Magister Public Health - MPH / Aim: This study aimed to evaluate the effectiveness of the Mobile HIV/AIDS Treatment Teams in initiating and treating patients with HAART at fixed primary health care clinics Amajuba District.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The objective was to understand the significance for the family caregiver before of the child care that has HIV / AIDS in antiretroviral therapy (ART). It was phenomenological qualitative research based on theoretical-philosophical - methodological Martin Heidegger. The subject were family caregivers of children that realize monitored in the pediatric clinic at the Hospital Universitário de Santa Maria (HUSM / RS / BRAZIL). The data production occurred in the period of January to July 2013 through phenomenology interviews with 10 family caregivers. It was developed Heidegger's analysis and in the vague understanding and median the family of child with HIV / AIDS in ART unveiled that the experience of care means that once started therapy the child have a normal life, doing all that other children do. It follows a routine, it have time to give the medication and other care. In the begin it was difficult until we hit the medication and it had difficulties with the intake. It was difficult to live with the disease not knowing where to turn, it needed of the help of family members and professionals. With time it observes, learns and starts calm because the child takes the medicine. It has afraid of prejudice, why hide the diagnosis of both the child and of other family. It has to pay more attention to the child than himself. In interpretive analysis the family reveals being caregiver, it shows that the child is and does everything who the others revealing the way of being to be in the impersonality. It establishes a routine to keep the treatment and health of the child remaining committed to the world of occupations. It is shown in the mode of curiosity when he observes the daily care of the child and he learns and it proves to be quiet when the child accepts and asks the drug. So the child has a normal life that keeps her in the public interpretation of the impersonal. Given the fact of to live with the disease, the experience of being - family - caregiver unfolds in the mode of factuality because it is before a fact launched and show-be-with when counts with the help of other family members. This experience is shown in the layout mode of fear, permeating through fear, horror and terror when think in the diagnostic revelation in the consequences that can result in the child's daily life and prejudice, concealing the child's diagnosis, remaining in the stillness. The be - family - caregiver engage with the child care and it leave to care for themselves, losing himself in the mode of being of inauthenticity. The inauthenticity present in the everyday care bears the be - family - caregiver to do as others think that has to be done, It does not revealing in its uniqueness. It was highlight the need of health professionals to develop dialogue aimed not only to medication and treatment, but also that facilitate the understanding of situation through educational groups, consultations and workshops. It is suggested to stimulate the involvement of others people next to the child that can realize and divide this care with the family caregiver. / O objetivo foi compreender a significação para o familiar cuidador diante do cuidado à criança que tem HIV/aids em terapia antirretroviral (TARV). Investigação qualitativa fenomenológica fundamentada no referencial teórico-filosófico-metodológico de Martin Heidegger. Sujeitos da pesquisa foram familiares cuidadores de crianças que realizam acompanhamento no ambulatório de pediatria no Hospital Universitário de Santa Maria (HUSM/RS/BRASIL). A produção dos dados ocorreu no período de janeiro a julho de 2013, por meio de entrevista fenomenológica com 10 familiares cuidadores. Desenvolveu-se análise heideggeriana, sendo que, na compreensão vaga e mediana o familiar da criança que tem HIV/aids em TARV, desvelou que a vivência do cuidado significa que depois que iniciou a medicação a criança leva uma vida normal, faz tudo o que as outras crianças fazem. Obedece a uma rotina, tem hora certa para dar a medicação e para os demais cuidados. No começo foi difícil enquanto não acertaram a medicação e tinham dificuldades com a ingesta. Foi difícil conviver com a doença, não saber a quem recorrer, precisou da ajuda dos familiares e dos profissionais. Com o tempo observa, descobre, aprende e fica tranquilo, pois a criança aceita o remédio. Tem medo do preconceito, por isso oculta o diagnóstico tanto da criança quanto da família e dos outros. Tem que dar mais atenção à criança do que a si mesmo. Na análise interpretativa o familiar se revela sendo cuidador mostra que a criança é e faz tudo como todas as outras, desvelando-se no modo de ser da impessoalidade. Estabelece uma rotina para manter o tratamento e a saúde da criança mantendo-se empenhado no mundo das ocupações. Se mostra no modo da curiosidade quando observa o cotidiano do cuidado à criança e assim aprende e com isso, revela-se tranquilo quando a criança aceita e solicita o medicamento. Isso faz com que a criança tenha uma vida normal o que a mantém na interpretação pública do impessoal. Diante do fato de ter que conviver com a doença, a vivência de ser-familiar-cuidador se desvela no modo da facticidade, pois está diante de um fato lançado e se mostra ser-com quando conta com o auxílio dos demais familiares. Nessa vivência se mostra no modo de disposição do medo, perpassando pelo pavor, horror e terror quando pensa na revelação do diagnóstico, nas consequências que isso possa acarretar no cotidiano da criança e no preconceito, assim, acaba ocultando o diagnóstico da criança, permanecendo na silenciosidade. O ser-familiar-cuidador ao se ocupar com os cuidados com a criança deixa de cuidar de si, perdendo-se no modo de ser da inautenticidade. A inautenticidade presente na cotidianidade do cuidado carrega o ser-familiar-cuidador para fazer como os outros acham que tenha que ser feito, não se revelando na sua singularidade. Salienta-se a necessidade dos profissionais de saúde em desenvolver diálogo voltado não apenas à medicação e tratamento, mas também que facilitem a compreensão da situação por meio de grupos educativos, consultas e oficinas. Sugere-se estimular o envolvimento de outras pessoas próximas à criança que possam realizar e dividir esse cuidado com o familiar cuidador.

Depuis la description des premiers cas de SIDA pédiatriques en 1983, d’importants progrès ont été réalisés dans la compréhension des mécanismes de transmission, puis dans la prévention de celle-ci, et dans la connaissance de l’histoire naturelle de l’infection par le VIH chez l’enfant. Depuis 1996 les multithérapies ARV ont permis une diminution considérable de la transmission verticale et de la morbidité et mortalité des enfants infectés par le VIH.<p>Les buts de ce travail ont été :<p>• d’évaluer, dans le contexte de l’offre de soin mise en place dans un centre de référence,<p>l’impact de l’administration prophylactique des traitements ARV pendant la grossesse sur la transmission verticale du virus.<p>• de déterminer si l’instauration précoce d’un traitement ARV chez les enfants infectés à la naissance et encore asymptomatiques améliorait le devenir de l’enfant.<p>• de contribuer à l’évaluation de l’impact de l’exposition à la maladie maternelle et aux traitements ARV sur le devenir des enfants non infectés nés de mères infectées par le VIH.<p><p>Une étude rétrospective portant sur les enfants nés de mères infectées par le VIH et suivis à l’hôpital St-Pierre entre 1986 et 2002, nous a permis de comparer 3 cohortes de naissance correspondant à différents types de prise en charge. Nous avons pu montrer que le taux de transmission a diminué globalement de 10% durant la période précédant l’administration de prophylaxie ARV à 5% durant la troisième période où les multithérapies étaient recommandées en prophylaxie durant la grossesse. Nous avons montré<p>que chez les mères qui ne bénéficiaient pas de prophylaxie ARV le taux de transmission avait augmenté significativement entre 1986 et 2002; le plus souvent suite à une prise en charge trop tardive de la grossesse, à un dépistage tardif de la séropositivité maternelle, ou à une mauvaise compliance au traitement.<p>Chez le nouveau-né infecté par le VIH, la multiplication virale est beaucoup plus importante<p>et prolongée que lors de la primo-infection chez l’adulte. Parallèlement, l’évolution clinique de l’infection peut être rapide dans un quart des cas, et aboutir au SIDA ou au décès avant l’âge de 1 an, sans qu’il existe de bons facteurs prédictifs de cette évolution défavorable en début de vie. Jusqu’en 2007, les différentes recommandations internationales indiquaient de débuter un traitement chez les nourrissons infectés lors d’apparition de symptômes cliniques ou d’immunodépression. Cependant dès 1996, certains centres dans des pays industrialisés, dont l’équipe de pédiatrie du CHU St Pierre, ont décidé d’initier un traitement ARV chez tous les nourrissons infectés dès confirmation du diagnostic. En 2006, nous avons initié une étude rétrospective multicentrique incluant 13 cohortes européennes visant à étudier l’impact du traitement précoce sur l’évolution clinique et biologique de l’enfant. Les données de 210 enfants,nés entre 1996 et 2004 et infectés à la naissance ont été analysées, et ont permis de dé4<p>montrer que les enfants traités avant l’âge de 3 mois avaient un risque de développer un sida ou de décéder 5 fois inférieur aux enfants traités après cet âge. Des résultats similaires ont été observés dans une étude randomisée réalisée en Afrique du Sud et publiée simultanément. Depuis, les recommandations internationales ont été revues<p>et préconisent la mise sous traitement de tous les nourrissons infectés. L’analyse des données biologiques a permis de montrer que la réponse virologique immédiate était plus rapide avec un pic de charge virale moins élevé et que la chute des lymphocytes CD4 était moins prononcée lorsque le traitement était débuté précocement.<p>Avec la généralisation de la prophylaxie ARV pendant la grossesse, le nombre d’enfants exposés in utero au VIH mais indemnes de l’infection a considérablement augmenté.<p>Des études, menées principalement dans des pays en développement, ont révélé un risque accru de morbidité et de mortalité infectieuse ainsi que la survenue d’infections sévères inhabituelles chez ces enfants. Nous avons été frappés durant le suivi de ces enfants par la survenue d’un nombre élevé d’infections néonatales causées par le streptocoque du groupe B (GBS). La comparaison avec le taux d’infection observé dans une population contrôle (estimé sur base des naissances survenues pendant la même période dans le même hôpital) nous a permis de décrire une incidence 19 fois supérieure d’infection à GBS chez les enfants exposés au VIH et non infectés que chez les enfants contrôles. Il s’agit du premier travail publié évoquant une susceptibilité accrue aux infections des enfants exposés non infectés dans un pays industrialisé.<p>En conclusion, la prophylaxie ARV pendant la grossesse et en début de vie a permis de diminuer considérablement la transmission verticale de l’infection à VIH. Un dépistage manqué, une prise en charge tardive de la grossesse, ou la mauvaise adhérence au traitement sont encore responsables d’infection du nouveau-né. Lors de confirmation<p>d’infection du nourrisson par le VIH, il est très important de débuter un traitement le plus rapidement possible afin de contrôler rapidement la multiplication virale, de maintenir une bonne immunité et de prévenir le développement de la maladie. Enfin, en l’absence d’infection du nourrisson par le VIH, il est important de poursuivre le suivi pendant les premières années de vie puisqu’il semble que les enfants exposés au<p>VIH et non infectés soient plus susceptible aux infections sévères. Ceci a été démontré en ce qui concerne les infections néonatales à GBS. / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Magister Artium (Social Work) - MA(SW) / The burden of HIV disease is concentrated in sub-Saharan Africa and South Africa (SA) is particularly affected. Whilst there have been many studies conducted on the biomedical and socio-psychological aspects of HIV and AIDS, insufficient attention has been paid to the quality of life of those infected with the virus. The primary purpose of this study was to determine the predictors of quality of life enjoyment and satisfaction (Q-LES) of individuals living with HIV and or AIDS and those on anti-retroviral treatment or being prepared for it. Further, the study determined the relationship between psychological distress and Q-LES of HIV positive individuals because psychological distress is reported to contribute substantially to the burden of the disease in sub-Saharan Africa, including SA. This quantitative study used a battery of questionnaires administered to 121 participants in an out-patient clinic setting. The main hypothesis tested in this study is: psychological distress is a strong predictor of Q-LES. The Hospital Anxiety and Depression Scale (HADS) was used to screen for psychological distress and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) to assess the various components of QoL. A purposive sampling strategy was used to recruit participants into the study. Data analysis included descriptive and inferential statistics using SPSS to test the hypothesis. Of the total sample (N=121), 74% were females. The study found that a large proportion (49.5%) of the sample within the age group 25-49 years old had significant presence of psychological distress. Those not on ART yet were significantly affected (66%). The relationship between Q-LES subscales and psychological distress was significant (p< 0.01). The results show that psychological distress was significantly prevalent among HIV positive individuals and it was the strongest predictor of Q-LES among the study participants. Modifying the current psychological intervention programmes, in the public health clinics, for individuals vi infected with the HI virus will assist in improving the current health outcomes and also help to achieve better Quality of Life outcomes.

The effectiveness of antiretroviral therapy (ART) transformed the pediatric HIV epidemic. The disease changed significantly over the course of three decades: while early in the epidemic it was almost always fatal, it has become a chronic condition. This study examined how perinatally-infected youth experience the impact of HIV in their lives. A qualitative study using interpretative phenomenological analysis (IPA) was conducted. Twenty in-depth interviews were carried out among 12 women and 8 men aged 18 to 30 years in Puerto Rico. These were conducted in Spanish, audio-recorded, transcribed and translated into English. While narrating their experiences, participants were interpreting what the situation meant to them and how they make sense of it. Three topics emerged: (1) perception and response to treatment and illness, particularly their lived experiences with ART; (2) disclosure experiences; and (3) family matters. Most participants challenged their therapy, in most cases to force their caregivers to disclose their status. Problems with adherence were attributed to busy schedules or forgetfulness. Participants experienced the disfiguring adverse effects of ART, which they endured for years without being informed that ART was the cause of these. Participants’ experiences with disclosure demonstrated the importance of validating them as individuals capable of managing their health. The paternalistic approach of withholding their diagnosis to spare them suffering resulted in increased anxiety. Participants acknowledged the difficulties of revealing their HIV status to their partners. They referred to family and friends as essential in coping with HIV. However, some encountered discrimination and stigma within their families. Participants who had suffered the loss of their parents found other parental figures such as adoptive parents or other family members. Most participants expressed a desire to have children. Perinatally HIV-infected youth will require health services for the rest of their lives. The adult health care into which they transition should consider their needs and journey. Services should consider including family members. This study underscores the need for improved access to mental health services. It is also essential to transcend medical treatment and develop a broader perspective of health care. Health care services should include reproductive decision-making counselling services.

The human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) is a worldwide pandemic that affects the lives of millions of people across all ages. Its devastating effects are far-reaching and affect all aspects of an individual’s daily life. HIV/AIDS is responsible for widespread clinical manifestations involving the head and neck. Disorders of the auditory and vestibular systems are often associated with HIV/AIDS, however the extent and nature of these vestibular manifestations is still largely unknown. The main aim of this research study was to investigate vestibular functioning and pathology in adults with HIV/AIDS. This was achieved through three main research steps: a systematic literature review of the body of peer-reviewed literature on HIV/AIDS related vestibular manifestations and pathology, a description and comparison of vestibular involvement in adults with and without HIV/AIDS and an investigation to determine if HIV/AIDS influence the vestibulocollic reflex (VCR) pathways. For the first study a systematic literature review related to vestibular findings in individuals with HIV infection and AIDS was conducted. A varied search strategy was used across several electronic databases to identify relevant peer-reviewed reports in English. Several databases (Medline, Scopus and PubMed) and search strategies were employed. Where abstracts were not available, the full paper was reviewed, and excluded if not directly relevant to the study’s aims. Articles were reviewed for any HIV/AIDS associated vestibular symptoms and pathologies reported. For the second and third study, a cross-sectional, quasi-experimental comparative research design was employed. A convenience sampling method was used to recruit subjects. The sample consisted of 53 adults (29 male, 24 female, aged 23-49 years, mean = 38.5, SD = 4.4) infected with HIV, compared to a control group of 38 HIV negative adults (18 male, 20 female, aged 20-49 years, mean = 36.9, SD = 8.2). A structured interview probed the subjective perception of vestibular complaints and symptoms. Medical records were reviewed for cluster of differentiation 4+ (CD4+) cell counts and the use of antiretroviral (ARV) medication. An otologic assessment and a comprehensive vestibular assessment (bedside assessments, vestibular evoked myogenic potentials, ocular motor and positional tests and bithermal caloric irrigation) were conducted on all subjects. The systematic literature review identified 442 records, reduced to 210 after excluding duplicates, reviews, editorials, notes, letters and short surveys. These were reviewed for relevance to the scope of the study. There were only 13 reports investigating vestibular functioning and pathology in individuals affected by HIV/AIDS. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance. The second study showed an overall vestibular involvement in 79.2% of subjects with HIV in all categories of disease progression, compared to 18.4% in those without HIV. Vestibular involvement increased from 18.9% in the Centers for Disease Control and Prevention (CDC) category 1 to 30.2% in category 2. Vestibular involvement was 30.1% in category 3. There was vestibular involvement in 35.9% of symptomatic HIV positive subjects and 41.5% in asymptomatic HIV positive subjects. Individuals with HIV were 16.6 times more likely to develop vestibular involvement during their lifetime, than among individuals without this disease. Vestibular involvement may occur despite being asymptomatic. The third study showed that abnormal cervical vestibular evoked myogenic potentials and caloric results were significantly higher in the HIV positive group (p=.001), with an odds ratio of 10.2. Vestibulocollic reflex and vestibulo-ocular reflex involvement increased with progression of the disease. There were more abnormal test results in subjects using ARV therapies (66.7%) compared to those not using ARV therapies (63.6%), but this difference was not statistically significant. Vestibular involvement was significantly more common in subjects with HIV than among those without this disease. This disease and its associated risk profile include direct effects of the virus on the vestibular system as demonstrated by postmortem studies. Opportunistic infections may compromise the functioning of the sensory and neural structures of hearing and the vestibular system indirectly, causing vertigo, dizziness or disequilibrium. Ototoxicity may also be related to vestibular dysfunction, due to the ototoxic nature of certain ARV medications. HIV/AIDS influence not only the vestibulo-ocular reflex, but also the vestibulocollic reflex pathways. Primary health care providers could screen HIV positive patients to ascertain if there are symptoms of vestibular involvement. If there are any, then they may consider further vestibular assessments and subsequent vestibular rehabilitation therapy, to minimize functional limitations of quality of life. / Thesis (DPhil)--University of Pretoria, 2014. / lk2014 / Speech-Language Pathology and Audiology / DPhil / Unrestricted

Aujourd'hui, l'un des modèles de souris humanisées le plus robuste est obtenu en injectant des cellules souches hématopoïétiques humaines (HSC) issues de foie fœtal humain et en implantant du thymus fœtal autologue. Ce modèle, appelé BLT (Bone marrow/Liver/Thymus), s'est révélé capable de supporter une reconstitution, une maturation et une sélection optimales des cellules T. Les souris BLT sont utilisées pour de nombreuses études telles que la compréhension de la biologie du VIH ou plus récemment en médecine régénérative. Grâce à ce modèle, nous avons pu d’une part étudier le rôle des cellules dendritiques plasmacytoïdes (pDC) lors de l’infection par le VIH mais aussi mieux comprendre la formation in vivo de tératomes lors de l’utilisation d’iPSC. Cependant, l'une des principales limites de cette technique réside dans l'obtention du tissu fœtal. Ici, nous avons décrit un nouveau protocole de souris humanisées greffées avec du thymus humain en utilisant des matériaux plus accessibles: du thymus humain retiré lors d’une chirurgie cardiaque chez des nouveaux-nés ou des enfants, et des HSC de sang de cordon. Des morceaux de ces thymus ont été implantés dans les quadriceps de souris immunodéficientes, après avoir été mis en culture. Ces souris CCST (Cord blood and Cardiac Surgery Thymus) ont permis une prise de greffe importante et un meilleur développement des lymphocytes T humains que les souris humanisées sans thymus. Les lymphocytes T des souris CCST et BLT ont montré une fonction similaire, évaluée par des tests de prolifération ex vivo et par rejet de lignées de cellules leucémiques allogéniques in vivo. Nous avons testé l’intérêt de cette nouvelle stratégie dans le modèle de l’infection au VIH-1, qui représente le modèle type de l’utilité des BLT. Nous avons montré que les souris CCST sont sensibles à l'infection par le VIH-1 par voie muqueuse ou intrapéritonéale, comme l'indique la détection de l'ADN du VIH et des cellules p24 +, similairement aux souris BLT. Les souris CCST ont présenté des réponses de lymphocytes T spécifiques du VIH-1 ex vivo plus efficaces que les BLT. Lors du traitement antirétroviral, les souris CCST, comme les BLT, ont vu leur charge virale diminuer. Ces résultats démontrent que les souris CCST représentent une alternative au modèle de souris BLT classique. Ces thymus, éthiquement plus facile à obtenir, peuvent être utilisés pour générer un grand nombre de souris par rapport aux thymus fœtaux. / Immunodeficient mice engrafted with human immune system provide an exciting in vivo model for a better understanding of its functioning and for development of new therapies. Today, one of the most robust humanized mouse model is achieved by injecting human hematopoietic stem cells (HSC) from fetal liver along with an implantation of autologous fetal thymic tissue. This model, called BLT, was shown to be able to support an optimal T cell reconstitution, maturation and selection. BLT mice are extensively used for many studies such as understanding HIV biology or in regenerative medicine. Indeed, our work used BLT mice on one hand to study the role of plasmacytoid dendritic cells (pDC) during the HIV infection and on the other hand to better understand the formation of teratomes from iPSCs in vivo. However, one of the biggest limitations of this technique is the procurement of the fetal tissue. Here we describe a new protocol to do humanized mice engrafted with human thymus pieces by using more accessible materials: human thymus obtained during cardiac surgery and cord blood HSC. Indeed, thymus is spontaneously removed during cardiac surgery in neonates and young children, thus it is an easy and ethical way to obtain this tissue. Those thymuses pieces were implanted in the quadriceps of a immunodeficient mice, after being put in culture. CCST mice (Cord blood and Cardiac Surgery Thymus) exhibited a significant engraftment of T-cells, compared to humanized mice without thymus. T-cells from both CCST and BLT mice showed a similar function as evaluated by proliferation assays upon PHA stimulation ex vivo and rejection of allogeneic leukemic cells lines in vivo. CCST mice were susceptible to HIV-1 infection via mucosal or intraperitoneal route, as shown by detectable viral load, HIV DNA and p24+ cells, at similar levels to those of BLT mice. Importantly, CCST mice displayed more effective ex vivo HIV-1-specific T-cell responses compared to BLT. Upon antiretroviral treatment, CCST mice, like BLT, were able to diminish the viral load. Our data suggest that CCST mice represent an alternative to the regular BLT mouse model. Those easy-to-access thymuses can be used to generate a large number of mice compared to fetal thymuses.

Background: IPT is an effective, safe and feasible disease prevention scheme that should be administered for all PLHIV living in areas with high latent TB prevalence. Objective: To assess the impact of isoniazid in the incidence of tuberculosis among HIV infected individuals in Addis Ababa. Methods: A case control study design was undertaken among 489 HIV and TB infected patients in Addis Ababa from January 2008 to December 2010. Results: Tuberculosis incidence rate among those who developed TB after completing 6-9 month isoniazid preventative therapy was17.14 PYO compared to 10.28 PYO among those who were not. Isonizide reduced the chance of developing tuberculosis among HIV infected patients (OR= 0.072; 95% CI 0.044, 0.12). Age (AOR= 0.14; 95% CI 0.03, 0.97) and sex (AOR= 1.86; 95% CI 1.02, 2.23) of the patient, CD4 count at HIV diagnosis (AOR= 0.21; 95% CI 0.13, 0.31), clinical stage of HIV illness (AOR= 1.22; 95% CI 1.09, 1.84) and past tuberculosis history (AOR = 1.97; 95% CI 1.24, 3.67) were major factors associated with tuberculosis incidence. Conclusions: INH prophylaxis was associated with lower incidence of tuberculosis among PLHIV. / Health Studies / M. Public Health

Using non-experimental descriptive exploratory survey, this study sought to find out factors associated with delayed entry into HIV medical care among HIV positive people who are aware of their status. A quantitative design was used and a structured questionnaire was used as the data collection instrument. Respondents were patients in a hospital’s Opportunistic Infection Department whose hospital records indicated that they were HIV positive during the time of the study. The study found out that as much as 71.6% (n =43) first entered HIV medical care more than 12 months after testing HIV positive while 40% (n = 24) did so as a result of illness. Low education levels, unemployment and being single are associated with delayed entry into HIV medical care. A percentage of the population uses and trusts non-biomedical approaches to dealing with HIV/AIDS. Being diagnosed HIV positive is therefore not necessarily a strong reason enough for one to immediately enter into medical care. Intensive health education needs to be done at work places, health facilities, schools, through print and electronic media, churches and other community settings to equip the population with knowledge of the advantages of early entry into HIV care. / Health Studies / M.A. (Public Health)

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Background: Despite the effort of scientific research on HIV therapies and to reduce the rate of HIV infection, AIDS remains one of the major causes of death in the world and mostly in sub-Saharan Africa. To date, neither a cure nor an HIV vaccine had been found and the disease can only be managed by using High Active Antiretroviral Therapy (HAART) if detected early. The need for an effective early diagnostic and non-toxic treatment has brought about the necessity for the discovery of additional HIV diagnostic methods and treatment regimens to lower mortality rates. Antimicrobial Peptides (AMPs) are components of the first line of defense of prokaryotes and eukaryotes and have been proven to be promising therapeutic agents against HIV. Methods: With the utility of computational biology, this work proposes the use of profile search methods combined with structural modeling to identify putative AMPs with diagnostic and anti-HIV activity. Firstly, experimentally validated anti-HIV AMPs were retrieved from various publicly available AMP databases, APD, CAMP, Bactibase and UniProtKB and classified according to super-families. Hidden Markov Model (HMMER) and Gap Local Alignment of Motifs (GLAM2) profiles were built for each super-family of anti- HIV AMPs. Putative anti-HIV AMPs were identified after scanning genome sequence databases using the trained models, retrieved AMPs, and ranked based on their E-values. The 3-D structures of the 10 peptides that were ranked highest were predicted using 1-TASSER. These peptides were docked against various HIV proteins using PatchDock and putative AMPs showing the highest affinity and having the correct orientation to the HIV -1 proteins gp120 and p24 were selected for future work to establish their function in HIV therapy and diagnosis. Results: The results of the in silica analysis showed that the constructed models using the HMMER algorithm had better performances compare to that of the models built by the GLAM2 algorithm. Furthermore, the former tool has a better statistical and probability explanation compared to the latter tool. Thus only the HMMER scanning results were considered for further study. Out of 1059 species scanned by the HMMER models, 30 putative anti-HIV AMPs were identified from genome scans with the family-specific profile models after the elimination of duplicate peptides. Docking analysis of putative AMPs against HIV proteins showed that from the 10 best performing anti-HIV AMPs with the highest E-scores, molecules 1,3, 8, and 10 firmly bind the gp120 binding pocket at the VIN2 domain and the point of interaction between gp120 and T cells, with the 1st and 3rd highest scoring anti-HIV AMPs having the highest binding affinities. However, all 10 putative anti-HIV AMPs bind to the N-terminal domain of p24 with large surface interaction, rather than the C-terminal. Conclusion: The in silica approach has made it possible to construct computational models having high performances, and which enabled the identification of putative anti-HIV peptides from genome sequence scans. The in silica validation of these putative peptides through docking studies has shown that some of these AMPs may be involved in HIV/AIDS therapeutics and diagnostics. The molecular validation of these findings will be the way forward for the development of an early diagnostic tool and as a consequence initiate early treatment. This will prevent the invasion of the immune system by blocking the VIN2 domain and thus designing of a successful vaccine with broad neutralizing activity against this domain.