AIM The objective of this study is to determine factors that may contribute to hospital admissions in a cohort of medically insured South African patients in the era of HAART. METHODS This was a retrospective cohort of all HIV-positive adult and paediatric patients enrolled on a medical aid disease management programme in South Africa over a period of three years. Patient-specific demographic and clinical information were obtained from the medical aid records. Survival analysis was used to analyse time to first admission looking at admissions occurring after enrolment to the programme, during the study period of between 01 January 2006 and 31 December 2008. Only the right censored cases were included in the analyses. Descriptive analyses were conducted on the key prognostic factors. Variables that were significant in the univariate were considered in the multivariate Cox proportional hazards model. RESULTS A total of 8440 patients were included in the analysis. Half of these patients had at least one admission during the observation periods with 43.28% having had 2 or more admissions. The average admission rate was 2 admissions per patient over the 36 month observation period. Young children, adolescents and the very old (> 60 years) were significantly more likely to be admitted than the middle age groups, HR = 1.30 [95%CI 1.21 -1.40] p<0.01, 1.24 [95%CI 1.10 – 1.41] and 1.13 [95% CI 1.10 – 1.27] p<0.01 respectively. Low CD4 cell counts of < 200 cells/ µL were significantly associated with a higher likelihood of hospitalizations with hazard ratios even greater for CD4 cell counts of less than 100 cells/ µL, HR= 1.34 [95%CI 1.29 – 1.39], p<0.01. Cases were more likely to be admitted by a clinical haematologist or gynaecologist than by other specialist categories.HR =1.58 [95%CI 1.29 –1.94] and 1.17[95%CI 1.08 – 1.27] respectively with p<0.01. CONCLUSION Factors that are associated with hospital admissions in this private sector, medically insured population are a younger and older age, low CD4 cell counts and admission by a clinical haematologist and gynaecologist. These results suggest that disease management strategies should be intensified for the younger and older age groups. All HIV-positive patients should be closely monitored for CD4 deterioration so that treatment is initiated timeously. Routine haematological investigations should be recommended for all HIV-positive patients in order to pick up and treat haematological conditions before they result in a hospital admission. Evidence based guidelines, outlining the place of caesarian section deliveries in the HIV population, should be developed for use by gynaecologists specifically in the private sector. Copyright / Dissertation (MSc)--University of Pretoria, 2011. / Clinical Epidemiology / unrestricted

>Magister Scientiae - MSc / Background: Despite the effort of scientific research on HIV therapies and to reduce the rate of HIV infection, AIDS still 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 therapeutic 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 defence 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 modelling 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 highest affinity and having the correct orientation to the HIV -1 proteins gp 120 and p24 were selected for future work so as 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 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 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 Escores, molecules 1,3, 8 and 10 firmly binds the gp120 binding pocket at the VIN2 domain and at 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.

Globally an estimated 33.4 million people were living with HIV/AIDS by 2008 (UNAIDS, 2009a:7). One of the main challenges facing the Republic of South Africa (RSA) today is the HIV/AIDS epidemic (NSP, 2007:17). By mid-year 2011 an estimated 5.38 million people (10.6% of the total population) were living with HIV/AIDS in the RSA (Statistics South Africa, 2011:2). Currently South Africa has the largest number of people enrolled in the Highly Active Antiretroviral Treatment programme (HAART) in the world (WHO, 2008:59). The objective of this study was to determine retrospectively the medicine treatment patterns of HAART at a district hospital in the North West Province of South Africa. The study was conducted at Thusong hospital in the Ditsobotla sub-district of the North West Province of South Africa. A non-experimental, retrospective, cross-sectional, drug utilisation research methodology was used to obtain the data. The target population included patients of all ages who visited Thusong hospital pharmacy during the data collection period, which commenced on 01 February 2012 and ended on 31 March 2012. The data of three hundred and ninety nine (N=399) adult and one hundred and sixty one (N=161) paediatric patients on HAART were used. The adult female patients accounted for almost 70% (n=276, 69.17%) and the adult male patients for only 30% (n=123, 30.83%). The male paediatric patients represented just over 60% (n=97, 60.25%), whereas the female paediatric patients comprised less than 40% (n=64, 39.75%). The majority of adult patients were unmarried (n=323, 80.95%) and this group of patients were also the youngest group (μ=36.38 ± 8.98 years) on ARV treatment. Almost 86% (85.96%, n=343) of adult patients were registered as unemployed. Ninety two (n=92, 23.06%) adult patients and fifty eight (n=58, 36.03%) paediatric patients defaulted treatment during the defined period. The investigation into the adult medicine treatment patterns revealed that more than half (52.38%, n=209) of all the adult patients were receiving regimen 1atn (EFV, TDF and 3TC), followed by 20.80% (n=83) on regimen 1a (EFV, D4T and 3TC). Most paediatric patients (n=73, 45.34%) were on regimen P1c (EFV, D4T and 3TC) and the second most (n=45, 27.95%) were on regimen P1a (D4T, 3TC and LPV/r). The average weight of adult female patients was 57.18kg (± 15.78kg) and the average adult male patient weighed 55.87kg (± 10.17kg) on initiation of HAART. The average adult male patient was initiated on HAART with a CD4 count of 130cells/mm3 (± 99.45cells/mm3), while for adult female patients it was 160cells/mm3 (± 96.52cells/mm3). The average male child was initiated with a CD4 count of 509.1cells/mm3 and the average female paediatric patient with 477.3cells/mm3. The average viral load for adult female patients on initiation of HAART was 103046copies/mm3 (± 189146copies/mm3) and for adult male patients it was 416600copies/mm3 (± 439746copies/mm3). The difference between the viral load of adult female and male patients were described as statistically (p=0.0006) and practically (d=0.713) significant. The average viral load for female paediatric patients on initiation of HAART was 242207copies/mm3 (± 709133copies/mm3) and for male paediatric patients it was 329734copies/mm3 (± 674532copies/mm3). Adult patients that received HAART at more than 12 consultations revealed an average weight gain of 3.43kg (± 8.11kg) from initiation of treatment. This group also showed an average increase of 214.71cells/mm3 (± 248.24cells/mm3) in CD4 count and an average reduction in viral load of 170944copies/mm3 (± 191854.69copies/mm3) from the day they started HAART up to the last date of receiving treatment. The paediatric patients on treatment for more than 12 consultations showed an average weight gain of 6.56kg (± 3.75kg) from initiation of ARV treatmentup to the last date of receiving treatment. They also showed an average increase in CD4 count of 396.63cells/mm3 (± 594.53cells/mm3) and a very encouraging average decrease of 538369.37copies/mm3 (± 948634.46copies/mm3) in the viral load. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

Globally an estimated 33.4 million people were living with HIV/AIDS by 2008 (UNAIDS, 2009a:7). One of the main challenges facing the Republic of South Africa (RSA) today is the HIV/AIDS epidemic (NSP, 2007:17). By mid-year 2011 an estimated 5.38 million people (10.6% of the total population) were living with HIV/AIDS in the RSA (Statistics South Africa, 2011:2). Currently South Africa has the largest number of people enrolled in the Highly Active Antiretroviral Treatment programme (HAART) in the world (WHO, 2008:59). The objective of this study was to determine retrospectively the medicine treatment patterns of HAART at a district hospital in the North West Province of South Africa. The study was conducted at Thusong hospital in the Ditsobotla sub-district of the North West Province of South Africa. A non-experimental, retrospective, cross-sectional, drug utilisation research methodology was used to obtain the data. The target population included patients of all ages who visited Thusong hospital pharmacy during the data collection period, which commenced on 01 February 2012 and ended on 31 March 2012. The data of three hundred and ninety nine (N=399) adult and one hundred and sixty one (N=161) paediatric patients on HAART were used. The adult female patients accounted for almost 70% (n=276, 69.17%) and the adult male patients for only 30% (n=123, 30.83%). The male paediatric patients represented just over 60% (n=97, 60.25%), whereas the female paediatric patients comprised less than 40% (n=64, 39.75%). The majority of adult patients were unmarried (n=323, 80.95%) and this group of patients were also the youngest group (μ=36.38 ± 8.98 years) on ARV treatment. Almost 86% (85.96%, n=343) of adult patients were registered as unemployed. Ninety two (n=92, 23.06%) adult patients and fifty eight (n=58, 36.03%) paediatric patients defaulted treatment during the defined period. The investigation into the adult medicine treatment patterns revealed that more than half (52.38%, n=209) of all the adult patients were receiving regimen 1atn (EFV, TDF and 3TC), followed by 20.80% (n=83) on regimen 1a (EFV, D4T and 3TC). Most paediatric patients (n=73, 45.34%) were on regimen P1c (EFV, D4T and 3TC) and the second most (n=45, 27.95%) were on regimen P1a (D4T, 3TC and LPV/r). The average weight of adult female patients was 57.18kg (± 15.78kg) and the average adult male patient weighed 55.87kg (± 10.17kg) on initiation of HAART. The average adult male patient was initiated on HAART with a CD4 count of 130cells/mm3 (± 99.45cells/mm3), while for adult female patients it was 160cells/mm3 (± 96.52cells/mm3). The average male child was initiated with a CD4 count of 509.1cells/mm3 and the average female paediatric patient with 477.3cells/mm3. The average viral load for adult female patients on initiation of HAART was 103046copies/mm3 (± 189146copies/mm3) and for adult male patients it was 416600copies/mm3 (± 439746copies/mm3). The difference between the viral load of adult female and male patients were described as statistically (p=0.0006) and practically (d=0.713) significant. The average viral load for female paediatric patients on initiation of HAART was 242207copies/mm3 (± 709133copies/mm3) and for male paediatric patients it was 329734copies/mm3 (± 674532copies/mm3). Adult patients that received HAART at more than 12 consultations revealed an average weight gain of 3.43kg (± 8.11kg) from initiation of treatment. This group also showed an average increase of 214.71cells/mm3 (± 248.24cells/mm3) in CD4 count and an average reduction in viral load of 170944copies/mm3 (± 191854.69copies/mm3) from the day they started HAART up to the last date of receiving treatment. The paediatric patients on treatment for more than 12 consultations showed an average weight gain of 6.56kg (± 3.75kg) from initiation of ARV treatmentup to the last date of receiving treatment. They also showed an average increase in CD4 count of 396.63cells/mm3 (± 594.53cells/mm3) and a very encouraging average decrease of 538369.37copies/mm3 (± 948634.46copies/mm3) in the viral load. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

Immunologic monitoring is part of the standard care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunologic monitoring in Ethiopia. This study assessed the pattern of immunologic monitoring, immunologic response, level of immunologic treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. A total of 1,321 documents of patients reviewed revealed timely immunologic monitoring were inadequate. Despite overall adequate immunologic response, the prevalence of immunologic failure was 11.5% (n=147). Having WHO Stage III/IV of the disease and a higher CD4 (cluster differentiation 4) cell count at baseline were identified as risks for immunologic failure. These findings highlight the magnitude of the problem of immunologic failure. Prioritizing monitoring for high risk patients may help in effective utilisation of meager resources / Health Studies / M.A. (Public Health)

Immunologic monitoring is part of the standard care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunologic monitoring in Ethiopia. This study assessed the pattern of immunologic monitoring, immunologic response, level of immunologic treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. A total of 1,321 documents of patients reviewed revealed timely immunologic monitoring were inadequate. Despite overall adequate immunologic response, the prevalence of immunologic failure was 11.5% (n=147). Having WHO Stage III/IV of the disease and a higher CD4 (cluster differentiation 4) cell count at baseline were identified as risks for immunologic failure. These findings highlight the magnitude of the problem of immunologic failure. Prioritizing monitoring for high risk patients may help in effective utilisation of meager resources / Health Studies / M. A. (Public Health)

Introdução: O emprego da terapia antirretroviral (TARV) proporcionou dramático impacto na mortalidade por aids e aumento na sobrevida. Entretanto, esse panorama depende da manutenção de altas taxas de adesão ao tratamento medicamentoso. A relevância da adesão tem sido reconhecida pelo Programa Nacional de DST e Aids desde o final dos anos 1990. Em que pese o destaque que o plano propositivo do Programa tem dado para a questão, ainda não dispõe de estudo atualizado sobre o número e tipo das atividades que estão em curso nos serviços. Este estudo teve por objetivo descrever as atividades de adesão em curso nos serviços de HIV/aids do Estado de São Paulo. Métodos: Foi enviado um questionário semi-estruturado para todos os 179 ambulatórios de HIV/aids do Estado, com perguntas sobre o tipo de serviço, pessoas sob TARV, formas e frequências de avaliação de adesão, atividades desenvolvidas (individuais, coletivas e para grupos específicos) e parcerias com organizações não governamentais. Para testar associação entre variáveis categóricas utilizou-se o teste Qui-quadrado de Pearson ou os testes exato de Fisher ou teste da razão de verossimilhanças, no nível de significância de p<0,05. A análise de agrupamento foi utilizada para investigar cada uma das associações de cada resposta com as variáveis: tamanho do município, tipo e tamanho das clínicas. Resultados: 136 dos ambulatório (76%) responderam à pesquisa. Quase todos (96,3%) relataram incentivar a adesão na prática clínica, predominantemente nas consultas de médicos (94,1%) e enfermeiros (67,6%). A maioria (78,7%) relatou avaliar a adesão através de registros da farmácia. Grupos (38,2%) e palestras (28,7%) foram as atividades de grupo mais conduzidas. A análise de agrupamento identificou três grupos de ambulatórios, dois deles muito distintos. Grupo 1 (27 ambulatórios) foi composto predominantemente por unidades de saúde básica, com menos de 100 pacientes, apresentaram a menor freqüência de avaliação da adesão e menos atividades individuais e em grupo. Grupo 2 (51 ambulatórios) foi constituído principalmente por ambulatórios especializados em HIV/aids, com mais de 500 pacientes, com maior freqüência de avaliação da adesão, maior participação de psicólogos, assistentes sociais e farmacêuticos e mais atividades individuais e em grupo. Grupo 3 (56 ambulatórios) foi composto em sua maioria por ambulatórios de especialidades e de médio porte, com a maioria das atividades semelhantes ao Grupo 2, exceto pela ausência de atividades para grupos específicos e menos envolvimento multidisciplinar. Conclusão: Dado o amplo reconhecimento da importância da adesão por parte das clínicas, ainda há poucas atividades específicas de adesão no Estado. As clínicas maiores e mais especializadas tendem a oferecer mais atividades individuais e em grupo, utilizando abordagens multidisciplinares. Maior atenção deve ser dada para a descentralização do atendimento às pessoas vivendo com HIV para assegurar cuidados de qualidade mais homogêneos em toda a rede ambulatorial. / Introduction: The use of antiretroviral therapy (HAART) has provided dramatic impact on AIDS mortality and improved survival. However, this scenario depends on maintaining high rates of adherence to HAART. The relevance of adherence has been recognized by the National STD/AIDS Program since the late 1990s. Despite the emphasis that the Program has given to the issue, there have been no study to date on the number and type of activities that are underway in the services. This study aimed to describe the HAART adherence support activities in Sao Paulo State HIV/AIDS clinics. Methods: We sent a semi structured questionnaire to all 179 HIV/AIDS clinics with questions about type of clinic, people on HAART, adherence assessment, activities (individual, group and for specific groups). To test association between categorical variables used the chi-square test or Fisher exact test or likelihood ratio test at a significance level of p <0.05. Cluster analysis was used to investigate each association of each answer with the variables: municipality size, type and size of the clinics. Results: 136 clinics (76%) answered the survey. Almost all (96.3%) reported encouraging adherence in clinical practice, particularly in the medical (94.1%) and nurse (67.6%) visits. Most (78,7%), reported assessing adherence by pharmaceutical records. Groups (38.2%) and lectures (28.7%) were the group activities most developed. Cluster analysis identified three groups of clinics; two of them were too different. Group 1 (27 clinics) was predominately composed by primary care clinics, with less than 100 patients, the lowest frequency of assessing adherence and fewer individual and group activities. Group 2 (51 clinics) predominately composed by HIV specialized clinics specializing, HIV/AIDS, with more than 500 patients, assessing adherence more frequently, with greater involvement of psychologists, social workers and pharmacists developing more individual and group activities. Group 3 (56 clinics) was predominately composed by medium size specialized clinics, with majority of activities similar to Group 2, except by the absence of activities to specific groups and less multidisciplinary involvement. Conclusion: Given the broad recognition of the adherence importance by the clinics, there are still few specific adherence activities. The larger and more specialized clinics tend to provide more individual and group activities, using multidisciplinary approaches. Greater attention should be given to the decentralization of care offered to people living with HIV to ensure more homogeneous quality care across the ambulatory network.

HIV (Human Immunodeficiency Virus) has been shown to have significant effects on the development of a child. Currently there is limited South African research regarding HIV and specific characteristics of communication development, and the treatment thereof, in the child infected with HIV. The objective of the research was to describe the communication characteristics of a group of children between the ages of 0 – 5 years infected with HIV at a hospital in Gauteng, South Africa. Clinic records of 203 children infected with HIV between the ages of 0-5 years were reviewed by using a pre-designed checklist within the outreach clinic of a large regional hospital. A questionnaire was completed by 4 medical practitioners working with this population within the outreach clinic. A total of 91.62% of the infected children were diagnosed as being either in Stage III or IV of the disease (according to the WHO classification system of 2005), with all infants presenting with a CD4 count of ≤ 60. The majority (75.37% of the total sample) were receiving HAART (Highly Active Antiretroviral Therapy) at the time the data was collected. According to their medical, social, communication and general development, almost all the children qualified for Early Communication Intervention (ECI) but were not recorded as being referred for such services. A large proportion of the target population presented with opportunistic infections and/or HIV associated conditions. The results highlight the developmental characteristics of children living with HIV, and identify the need for medical doctors and allied health professionals to be provided with relevant literature or training regarding the communication development of children infected with HIV. This will facilitate appropriate referrals for ECI services.

L’épidémie du VIH a bouleversé le rapport de la médecine à l’individu et inversement. D’une part, la forte stigmatisation associée à la contamination par le virus a rendu le vécu de la maladie plus complexe que pour toute autre pathologie. D’autre part, la chronicisation de l’infection impliquant une prise en charge complexe à base d’une multithérapie au long cours a contraint les soignants à s’interroger plus en profondeur sur la relation intime du patient à son traitement, et tout particulièrement sur l’observance thérapeutique. L’idée de ce travail de thèse est de poursuivre une argumentation en faveur d’une nouvelle approche moins paternaliste de l’observance aux antirétroviraux, incluant un partage des savoirs entre le médecin et le patient, et de l’appliquer à des populations de patients dont les comorbidités compliquent la prise en charge telles que la dépendance aux opiacés et l’infection par le virus de l’hépatite C. A travers une série d’articles, nous avons montré que la prise en compte de la perception du patient vis-à-vis des soins permettait de mieux comprendre la non-observance aux traitements. Chez les personnes traitées pour leur dépendance, la non-observance peut être définie comme l’injection du traitement de substitution ou la consommation d’opiacés illicites. La diminution ou l’arrêt de ces pratiques est un processus long, souvent ponctué de rechutes et elles peuvent être le reflet d’une prise en charge inadaptée. Les résultats de ce travail ont permis de mettre en évidence l’effet positif d’un accès à des soins adaptés, à travers une prise en charge de la pathologie mais aussi la réduction des risques liés à la non-observance. Il s’agit là de promouvoir une relation plus délibérative entre le médecin et le patient. / The epidemic of Human Immunodeficiency Virus (HIV) has profoundly changed the relationship between medicine and humans and vice versa. On the one hand, the intense stigmatization associated with HIV infection has made the disease more complex than for any other pathology. On the other hand, the chronicization of infection has forced care providers to investigate in greater detail the intimate relationship between patient and treatment, and more particularly, the therapeutic adherence. My research work aimed to investigate this latter argument in greater detail, favoring a less paternalistic approach toward therapeutic adherence in HIV-infected patients and applying this approach to multi-treated populations with comorbidities such as drug dependence and hepatitis C. Through several articles, we tried to put in evidence that a model of care that includes patient’s perception about care may lead to better understand non-adherence to treatment (ongoing drug use, drug injection or treatment diversion). In fact, injection cessation or reduction of opioid consumption in dependent individuals is a non-linear process which could take a long time, and which is often punctuated with relapse. Our findings showed the positive impact of access to adequate care to treat not only the disease but also the harm related to non adherence to treatment. The idea is to promote a more deliberative relationship between physician and patient, including a harm reduction approach.

Étant donnée la séquence hautement conservée de la NC et son rôle crucial dans le cycle viral de VIH-1, les molécules inhibant la NC sont susceptibles d'agir comme complément aux thérapies anti-rétrovirales à haute activité (HAART) basées sur des médicaments ciblant les enzymes virales, Des médicaments anti-NC sont ainsi susceptibles d'entraîner un maintien de l'inhibition de la réplication d'un large panel d'isolats VIH-1 incluant des lignées virales résistantes aux médicaments ciblant les enzymes virales. Récemment, dans le cadre du consortium Européen TRIoH, de nouvelles stratégies visant à cibler spécifiquement les propriétés chaperonnes de la NC sur les acides nucléiques ont été développées. Selon une stratégie protégée par un brevet soumis, une série de peptides a été conçue afin d'agir comme compétiteurs de la NC et pouyant ainsi inhiber la réplication du virus. Au sein de cette série, plusieurs peptides ont montré une inhibition efficace des propriétés de déstabilisation des acides nucléiques par la NC. Quatre de ces peptides ont été testés en milieu cellulaire et trois d'entre eux ont montré qu'ils pouvaient inhiber efficacement la réplication du HIV-1 dans les lymphocytes. Dans ce contexte, un premier objectif de cette thèse fût de caractériser avec précision les propriétés de ces peptides. En outre, un objectif supplémentaire fût de caractériser le mécanisme moléculaire vis-à-vis de la NC de petites molécules anti-virales développées par les groupes de D. Daelemans (Leuven) et M. Botta (Sienne).