Introdução: A melhora na sobrevida de pacientes com AIDS está associada ao aumento da disponibilidade de terapia antirretroviral cada vez mais eficaz. A eficácia do tratamento exige que a adesão aos antirretrovirais seja igual ou superior a 95% das doses prescritas. Objetivo: Comparar a adesão dos pacientes durante sua participação em ensaio clínico e após esse período. Método: Estudo de coorte. Incluíram-se pacientes já inseridos em um ensaio clínico randomizado. A adesão foi aferida durante a participação no ensaio clínico, através de auto-relato. Após o encerramento do ensaio clínico, a adesão foi aferida pelo registro da retirada dos medicamentos no SICLOM. Considerou-se aderente pacientes que obtiveram escore de 95% ou mais. Resultados: Foram incluídos 310 pacientes. Maioria homens (63,2%) com idade média de 40 (±9,8) anos. O regime terapêutico mais utilizado por 52,9% dos pacientes foi associação de zidovudina + lamivudina com efavirenz. A taxa de adesão foi de 60,8% durante a participação no ensaio clínico e de 35,2% no segundo momento (P<0,001). O escore médio considerando a adesão média do período aferida por auto-relato foi maior (M=88,9% DP 19,2) que a obtida a partir do registro das retiradas dos antirretrovirais no SICLOM (M=78,1% ±DP 28,5; P=0,02). Conclusão: A adesão dos pacientes durante a participação no ensaio clínico foi melhor do que no período após o término deste. A adesão não foi satisfatória em ambos os períodos alertando para necessidade de intervenções continuadas para melhorar a adesão à terapia antirretroviral. / Background: The improvement in survival of AIDS patients is associated with increased availability of antiretroviral therapy more effective. The effective treatment requires regimen adherence at least of 95% of the prescribed doses. Objective: To compare the adherence of patients during their participation in clinical trial and thereafter. Method: Cohort study. It included patients already entered into a clinical trial. Adherence was measured during participation in the trial through self-report. After the end of the Clinical trial, the adherence was measured by recording the pharmacy refill of medication in SICLOM. It was considered adherent patients achieving a score of 95% or more. Results: We included 310 patients. Most men (63.2%) aged average 40 (± 9.8) years. The most widely used regimen for 52.9% of patients was the association of zidovudine + lamivudine with efavirenz. The rate of compliance was 60.8% during participation in the trial and 35.2% in second time (P <0.001). The average score given the accession mean period measured by self-report was higher (M = 88.9% SD 19.2) that obtained From the record of withdrawals of antiretroviral drugs in SICLOM (M ± SD = 78.1% 28.5, P = 0.02). Conclusion: The patient compliance during participation in clinical trial was better than in the period after the end of it. The membership does not was satisfactory in both periods need for warning continued interventions to improve adherence to antiretroviral therapy.

Introdução: Uma proporção significante de pacientes infectados por HIV-1 (pacientes HIV-1+) tratados com inibidores de protease (IPs) desenvolve mutações de resistência. Estudos recentes têm mostrado que células T CD8+ de pacientes HIV- 1+ reconhecem epitopos de Pol incluindo mutações selecionadas por drogas. Nenhum epitopo CD4+ da protease foi descrito na base de dados de Los Alamos. Objetivo: Considerando que a protease de HIV-1 é alvo de terapia antiretroviral e que essa pressão pode selecionar mutações, nós investigamos se mutações selecionadas por IPs afetariam o reconhecimento de epitopos da protease de HIV-1 por células T CD4+ em pacientes tratados com IPs. Nós investigamos o reconhecimento de três regiões da protease preditas de conter epitopos de células T CD4+ bem como mutações induzidas por IPs por células T CD4+ em pacientes HIV- 1+ tratados com IPs. Materiais e Métodos: Quarenta pacientes HIV-1+ tratados com IPs foram incluídos (30 em uso de Lopinavir/ritonavir, 9 em uso de Atazanavir/Ritonavir e 1 em uso exclusivo de Atazanavir). Para cada paciente determinou-se a seqüência endógena da protease de HIV-1, genotipagem viral e tipagem HLA classe II. Utilizamos o algoritmo TEPITOPE para selecionar peptídeos promíscuos, ligadores de múltiplas moléculas HLA-DR, codificando as três regiões da protease de HIV-1 cepa HXB2 (HXB2 4-23, 45-64, e 76-95) e 32 peptídeos adicionais contidos nas mesmas regiões incorporando as mutações induzidas por IPs mais freqüentes no Brasil. Os 35 peptídeos foram sintetizados. Respostas proliferativas de células T CD4+ e CD8+ aos peptídeos foram determinadas por ensaios de proliferação com diluição do corante CFSE. Ensaios de ligação a alelos HLA classe II foram realizados para confirmar a promiscuidade desses peptídeos e avaliar a habilidade de se ligarem a moléculas HLA presentes em cada paciente. Resultados: Todos os peptídeos foram reconhecidos por pelo menos um paciente e respostas proliferativas de células T CD4+ e CD8+ a pelo menos um peptídeo da protease de HIV-1 foram encontradas em 78% e 75% dos pacientes, respectivamente. A terceira região (Protease 76 95) foi a mais freqüentemente reconhecida. Ao compararmos as respostas de células T às seqüências da protease do HIV-1 endógeno, observamos que a maioria dos pacientes não foi capaz de reconhecer peptídeos idênticos às essas seqüências, porém reconheceram peptídeos variantes diferentes das mesmas regiões. Apenas sete pacientes responderam às seqüências endógenas. Verificamos que diversos peptídeos endógenos que não foram reconhecidos apresentaram ausência de ligação a alelos HLA portados por estes pacientes, sugerindo que mutações selecionadas por pressão imune tenham levado ao escape de apresentação de antígeno e evasão de resposta de linfócitos T CD4+. Alternativamente, isso poderia ser explicado pela presença de um vírus replicante distinto presente no plasma uma vez que somente foram obtidas seqüências provirais. Conclusão: Epitopos selvagens e mutantes da protease do HIV-1 reconhecidos por células T CD4+ foram identificados. Também verificamos que a maior parte dos pacientes não reconheceu as seqüências da protease endógena enquanto que reconheceram seqüências variantes. O reconhecimento de seqüências não-endógenas poderia ser hipoteticamente conseqüência de alvo de populações HIV-1 minoritárias; protease de HERV que contém regiões de similaridade com a protease do HIV-1; ou seqüências de HIV-1 presentes apenas em parceiros virêmicos. A falha de reconhecimento de seqüências endógenas seria mais provável devido ao escape imune, do que ao nível de apresentação ou reconhecimento por células T. Isso implica em uma conseqüência patofisiológica na evasão de respostas de células T contra a protease de HIV-1 e no fato de ser tradicionalmente considerada uma proteína pouco antigênica / Introduction: A significant proportion of protease inhibitor (PI)-treated HIV-1 infected (HIV-1+) patients develop resistance mutations. Recent studies have shown that CD8+ T cells from HIV-1 patients can recognize antiretroviral drug-induced mutant Pol epitopes. No HIV-1 protease CD4 epitopes are described in the Los Alamos database. Aims: Given that the protease of HIV-1 is a target of antiretroviral therapy and this pressure may lead to the selection of mutations, we investigated whether PI-induced mutations affect the recognition of HIV-1 protease epitopes by CD4 + T cells in PI-treated patients. We investigated the recognition of three protease regions predicted to harbor CD4+ T cell epitopes as well as PI-induced mutations by CD4+ T cells of PI-treated HIV-1+ patients. Methods: Forty PI-treated HIV-1+ patients were included (30 undergoing Lopinavir/ritonavir, 9 undergoing Atazanavir/ritonavir and 1 undergoing exclusively Atazanavir treatment). For each patients, the endogenous HIV-1 protease sequence, viral genotype and HLA class II typing were determined. We used the TEPITOPE algorithm to select promiscuous, multiple HLA-DR-binding peptides encoding 3 regions of HIV-1 HXB2 strain protease (HXB2 4-23, 45-64, and 76-95) and 32 additional peptides contained in the same regions, but encompassing the most frequent PI-induced mutations in Brazil. The 35 peptides were thus synthesized. Proliferative responses of CD4+ and CD8+ T cells against peptides were determined by the CFSE dilution assay. HLA class II binding assays were made to confirm the promiscuity of these peptides and evaluate their ability to bind the HLA molecules carried by each patient. Results: All tested peptides were recognized by at least one patient and proliferative responses of CD4+ and CD8+ T cells against at least one HIV-1 protease peptide were found in 78% and 75% patients, respectively. The third region (Protease 76-95) was the most frequently recognized. By comparing T-cell responses to HIV-1 endogenous protease sequences, we found that most patients failed to recognize identical peptides of those sequences, but recognized different variant peptides of the same region. Only seven patients responded to endogenous sequences. We found that several endogenous peptides that failed to be recognized showed no binding to the HLA alleles carried by that given patient, suggesting that mutations selected by immune pressure have led to escape of antigen presentation, as well as direct escape of the CD4+ T cell response. Alternatively, it could have been due to the presence of a different replicating virus in the plasma-since we only obtained proviral sequences. Conclusion: Wild-type and mutant HIV-1 protease epitopes recognized by CD4+ T cells were identified. We also found that most patients failed to recognize their endogenous protease sequences, while they recognized variant sequences. The recognition of non-endogenous sequences could hypothetically be a consequence of targeting a minor HIV-1 population; HERV protease, that contains regions of similarity with HIV-1 protease; or HIV-1 sequences present only in viremic partners. The failure to recognize endogenous sequences is most likely due to immune escape, either at the level of presentation or direct T cell recognition. This may have a pathophysiological consequence on evasion of T cell responses against protease and the fact that it has been considered traditionally a poorly antigenic HIV-1 protein.

Introdução: A Síndrome da Imunodeficiência Adquirida ocorre devido presença do vírus HIV no organismo afetando o sistema imunológico, podendo deteriorá-lo, permitindo a manifestação de infecções oportunistas. Estas infecções podem acometer o Sistema Auditivo Periférico trazendo prejuízo à audição dos indivíduos infectados. A literatura aponta a avaliação da Audiometria em Altas Frequências como um preditor importante para as alterações deste sistema. Objetivo: Caracterizar as manifestações audiológicas em indivíduos com HIV / AIDS submetidos e não submetidos à terapia antirretroviral. Método: A avaliação audiológica foi realizada em 28 indivíduos do GPI com HIV/AIDS, submetidos à terapia antirretroviral; 24 indivíduos do GPII com HIV/AIDS, não submetidos à terapia antirretroviral e 45 indivíduos saudáveis do GC. Os exames audiológicos que compuseram esta pesquisa foram: Audiometria Tonal Convencional, Logoaudiometria, Audiometria em Altas Frequências, Medidas de Imitância Acústica. Resultado: Para as medidas de Imitância Acústica não houve diferença estatisticamente significante para os resultados obtidos entre os grupos, tanto para a Timpanometria, como para os Reflexos Acústicos. Observou-se também, que para os três grupos, a proporção de resultados normais para a Timpanometria é maior, enquanto para os Reflexos Acústicos, a maior proporção foi de resultados alterados. Os grupos GPI e GPII, compostos por indivíduos com HIV/AIDS apresentam alterações tanto na avaliação audiológica convencional, como em altas frequências. Em relação à Audiometria Tonal Convencional, na comparação entre os grupos, observou-se limiares auditivos mais elevados nas frequências de 250 Hz, 1000 Hz, 2000 Hz, 4000 Hz, 6000 Hz e 8000 Hz para os indivíduos com HIV/AIDS. No que diz respeito à Audiometria em Altas Frequências, os resultados obtidos demonstraram, também, limiares auditivos mais elevados em indivíduos com HIV/AIDS nas frequências de 10 KHz, 11,2 KHz, 12,5 KHz, 14KHz, 18 kHz e 20 KHz. Conclusão: Para as Medidas de Imitância Acústica, não foi observada diferença entre os três grupos. Indivíduos com HIV/AIDS apresentam mais alteração na Audiometria Tonal Convencional e na Audiometria em Altas Frequências quando comparados a indivíduos saudáveis, sugerindo, comprometimento do sistema auditivo periférico. Não houve diferença significativa entre indivíduos com HIV/AIDS submetidos e não submetidos à terapia antirretroviral / Introduction: Acquired Immune Deficiency Syndrome occurs as a result of the presence of the HIV virus in the body affecting the immunological system, potentially making it deteriorate, allowing the manifestation of opportunistic infections. These infections can attack the peripheral hearing system causing hearing damage to the infected individuals. Literature indicates High Frequency Audiometry as an important pointer to the alterations of the peripheral hearing system. Objective: To characterize the audiological manifestations in individuals with HIV/AIDS submitted and not submitted to antiretroviral therapy. Method: The audiological evaluation was carried out in 28 individuals of GPI with HIV/AIDS submitted to antiretroviral therapy; 24 individuals of GPII with HIV/AIDS not submitted to the antiretroviral therapy and 45 healthy individuals of GC. The audiological tests that make up this survey were: Conventional Tonal Audiometry, Speech Audiometry, High Frequency Audiometry and Acoustic Immitance Measures. Result: In the measurement of Acoustic Immitance, there was no statistically significant difference in the results obtained amongst the groups, for Tympanometry Test and for Acoustic Reflexes. It was also observed that for the three groups, the percentage of normal results for Tympanometry Test was higher, whilst for Acoustic Reflexes the higher percentage was of altered results.The groups GPI and GPII, formed by individuals with HIV/AIDS, presented alterations in the conventional audiological evaluation as well as in the high frequency one. With regards to the Conventional Tonal Audiometry, in the comparison amongst the groups, it showed higher audiometrics thresholds in frequencies of 250 Hz, 1000 Hz, 2000 Hz, 4000 Hz, 6000 Hz and 8000 Hz for individuals with HIV/AIDS. Regarding High Frequency Audiometry, the results also showed higher audiometrics thresholds in individuals with HIV/AIDS in frequencies of 10 KHz, 11,2 KHz, 12,5 KHz, 14KHz, 18 kHz and 20 KHz. Conclusion: There was no difference in the Measurements of Acoustic Immitance observed amongst the three groups Individuals with HIV/AIDS present more alterations in Conventional Tonal Audiometry and in High Frequency Audiometry when compared to healthy individuals which indicates a compromise on the peripheral hearing system. There was no significant difference between individuals with HIV/AIDS submitted and not submitted to antiretroviral therapy

The human immunodeficiency virus (HIV) epidemic is far from over. Antiretroviral therapy (ART) is effective at suppressing viral replication within a patient but it must be taken daily and is life-long. Therefore, the development of a therapy that could induce drug-free remission or constitute a functional cure is a key focus of HIV research. In this thesis I explore three mechanisms which could lead to more individuals being able to control their viraemia in the absence of ART: (1) T-cell immunity, (2) early initiation of ART, and (3) viral evolution. Firstly, a strong HIV-specific T-cell response has been linked to rare cases of spontaneous viral control, but the extent to which this arm of the immune response contributes to viral control is debated. Several types of data are used to answer this question, including the rate at which the virus evolves to escape the CD8+ T-cell response. I study the frequency of incident immune escape in the largest cohort used for this purpose to date. Secondly, some patients, with characteristics dissimilar to spontaneous HIV controllers, are able to control the virus for years after the interruption of ART that was initiated early in infection. I use mathematical models to investigate a new hypothesis for the differing outcomes of early- and late- initiated ART. Thirdly, since HIV is a relatively new infection of humans it is still adapting to its new host. Recent studies suggest that the virus could be evolving towards decreased virulence at the population level. I study whether the widespread administration of ART has the potential to alter the course of virulence evolution and might result in a further attenuated virus. I conclude by discussing the implications of these results for viral control at the individual level and also for population level epidemic control.

HIV-1 is the causative agent for AIDS and has been a major focus of research for the past two decades. Though there is a combination therapy in place known as the “Highly Active Anti-Retroviral Therapy” (HAART), its usefulness is confounded by the generation of escape mutants, a host of side effects, and its prohibitive cost. The most useful alternative would be the prevention of infection by vaccination. Vaccine research has been focused on the use of recombinant protein sub-units of the virus or combinations thereof to elicit a neutralizing response against the virus. These approaches have mostly resulted in a failure to generate broadly cross reactive neutralizing response against primary strains of the virus. The work reported herein is aimed at designing a rigidified version of gp120/gp120 derivatives and understanding the scope of the various antigenic regions in gp120 in generating a neutralization response. Chapter one discusses some general features of the virus and the immune system. The general nature of AIDS, its spread and its immunological characteristics are also described in this chapter. Chapter two discusses the design and NMR structural analysis of gp120 bridging sheet peptide mimics in methanol and water. The structure of gp120 can be loosely divided into two domains (the outer domain and the inner domain) that are linked together by a discontinuous four stranded antiparallel beta sheet known as the bridging sheet. The bridging sheet is known to overlap with the coreceptor binding site of gp120 and hence is a suitable target for designing virus-entry inhibitors. 17b, a neutralizing antibody isolated from an infected individual, is known to bind to this region of gp120. Our aim in this part of the work was to design a four stranded antiparallel beta sheet, based on the sequence of the bridging sheet, that would contain most of the residues involved in 17b binding. NMR and CD studies confirmed that the peptide was well structured in methanol but the structure was largely lost on addition of aqueous solvent. A small population of the peptide was found to be well-folded in aqueous solution. Chapter three discusses the design and characterization of a gp120-CD4D12 single chain. It is well known that the conformation of gp120 changes upon binding CD4 to expose cryptic epitopes, known as CD4i epitopes. In this work we report the generation of a single chain gp120-CD4 construct that has the cryptic epitopes exposed. The construct bound to 17b, a conformation specific antibody against the bridging sheet of gp120, a cryptic epitope, as well as a non-covalent complex of gp120:CD4D12. There was also very insignificant secondary structural change in gp120 upon complex formation with CD4D12 as observed by CD spectroscopy. Immunological studies with DNA and protein vaccination in guinea-pigs indicated that though 17b like antibodies are generated after immunization, they did not contribute towards the neutralization of primary isolates of the virus. It was also observed that it was the anti-CD4D12 antibodies that were responsible for the neutralization by the sera. These studies indicated towards the inability of the bridging sheet to generate effective neutralization response in case of vaccination with gp120/CD4 complexes. Chapter four discusses the design of a mimic of the gp120/CD4 complex. Since it was seen from our previous work that gp120/CD4 complexes generate a large fraction of antiCD4 antibodies and hence are unsuitable for vaccination purposes, we generated a construct with the minimal binding region of CD4. The small fragment of CD4 spanning from 21st residue to 64th residue was inserted in the V1/V2 loop of gp120. The insertion site was designed based on the region of gp120 closest to this fragment and capable of tolerating insertions. This protein did not bind to 17b as well as gp120/CD4 complex but showed a higher binding compared to full length gp120. Further immunological characterization with this protein revealed that it was not capable of generating neutralizing antibodies against the virus. Chapter five discusses the design and execution of a SPR based solution phase competition experiment to find the solution phase binding constant of CD4 and CD4 analogs to gp120. A major problem during the analysis of binding data obtained by SPR is the accurate determination of Rmax, a parameter needed to obtain an accurate equilibrium dissociation constant. In this chapter we have developed a binary as well as a ternary solution phase SPR based assay to accurately determine a solution phase equilibrium binding constant. The binding constants were determined for gp120 binding to CD4D12 and other CD4 analogs. To confirm the validity of the assay, a control antigen:antibody interaction whose equilibrium dissociation constant has been determined by other methods has been used as a test case. Chapter six discusses the design and characterization of V3 peptides inserted in the loop regions of E. coli Thioredoxin (Trx). Trx has earlier been used to display random peptide libraries between the 33rd and the 34th residue. We have constructed three constructs where the peptide has been inserted between the 33rd and 34th residue, between the 74th and 75th residue and between the 84th and 85th residue. The insertion between 74th and 75th position (74V3Trx) was found to be superior to the other two and would be a suitable alternative for display of a random peptide library. The binding of these constructs to 447-52D, a V3 peptide specific antibody was characterized. These were also characterized immunologically, and 74V3Trx was found to generate weakly neutralizing activity against the MN strain of HIV-1. Competition experiments with 447-52D with these sera indicated that there were antibodies generated that could compete out 447-52D binding to gp120 but not in sufficient concentration to provide broad neutralization. Appendix 1 discusses the rational design of disulfides to stabilize proteins based on the analysis of naturally occurring disulfides. In our attempts to design a rigidified version of gp120 we had designed disulfides in gp120 based on its crystal structure. Many of these were disulfides that would span antiparallel adjacent strands. In order to improve the design principles, we analyzed naturally occurring disulfides that span antiparallel adjacent strands and characterized them in terms of their positional preference in a beta sheet. It was found that these disulfides mostly occur on edge strands and are found exclusively between non-hydrogen bonded registered pairs of adjacent antiparallel strands. Mutagenesis on Thioredoxin was performed to verify our results. It was found that disulfides designed between the non-hydrogen bonded pairs of antiparallel strands could significantly stabilize the protein whereas the ones between hydrogen bonded pairs destabilized the protein.

Thesis (MSc. (Physiology)) -- University of Limpopo, 2016 / Relevance: An increase in the number of HIV positive patients receiving HAART raises important concerns about the metabolic impact of these regimens. The treatment effectively reduces viral load and increase CD4+ count; unfortunately it seems to disrupt carbohydrate and lipid metabolic pathways thereby increasing the risk for CDL by placing an already chronically ill HIV population at risk of more chronic diseases. As a developing country, accessibility to safer regimens of HAART is limited thus patients exposed to toxicities from long term exposure to sub-optimal regimens are even at greater risk. The aim of this study was to assess the long term effects of HAART on biochemical parameters and body composition as an indication of carbohydrate and lipid metabolism. Methods: A prospective cohort of 87 patients receiving HAART for 12 months or more was conducted at baseline and follow-up. Venous blood was collected after an overnight fast. An automated enzymatic colorimetric test was used to analyse plasma glucose and serum TC, HDL-C and TG. The LDL-C levels were calculated from TC and HDL-C. Leptin levels were analysed using human leptin radioimmunoassay kit. Insulin was analysed using an automated access ultrasensitive insulin assay. Anthropometric measurements were taken for the determination of body fat distribution and BMI. All statistical analyses were performed using SPSS version 23. Results: Total cholesterol, LDL-C, and waist circumference significantly decreased from baseline to follow-up (p<0.05). Triglycerides and LDL-C levels were significantly affected by durations between 24–47 and 49–72 months respectively. There were no significant changes in the mean levels of leptin observed within the two lines of regime. Mean leptin levels were 11.36±8.52 ng/ml and 9.67±6.42 ng/ml at baseline and follow-up respectively. Furthermore, the duration of HAART significantly affected BMI and WC at 49–72 months. Patients that met the criteria for diagnosis of DM were only found in PI containing regimens at 6.3% and 5.9% baseline and follow-up respectively. In the first line regimen, the prevalence of DM was only found at follow-up. Conclusion: The present study demonstrated that longer duration between months 49–72 has significant negative effects on the glucose and lipid metabolism of HIV positive patients. The study also highlighted that patients on combinations containing PIs and NRTIs such as stavudine and zidovudine are at higher risk of developing metabolic diseases. / University of Limpopo

"Although the number of new infections has dramatically decreased during the last ten years, portraying this country [Uganda] as the 'AIDS miracle', the number of people already infected and progressing to AIDS is increasing. Acces to anti-retroviral (ARV) drugs, as well as to medicines for treatment of opportunistic infections (TOI), is essential for people living with HIV/AIDS (PLWHA) to enjoy their right to life and health. Although access to these essentail medicines forms part of the core content of the right to health, which states should be able to provide irrespective of their available resources, slightly more than half of the people in need in Uganda were accessing them in June 2005. Of 63,896 PLWHA accessing ARVs, still 83.5 percent are paying the medicines out of their pockets. This is despite the fact that Uganda receives funds from various sources, among which Global Fund to Fight AIDS, Tuberculosis and Malaria (GF) and the US President's Emergency Plan for AIDS Relief (PEPFAR). Although the cost of ARV treatment in Uganda has dramatically decreased since 1997, the price of treatment remains still unaffordable for most Ugandans. ... This study comprises five chapters. The present chapter exposes the problem, the objectives of the study and the research questions, reviews the literature available on the subject, outlines the study's structure, proposes a methodology and points out the study's limitations and relevance. Chapter two sets out the international legal framework of the study. It oulines the scope of the right of PLWHA to access to essential treatment under different international instruments of relevance for Uganda and its connection with other human rights. The chapter also assesses the implications of this right for state and non-state actors. Chapter three sets out the national legal, policy and judicial framework. It explores the action taken by the various branches of the government in addressing the international obligations with regard to access essential treatment. This chapter will also look at the role played by other relevant stakeholders in the realisation of this right in Uganda. Chapter four analyses the various obstacles that impede the realisation of this right at national level, taking into account the globalisation process, the political situation of Uganda, as well as other socio-economic factors. Chapter five provides the final conclusions and recommends legal, judicial and administrative channels towards the realisation of the right to access essential treatment for OLWHA in Uganda." -- Introduction. / Thesis (LLM (Human Rights and Democratisation in Africa)) -- University of Pretoria, 2005. / [Prepared under the supervision of] Dr. Ben Kiromba Twinomugisha, Makerere University / http://www.chr.up.ac.za/academic_pro/llm1/dissertations.html / Centre for Human Rights / LLM

Yes / Emtricitabine (ECB) afforded dimorphic cocrystals (Forms I, II) of benzoic acid (BA), whereas with p-hydroxybenzoic acid (PHBA), p-aminobenzoic acid (PABA) are resulted in as high Z'' cocrystals. Intriguingly, the Z'' of cocrystals are trends from two to fourteen based on the manipulation of functional groups on the para position of BA (where H atom is replaced with that of OH or NH2 group). ECB‒PABA cocrystal consists of six molecules each and two water molecules in the asymmetric unit (Z''=14) with 2D planar sheets represents the rare pharmaceutical cocrystal. The findings suggest that the increment of H bond donor(s) systematically via a suitable coformer are in correspondence with attaining high Z'' cocrystals. Further, solid state NMR spectroscopy in conjunction with single crystal X-ray diffraction are demonstrated as significant tools to enhance the understanding of the number of symmetry independent molecules in the crystalline lattice and provide insights to the mechanistic pathways of crystallization. / Department of Science and Technology (DST) Fund for improvement of S & T Infrastructure (FIST) with grant no. SR/FST/CST-266/2015(c) to PS and VP. AN and VV acknowledge the Government of India under National Overseas Scholarship (2012-13) and High Commission of India, London UK for PhD studentship.

This study attempted to identify personal (patient-related) factors influencing anti-retroviral therapy (ART) adherence in Addis Ababa, Ethiopia. A quantitative, descriptive, cross-sectional and analytical design was used. Structured interviews were conducted with 355 ART patients. The findings revealed that stigma, discrimination, depression and alcohol use negatively affected patients’ ART adherence levels. However, patients’ knowledge levels had no influence on their ART adherence levels, contrary to other researchers’ reports. Addressing stigma and discrimination at community levels might enhance patients’ abilities to take their medications in the presence of others. Healthcare professionals should be enabled to diagnose and treat depression among ART patients during the early stages. Non-adherent ART patients should be counseled about possible alcohol abuse. / Health Studies / M.A. (Public Health with specialisation in Medical Informatics)

This study attempted to identify personal (patient-related) factors influencing anti-retroviral therapy (ART) adherence in Addis Ababa, Ethiopia. A quantitative, descriptive, cross-sectional and analytical design was used. Structured interviews were conducted with 355 ART patients. The findings revealed that stigma, discrimination, depression and alcohol use negatively affected patients’ ART adherence levels. However, patients’ knowledge levels had no influence on their ART adherence levels, contrary to other researchers’ reports. Addressing stigma and discrimination at community levels might enhance patients’ abilities to take their medications in the presence of others. Healthcare professionals should be enabled to diagnose and treat depression among ART patients during the early stages. Non-adherent ART patients should be counseled about possible alcohol abuse. / Health Studies / M.A. (Public Health with specialisation in Medical Informatics)