic side effects such as pancreatitis, dyslipidaemia and hepatotoxicity. These metabolic side effects were determined by laboratory testing of blood levels of specific biomarkers at stipulated intervals. Any significant change in the blood levels of these specific biomarkers was identified. Methodology : The study included 92 patients who were already selected for the ART programme which is in accordance to the South African National Antiretroviral Therapy Guidelines of 2003 Laboratory blood analysis was conducted. The repeated measures analysis of variance (ANOVA) was used to compare changes in biomarkers over time. The severity of each side effect was assessed by grading each biomarker laboratory result through the use of an established toxicity grading table. Results : It was found that the biomarker blood levels were not significantly altered within 12 months of ART, however, there was a gradual increase of most biomarker values, indicating that abnormalities may be detected after a longer period of treatment. Conclusion : Within 12 months of treatment, life-threatening toxicities were not detected. It may be speculated that if ART is monitored correctly, life-threatening toxicities may be avoided in many patients.

The Human immunodeficiency virus (HIV) pandemic has resulted in a heavy global disease burden, and clinically causes Acquired Immuno-Deficiency Syndrome (AIDS). The development of highly active antiretroviral therapy (HAART) has achieved remarkable control of the rapidly evolving HIV. However, HIV remains neither curable nor preventable by vaccine, and in the developing regions worst affected by HIV, HAART remains inaccessible to most patients. Furthermore, the change in both immunology and viral evolution during chronic HIV infection and its relation to AIDS pathogenesis remains unknown. Following the failure of recent HIV vaccines, it is believed that a better understanding of host-pathogen interaction is vital to advance therapeutic (vaccine and drug) design. In this thesis, I have performed an investigation of viral adaptation in response to different selection forces during advanced HIV infection and AIDS. The thesis first examined a case study that reveals the potential role of B cell-mediated neutralising antibody (NAb) in chronic HIV infection through the unexpected effect of B cell depletion agent, anti-CD20 (Rituximab). Here, longitudinal results have shown that viral load (VL), env gene diversity, and NAb sensitive strains increased during B cell and NAb depletion as a result of Rituximab administration, and reversed as B cells recovered. The study provides preliminary evidence to support the idea that NAb may be effective at suppressing HIV. The rest of the thesis focused on the cross-sectional cohort at Bloemfontein, South Africa (n=1491), a resource-limited region affected by the pandemic. Here, we used methods that include molecular and pretherapy drug resistance epidemiology, mathematical modelling, phylogenetically adjusted bioinformatics analysis and in vitro viral replication capacity (VRC) assay to study materials including cohort demography, plasma samples, CD4 cell count, VL, viral genetic sequences and host human leukocyte antigen (HLA) tissue types. Our analysis was further augmented by the additional data kindly contributed by our neighbouring Durban cohort collaborators (n=775), which also includes an IFN! ELISPOT assay that measures cytotoxic T lymphocyte (CTL) responses. Using the HIV pol sequencing data and phylogenetic analysis we confirmed that the local molecular epidemiology is similar to the circulating strains documented in the regional database. However, the pretherapy drug resistance mutation screening results have revealed an unexpected high incidence of drug-induced viral mutants in the AIDS patients with CD4 counts <100 cells/μl. According to mathematical modelling, this finding is attributable to additional sources of antiretroviral therapy exposure, which warrants public health caution. The investigation then focused on studying the changes in HLA class I mediated CTL selection and viral evolution as CD4 counts are reduced in AIDS. Interestingly we have noted evidence that suggest weakening CTL immune selection against gag during AIDS is associated with increased viral fitness (measured by VRC) and reversion of previous immune-escape mutations which conferred high fitness costs. In conclusion, this thesis compared different sources of host and drug mediated HIV selection and its implication for viral evolution. The identification of more bottleneck sites conferring high fitness costs to the selection of escape mutants is expected to be helpful in the design of future therapeutics (via vaccine, drug, immune therapy, or public health strategy). As we have learnt from the principle of combinational ARV, it would be desirable for a vaccine to select HIV at multiple sites of high escape-mutation fitness cost, hence offering protective effect.

Introducción: La atención farmacéutica mejora la adherencia del paciente al tratamiento, por lo que es necesario que el farmacéutico cuente con instrumentos para evaluarla y mejorarla mediante su intervención en el seguimiento farmacoterapéutico (SFT). Objetivos: Evaluar el impacto de la intervención farmacéutica en la mejora de la adherencia de los pacientes con virus de la inmunodefi ciencia humana (VIH) y sida, e identifi car los factores que infl uyen en ella y que pueden ser modifi cados por la intervención farmacéutica en el SFT. Métodos: Se realizó SFT durante 23 meses a 52 pacientes mayores de 18 años de edad, con tratamiento antirretroviral durante más de 3 meses, que dieron su consentimiento informado. La adherencia se evaluó con el CEAT-VIH (cuestionario para evaluar la adhesión al tratamiento antirretroviral) al inicio y al fi nal de 6 meses de SFT. Resultados: La puntuación total del CEAT-VIH (p <0,05; intervalo de confi anza del 95%), el cumplimiento del tratamiento (p <0,001) y la percepción del paciente respecto a su enfermedad y tratamiento antirretroviral (p <0,001) incrementaron signifi cativamente su valor. La educación al paciente para incrementar la adherencia al tratamiento (46%) fue la intervención farmacéutica más frecuente. Conclusiones: Se demuestra que la intervención del farmacéutico, mediante el SFT, mejora la adherencia al tratamiento antirretroviral. El farmacéutico mejoró los aspectos de cumplimiento y percepción del paciente sobre su tratamiento y enfermedad. Los farmacéuticos pueden utilizar el CEAT-VIH como instrumento para evaluar la adherencia en la práctica del SFT. / Introduction: Pharmaceutical care improves medication adherence that is why is important that the pharmacist uses instruments to evaluate and improves it through pharmaceutical intervention at pharmaceutical care. Objective: To evaluate the impact of the pharmaceutical intervention in the improvement of the medication adherence of the patients with HIV and AIDS, and to identify the factors that infl uence on medication adherence and which one could be modifi ed by the pharmaceutical intervention during pharmaceutical care. Methods: Pharmacotherapeutic follow-up was realized for 23 months to 52 patients, older than 18 years, with antiretroviral treatment for up to three months, consent informed was obtained from patients. Medication adherence was evaluated with CEAT-HIV (questionnaire to evaluate the adhesion to the antiretroviral treatment) at the beginning and at the end of the study (6 months). Results: The fi nal score from CEAT-HIV (p <0.05; 95% IC), treatment compliance (p <0.001) and patient’s beliefs to the disease and antiretroviral treatment (p <0.001) improved signifi cantly with the pharmaceutical intervention. The more frequent pharmaceutical intervention was education to the patient to increment the adherence to the treatment (46%). Conclusion: These results demonstrate that the pharmacists’ intervention through pharmacotherapeutic follow-up improves the adherence to the antiretroviral treatment. The pharmacist was able to improve aspects of compliance and patient’s beliefs about the treatment and disease. The pharmacist could utilize CEAT-VIH as an instrument to evaluate the adherence in HIV/AIDS patients.

Thesis (MPH.) --University of Limpopo, 2018 / Background: The prevalence of HIV in South Africa has increased largely due to the combined effect of new infections, and a successfully expanded antiretroviral treatment programme, which has increased survival among people living with HIV. As the up-scaling of patients on ART has been increased, the aim of the current study was to investigate the variations of the clinical outcomes between patients initiated with CD4 < 350 and of those above 350 after the implementation of the new eligibility criteria for ARV therapy. Methods The current study used quantitative approach to retrospectively review a total of 488 records of adult patient who were registered in health facilities which were purposefully sampled from Sekhukhune District of Limpopo Province. SPSS version 23.0 was used to analyse data. Results Approximately 60% of the patients initiated on ART were having CD4 count <350 and male patients were more at 74% as compared to females at 54.7%. Patients who started ART with a baseline CD4 >350 had a high rate of lost to follow up within 3 months after start of ART at 15% than those with a baseline CD4 <350 at 10.2. More patients were lost to follow-up shortly after starting treatment at 3 months at an average of 13.8% in both CD4 counts. Majority of patients retained in care were those who started ART treatment with a baseline CD4<350 at 87.4%. Viral load completion rate at 12 months was higher than that of 6 months, at 86.8 and 80.5 respectively. Patients with a baseline CD4 >350 suppressed more than those who started ART with a baseline CD4 <350 at both 6 and 12 months at >90% suppression rate. Lastly, most of the patients died within 3 months of ART treatment and had a baseline CD4 < 350 than at 2.4% those with a baseline CD4 >350 at 0.6%. Conclusions The implementation of the new eligibility criteria of ART initiation improves the clinical outcome of patients on ART. There are still patients that are missed to be monitored viral load bloods which play a key role in determining the clinical outcomes of patients. Clinicians and nurses should adhere to the recommended time frames for monitoring of ART patients to improve clinical outcomes. Keywords: HIV/AIDS, antiretroviral therapy, clinical outcome, ART initiation; Eligibility Criteria;

Measles remains a major global public health problem. Attainment of high population immunity to measles through vaccination is necessary to control this disease. Children infected with HIV infection often experience secondary measles vaccine failure by 2 years of age, making them susceptible to measles. It is not clear whether HIV-infected children on Highly Active Antiretroviral Treatment (HAART), older than 2 years, have a higher risk of measles than HIV-uninfected children. This retrospective cohort study, guided by the proximate determinants framework, was conducted to compare the risk of measles between HIV-infected children on HAART (exposed) and HIV-uninfected peers (unexposed). The age group with the highest measles susceptibility in the exposed children, which could inform timing for revaccination, was investigated. The role of age at initiation of HAART, low CD4+ count, and undernutrition as predictors of the risk of measles in the exposed children was examined. Univariate, bivariate, and binomial logistic regression analytical procedures were used in data analysis. Results showed no significant difference in the risk of measles between exposed and unexposed children. The age groups 5 to 9 years and 2 to 4 years were the first and second most affected by measles among the exposed children. Undernutrition (stunting) was a significant predictor of measles in exposed children (odds ratio of 4.14, p = 0.02), while age at initiation of HAART and CD4+ count prior to measles exposure were not. The study findings provide evidence to inform vaccination policy and nutrition care for HIV-infected children on HAART in Uganda, so as to reduce their risk of measles illness and mortality, thus contributing to positive social change for the children and the country.

The current study aims to determine physical activity levels among people living with HIV treated with high active antiretroviral therapy in Kigali, Rwanda. A cross-sectional design using quantitative method was used. The participant’s levels of physical activity participation and their association with anthropometric profiles were measured, using a structured selfadministered questionnaire adapted from the Sub-Saharan Africa Activity Questionnaire. Based on a scientific calculation, 407 clients passing through the clinics were included in the study. A convenient sample of people attending the clinics approached to participate voluntarily in the study. The findings of the current study highlighted the lack of motivation, lack of time and fear of worsening the disease amongst the strong barriers to physical activity participation. The current study recommends education about the benefits of physical activity participation and encouragement of patient treated with high active antiretroviral therapy in Rwanda to be emphasized on to improve their lives.

The current study aims to determine physical activity levels among people living with HIV treated with high active antiretroviral therapy in Kigali, Rwanda. A cross-sectional design using quantitative method was used. The participant’s levels of physical activity participation and their association with anthropometric profiles were measured, using a structured selfadministered questionnaire adapted from the Sub-Saharan Africa Activity Questionnaire. Based on a scientific calculation, 407 clients passing through the clinics were included in the study. A convenient sample of people attending the clinics approached to participate voluntarily in the study. The findings of the current study highlighted the lack of motivation, lack of time and fear of worsening the disease amongst the strong barriers to physical activity participation. The current study recommends education about the benefits of physical activity participation and encouragement of patient treated with high active antiretroviral therapy in Rwanda to be emphasized on to improve their lives.

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