Orientador: Marcos Tadeu Nolasco da Silva / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T13:32:12Z (GMT). No. of bitstreams: 1 Ramalho_LuizCarlosdeBarros_M.pdf: 6621939 bytes, checksum: becaf1c06f630ae4ad79ba5cca85c06c (MD5) Previous issue date: 2010 / Resumo: Introdução: Desde o início da pandemia, acumulam-se evidências que demonstram a estreita relação da desnutrição com a Aids. Entre as consequências da desnutrição na criança com Aids, destacam-se o baixo peso e a baixa estatura. Estudos apontam que a introdução da Terapia Antirretroviral Potente (TARV) tem prolongado a vida e tem proporcionado redução de doenças oportunísticas em pacientes pediátricos infectados pelo HIV. Por outro lado, em consequência do tratamento, durante um longo período de uso, tem sido identificada uma variedade de efeitos colaterais adversos, como a lipodistrofia e lipohipertrofia. Objetivo: Avaliar o estado nutricional e a composição corporal em crianças brasileiras infectadas pelo HIV, bem como a associação de tais variáveis com aspectos clínicos, imunológicos, virológicos, terapêuticos e de estilo de vida. Método: Estudo tipo corte transversal, em que foram avaliadas 94 crianças infectadas pelo HIV e 364 saudáveis. A composição corporal foi mensurada por variáveis antropométricas, como peso, altura, Índice de Massa Corporal (IMC) e pregas cutâneas. Identificou-se a gordura truncal por meio da razão das dobras cutâneas subescapular/tricipital (DCSE/DCTR) e o acúmulo de gordura na região abdominal pela circunferência da cintura e relação cintura quadril (RCQ). A Lipodistrofia foi identificada na avaliação clínica. As categorias clínicas e imunológicas foram definidas por critérios do Ministério da Saúde do Brasil. Empregou-se recordatório alimentar de 24 horas para avaliar a dieta e questionários (IPAQ-C e PAQ-C) para Atividade Física. Para análise estatística, utilizou-se o programa "SPSS for Windows". Resultados: Encontrou-se prevalência de baixa estatura em 25,53%, desnutrição em 22,34%, lipodistrofia em 38,29%, e lipohipertrofia em 40,42% dos pacientes; observou-se associação do percentual de gordura corporal maior (p < 0,001) no sexo feminino. A DCSE/DCTR esteve associada com a idade (p = 0,021) e mostrou-se maior no sexo masculino (p = 0,016). A RCQ associou-se com a idade (p=0,003) e com a categoria imunológica 3 (p=0,004). A circunferência da cintura associou-se com a idade (p < 0,001). O uso de IP atual esteve associado com desnutrição (OR 3,51, IC 1,07-11,44) e lipoatrofia (OR 3,5, IC 1,37-8,95), a categoria imunológica 3 revela maior risco de lipohipertrofia (OR 2,5, IC 1,06 - 5,91) e a categoria clínica C apresentou maior risco de baixa estatura (OR 3,68 - IC 1,39 - 9,73). Ao comparar o sexo feminino entre grupos, HIV e Controle, a RCQ e circunferência da cintura foram maiores nas meninas infectadas pelo HIV (p < 0,001) e (p=0,011), respectivamente A DCSE/DCTR esteve mais elevada no grupo controle (p= 0002). Ao comparar os indivíduos infectados pelo HIV com o grupo controle, os pacientes apresentaram maior risco de baixa estatura (OR 5,33, IC 2,83 - 10,04), desnutrição (OR 4,7, IC 2,44 - 9,06) e menor risco de obesidade e sobrepeso (OR 0,33, IC 0,14 - 0,78). Conclusão: O grupo de crianças infectadas pelo HIV, em TARV, possui maior acometimento no estado nutricional e na composição corporal e suas alterações corporais foram associadas ao uso de IP atual. Tais alterações são consistentes com a gravidade e cronicidade da infecção por transmissão vertical e com as consequências da TARV prolongada / Abstract: Background: Since the beginning of the pandemic, there is mounting evidence demonstrating the close relationship between Aids and malnutrition. The consequences of malnutrition in Aids children include low weight for age and short stature. Studies indicate that the introduction of Highly Active Antiretroviral Therapy (HAART) has prolonged life and proportionated the reduction of opportunistic diseases in pediatric HIV- infected patients. However, as a result of chronic therapy, a variety of adverse effects, such as lipodystrophy and lipohypertrophy, has been identified. Objective: To assess nutritional status and body composition in HIV-infected Brazilian children, and the association of these variables with clinical, immunological, virological, therapeutic and lifestyle variables. Methods: A cross-sectional study, which evaluated 94 HIV-infected and 364 healthy hildren. Body composition was measured by anthropometric variables such as weight, height, body mass index (BMI) and skin folds. Truncal fat was identified by the ratio of subscapular / triceps skinfolds (DCSE / DCTR) and the accumulation of abdominal fat by waist circumference and waist-hip ratio (WHR). Lipodystrophy was identified in clinical evaluation. Clinical and immunological categories were defined by criteria of the Ministry of Health of Brazil. We applied 24 hour-food recall to assess the diet and questionnaires (IPAQ-C and PAQ-C) for Physical Activity. SPSS for Windows software was used for statistical analysis. Results: Stunting was identified in 25.53% of the patient group, malnutrition in 22.34%, lipodystrophy in 38.29%, and lipohypertrophy in 40.42% of patients. HIV-infected girls showed significantly greater body fat percentage (p <0.001). The DCSE / DCTR was associated with age (p = 0.021) and was higher in males (p = 0.016). WHR was associated with age (p = 0.003) and with immunologic category 3 (p = 0.004). Waist circumference was associated with age (p <0.001). Current IP usage was associated with malnutrition (OR 3.51, CI 1,07-11,44) and lipoatrophy (OR 3.5, CI 1,37-8,95), the immunologic category 3 was associated with lipohypertrophy (OR 2.5, CI 1.06 to 5.91) and clinical category C with greater risk of stunting (OR 3.68 - CI 1.39 to 9.73). When comparing the groups among females, HIV and Control, WHR and waist circumference were higher in HIV-infected females (p <0.001 and p = 0.011, respectively). The DCSE / DCTR ratio was higher in the control group (p = 0002). When compared to the control group, patients had higher risk of stunting (OR 5.33, CI 2.83 to 10.04), malnutrition (OR 4.7, CI 2.44 to 9, 06) and lower risk of obesity and overweight (OR 0.33, CI 0.14 to 0.78) .Conclusion: The group of HIV-infected children on HAART showed significant nutritional status and body composition abnormalities, and body composition changes were associated with the use of current PI. These changes are consistent with the severity and chronicity of infection by vertical transmission of HIV and the consequences of prolonged HAART / Mestrado / Saude da Criança e do Adolescente / Mestre em Saude da Criança e do Adolescente

Magister Public Health - MPH / According to the Demographic and Health Survey in Zambia the national HIV prevalence among population aged 15-49 years was 14%. In 2002 the Government of Zambia introduced Antiretroviral Therapy (ART) in two of the largest hospitals in Zambia: Lusaka and Ndola hospitals. As many people begin accessing ART in rural areas in Zambia, one of the major challenges is ensuring that those receiving ART adhere to treatment to avoid the emergence of drug resistance and treatment failure. The research therefore set to identify the potential barriers and facilitators to antiretroviral treatment adherence among people living with HIV and AIDS in the rural district of Chongwe,Zambia.A descriptive qualitative study was conducted over a period of three weeks from 11th December to 29th December 2008. The perceptions, opinions and experiences of PLHIV on ART and those of the health workers and treatment supporters were explored through in-depth interviews and focus group discussions. In-depth interviews were conducted with nine persons living with HIV (PLHIV): 5 females and 4 males. Two focus group discussions were conducted with members of 2 different PLHIV support groups from Refunsa and Chimusanya villages served by the ART clinic of St Luke Mission Hospital and another with a group of ART treatment supporters. In addition, interviews were held with five key informants, who were health workers from the ART clinic in St Luke Mission Hospital in Mpanshaya.Reported barriers to adherence among PLHIV in rural areas included experiencing side effects to ART drugs, stopping medication due to improvement in wellbeing, a lack of understanding of the importance of adherence, and forgetting to take their medication due to alcohol consumption. Other barriers included stigma and discrimination, inadequate food to support ART uptake and non disclosure of one’s status for fear of being rejected especially for women who feared rejection in relationships. Another key barrier to adherence was the religious belief held by some PLHIV that one would get healed after being prayed for and therefore discontinued treatment.Key facilitators to adherence identified in the study included getting into a regular routine of taking antiretroviral drugs (ARVs), knowledge of and belief in the efficacy of ART, disclosure of HIV status, access to social support and nutritional support. Other facilitators identified were use of treatment supporters who provided support to PLHIV by providing them with on-going adherence counseling, and making referrals to the ART facility for further support, mobile ART clinics that have brought ART services closer to the rural communities and the adaptation of strategies such as clocks and use of alarms by PLHIV to remind them to take their medication. Although better health resulting from taking ARVs was citied as a barrier to adherence it also acted as a facilitator to adherence as better health motivated PLHIV to continue taking their medication.In conclusion, based on the findings from the study a series of recommendations were made to inform the current ART adherence information and counseling strategies used by the ART facility at St Luke Mission Hospital in Mpanshaya - and other ART programmes being implemented in similar rural health facilities in Zambia. The recommendations included the need for the ART facility to address alcohol abuse among PLHIV taking ART, addressing perceptions on ARVs in the community, reviewing of the counseling programme, caring for treatment supporters, strengthening food security and livelihood opportunities for PLHIV and their families and increasing collaboration between the ART facility and the churches.

Bakgrund. En effektiv behandling för hiv kom år 1996. Behandlingen för hiv kan orsaka en rad biverkningar som skulle kunna påverka följsamheten. Minskad följsamhet har lett till läkemedelsresistens. Syfte. Syftet är att undersöka upplevelser av följsamhet hos personer som lever med hiv under antiretroviral tablettbehandling (ART). Metod. En litteraturstudie med kvalitativ ansats. Resultat. 12 vetenskapliga artiklar ligger till grund för litteraturstudiens resultat. Majoriteten av personer som lever med hiv (PLH) hittade egna strategier för att hitta motivation till att uppnå följsamhet. Depressiva symtom och substansberoende var i flertalet fall en hindrande faktor för PLH:s följsamhet. PLH:s omgivning och nätverk var både en motverkande faktor och en hjälpsam faktor för PLH:s följsamhet. För PLH, som inte hade råd med mat eller som hade en instabil levnadssituation, upplevde svårigheter med att uppnå följsamhet. Hur PLH kände sig bemötta av vårdgivare påverkade följsamheten. För PLH var det viktigt för PLH att känna sig delaktiga i sin vård gällande ART och biverkningar. Hjälpmedel och patientutbildning var verktyg som kunde underlätta för PLH att uppnå följsamhet. Rutiner visade sig vara väsentligt för PLH att uppnå följsamhet. Slutligen var biverkningar till följd av ART en hindrande faktor för att uppnå följsamhet. Konklusion. Biverkningar, samsjuklighet med psykisk ohälsa samt stigma var de främsta faktorerna som hindrade PLH att uppnå följsamhet. Vidare kunskapsutveckling behövs för att minska biverkningar, behandla samsjuklighet och motarbeta stigmatisering för att PLH lättare ska upprätthålla följsamheten. Endel av kunskapsutvecklingen är att den grundutbildade sjuksköterskan behöver bredare kunskap. / Background. The effective treatment for HIV was available in 1996. The treatment for HIV causes several side effects that could have an impact on adherence. Low adherence has led to medical resistance. Aim. The aim is to explore experiences of adherence by people living with HIV with ongoing antiretroviral pill treatment (ART). Method. A literature study with a qualitative approach. Result. This study is based on 12 scientific articles. The majority of people living with HIV (PLH) discovered their own strategies to find motivation in being adherent. Depressed mood and substance addiction were a hindering factor in being adherent. The network and surrounding of PLH were either a discouraging or facilitating factor to adherence. PLH with food insecurity and homelessness experienced difficulties adhering to ART. Clinicians approach to PLH influenced the rate of adherence. It was essential that PLH was involved in their own care regarding ART and side effects. Utilities and patient education were useful tools to facilitate adherence. Routines were shown to be essential for PLH in being adherent. Lastly, side effects due to ART were a hindering factor in achieving adherence. Conclusion. Side effects, comorbidity with mental illness and stigma were the main factors hindering PLH in achieving adherence. Further research is needed to reduce side effects, treat comorbidity and counteract stigma to facilitate adherence. The further research is needed to broaden the knowledge of registered nurses.

Thesis (MScMedSc (Pathology. Medical Virology))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: In 2007, AIDS caused an estimated 2.1 millions deaths worldwide; about 70% in sub-Saharan Africa. HIV preferentially targets activated CD4 T cells, expressing the major HIV receptor CD4, as well as the major chemokine coreceptors CCR5 and CXCR4. These coreceptors play a prominent role during HIV cell entrance phase, HIV transmission and also disease progression. They have been found to be differentially expressed by CD4 T cell subsets. Tuberculosis coinfection may enhance immune activation in vivo thus accelerating HIV disease progression and has become a major challenge in the control of TB in Africa. Introduction of HAART has reduced disease progression to AIDS, as well as risk of further morbidity and mortality. HAART results in a rapid decline of viral load and an initial increase of peripheral CD4 count, however little is known on the effect of HAART in regulation of coreceptor expression, immune activation status and CD4 T cell subset distribution in HIV infection and HIV/TB coinfection. This study is a cross-sectional analysis of coreceptor expression, immune activation status and CD4 T cell subpopulation distribution in South African HIV and HIV/TB coinfected patients before and after ARV. A total of 137 South African individuals were investigated, comprising 15 healthy normal donors (healthy subgroup), 10 patients with active pulmonary tuberculosis (PTB subgroup), 33 HIV-1 positive patients without active PTB (HIV subgroup), 23 positive patients with active PTB (HIV/PTB subgroup), 36 HIV-1 positive patients on ARV (HIV on ARV subgroup) and 20 HIV-1 positive patients with active PTB on ARV (HIV/PTB on ARV subgroup). CD4 absolute count and plasma viral load were determined for all donors. Freshly isolated PBMC were classified by flow cytometry into the following CD4+ T lymphocyte subsets: naïve (CD45+, CD27+), effector memory (CD45-, CD27-), central memory (CD45-, CD27+), and effector (CD45+, CD27-). Coreceptor expression and activation status was assessed by CCR5, CXCR4 and CD38 expression on CD4 T cell subsets. HIV, TB and HIV/TB coinfection was associated with a decrease in percentage CCR5+ T cells as compared to healthy controls, with the HIV/TB group showing the most extensive decrease. In treatment naive patients, CD4 T cells showed elevated surface expression of CCR5 and CD38 as determined by mean fluorescence intensity in HIV/TB co-infection compared to HIV infection alone. The percentage of antigen-experienced cells was higher in the HIV/TB co-infected group compared to the HIV group. The percentage of naïve T cells was decreased in both the HIV infected and the HIV/TB co-infected groups compared to healthy controls. HIV patients with more than 6 months of ARV showed decreased CCR5 and CD38 surface level expression in the HIV and the HIV/ TB co-infected subgroups. An increased percentage of naïve T cells was observed in the HIV infected subgroup, but not in the HIV/TB subgroup, similarly, a decreased percentage of antigen-experienced cells was observed in the HIV subgroup, but not in the HIV/TB co-infected subgroup. A positive correlation was found between CCR5 and CD38 expression, and CXCR4 and CD38 expression (Spearman coefficient of correlation respectively: r=0.59, p<0.001 and r=0.55, p<0.001). Furthermore we found plasma viral load positively associated with CD38 expression (r=0.31, p<0.001) and percentage activated CCR5+ expressing CD4 T cells positively related to viral load (r=0.31, p<0.001). Percentage naïve CD4 T cells was positively associated with CD4 count (r=0.60, p<0.001) and negatively correlated to viral load (r=-0.42, p<0.001). These results indicate that TB coinfection exacerbates certain aspects of dysregulation of CD4 T cell homeostasis and activation caused by HIV infection. In addition, ARV-associated decrease in coreceptor expression, immune activation status and a normalisation of CD4 T cell subset distribution was observed in HIV infected individuals, but not in HIV/TB coinfection. Despite viral suppression after ARV treatment, the decline in the immune activation marker CD38 and coreceptor CCR5 expression, increase in percentage naïve CD4 T cells and decrease of antigen-experienced cells did not reach the levels displayed in the healthy control group. This may indicate that ongoing (albeit reduced) T cell immune activation may occur in the presence of ARV. Further longitudinal studies are needed to closely monitor immune activation during ARV treatment. This study highlighted an association of TB disease with immune activation in HIV infection, the importance of T-cell activation in HIV pathogenesis and its impact on ARV treatment. Further studies are needed to identify causative factors that may lead to a persistent immune activation status during ARV treatment, and how TB coinfection confounds normal responses to ARV. / AFRIKAANSE OPSOMMING: In 2007 was ongeveer 2.1 miljoen sterftes wêreldwyd veroorsaak deur VIGS; ongeveer 70% in Sub-Sahara Afrika. CD4 T selle is die hoof teiken van MIV, aangesien dit die primêre CD4 reseptor, sowel as een of beide van die vernaamste chemokien koreseptore CCR5 en CXCR4 vrystel. Hierdie koreseptore speel ‘n prominente rol wanneer die MIV die sel binnedring, asook tydens MIV oordrag en verloop van die siekte. Dit word ook deur verskillende fraksies van CD4 T selle vrygestel. Gelyktydige TB infeksie mag immuunaktivering in vivo verhoog en dus die siekeproses versnel. MIV het ‘n groot uitdaging geword in die beheer van TB in Afrika. Bekendstelling van HAART het die ontwikkeling van VIGS vertraag, asook die risiko van verdere morbiditeit en mortaliteit. HAART veroorsaak ‘n vinnige afname in virale lading ‘n toename in CD4 telling, hoewel die spesifieke invloed van HAART op die regulering van koreseptor vrystelling, immuunaktivering en verspreiding van CD4 fraksies in MIV en MIV/TB infeksies nog onduidelik is. Hierdie studie het gepoog om koreseptor vrystelling, immuunaktiveringstatus en die verspreiding van CD4 subpopulasies in pasiënte met MIV en MIV/TB voor en na ARV behandeling te ondersoek. ‘n Totaal van 137 Suid-Afrikaanse individue is ondersoek en die studiegroep het bestaan uit 15 normale persone (gesonde subgroep), 10 pasiënte met aktiewe pulmonale TB (PTB subgroup), 33 MIV positiewe pasiënte sonder PTB (MIV subgroep), 23 MIV positiewe pasiënte met aktiewe PTB (MIV/PTB subgroep), 36 MIV positiewe pasiënte op ARV (MIV op ARV subgroep) en 20 MIV positiewe pasiënte met aktiewe PTB op ARV (MIV/PTB op ARV subgroep). Absolute CD4 telling en virale ladings was bepaal vir alle deelnemers. Vars geïsoleerde perifere bloed mononukleêre selle is geklassifiseer deur middel van vloeisitometrie as die volgende CD4 T limfosiet subgroepe: naïewe selle (CD45+, CD27+), effektor geheueselle (CD45-, CD27-), sentrale geheueselle (CD45-, CD27+), en effektor selle (CD45+, CD27-). Koreseptor vrystelling en aktivering was beoordeel volgens CCR5, CXCR4 en CD38 vrystelling op CD4 T sel subgroepe. HIV, TB en MIV/TB ko-infeksie is geassosieer met ‘n afname in die persentasie CCR5+ T selle, vergeleke met gesonde kontroles, waar die MIV/TB subgroep die grootste afname getoon het. In onbehandelde pasiënte het die CD4 T selle verhoogde vrystelling van CCR5 en CD38 op die oppervlakte getoon en dit is bevestig deur die gemiddelde fluoresserende vii intensiteit in die MIV/TB subgroep vergeleke met die subgroep met slegs MIV. Die MIV/TB subgroep het verder ook ‘n verhoogde persentasie totale geheue T selle getoon vergeleke met die MIV subgroep. Die persentasie naïewe T selle was egter verlaag in beide die MIV en MIV/TB subgroepe vergeleke met normale kontroles. MIV pasiënte wat langer as 6 maande op ARV behandeling was in beide die MIV en MIV/TB subgroepe, het ‘n verlaagde vrystelling van CCR5 en CD38 op die oppervlakte van die CD4 selle getoon. ‘n Verhoogde persentasie naïewe T selle het in die MIV subgroep voorgekom, maar nie in die MIV/TB subgroup nie. ‘n Soortgelyke tendens is gevind waar die persentasie totale geheueselle verlaag was in die MIV subgroep, maar nie in die MIV/TB subgroep nie. ‘n Positiewe korrelasie is gevind tussen CCR5 en CD38 vrystelling, asook CXCR4 en CD38 vrystelling (Spearman korrelasie koëffisiënt: r=0.59, p<0.001 en r=0.55, p<0.001 onderskeidelik). Verder het die plasma virale lading ‘n positiewe assosiasie getoon met CD38 vrystelling (r=0.31, p<0.001) en die persentasie geaktiveerde CCR5+ vrystellende CD4 T selle met virale lading (r=0.31, p<0.001). Die persentasie naïewe CD4 T selle het ‘n positiewe assosiasie getoon met CD4 telling (r=0.60, p<0.001) en ‘n negatiewe korrelasie met virale lading (r=-0.42, p<0.001). Volgens hierdie resultate vererger TB ko-infeksie sekere aspekte van die disregulasie van CD4 T selhomeostase en aktivering as gevolg van MIV infeksie. Verder kon ‘n ARVgeassosieerde afname in koreseptor vrystelling, immuunaktivering en normalisering van CD4 T sel fraksies bespeur word in die MIV subgroep, maar nie in die MIV/TB subgroep nie. Ten spyte van virale onderdrukking veroorsaak deur ARV behandeling, het die afname in die immuunmerker CD38 en koreseptor CCR5, toename in die persentasie naïewe CD4 selle en afname in totale geheue CD4 T selle nie die vlakke van die normale kontrolegroep bereik nie. Dit is moontlik dat volgehoue verlaagde T sel immuunaktivering nog steeds mag plaasvind in die teenwoordigheid van ARV. Verdere longitudinale studies is nodig om immuunaktivering tydens ARV behandeling te monitor. Hierdie studie het die belangrikheid van T sel aktivering in MIV patogenese en dit impak daarvan op ARV behandeling beklemtoon. Verdere studies is nodig om moontlike oorsake of bydraende faktore te identifiseer wat tot volgehoue immuunaktivering tydens ARV behandeling kan lei, asook tot mate waartoe TB ko-infeksie kan inmeng met die normale werking van ARV behandeling.

Thesis (MScMedSc)--University of Stellenbosch, 2011. / It is estimated that 32.8 million people are living with Human Immunodeficiency Virus (HIV) globally with the number of people receiving antiretroviral therapy in low- and middle- income counties increasing to more than 5 million people in 2009. These successes are threatened by treatment failure and the development of resistance to treatment. With an estimated 3.7% patients failing first line treatment after 2 years and 17.9% after 4 years on treatment there is a need for a practical and cheap in-house drug resistance assay that can be used to provide drug resistance data to clinicians and to use as a research tool to investigate drug resistance. In this study we attempted to optimize and validate an in-house drug resistance assay, adapted from Jacobs et al, 2008, to be used as a diagnostic tool and to study the presence of antiretroviral resistance in patients on the Western Cape Mother-To-Child-Transmission (MTCT) regimen. Quality control samples were received from The National Institute of Communicable Diseases AIDS Virus Research Unit, The Round Robin HIV-1 genotyping assessment system from the University of Würzburg and the QCMD assessment system were used for the optimization and validation of an in-house drug resistance assay. The ViroSeq™ HIV-1 Genotyping System was used for comparison of sample and mutation detection. It was possible to optimise and validate a genotyping assay for diagnostic testing and research use by comparison with the ViroSeq™ HIV-1 Genotyping System and evaluation with external quality assessment systems. This assay could subsequently be used to determine the development of genotypic-antiretroviral resistance in patients treated according to the provincial prevention of mother-to-child-transmission (PMTCT) protocol in the Western Cape (single dose nevirapine (sd-NVP), combined with a short course Zidovudine (AZT)). Patient samples were collected from pregnant women who took part in the Western Cape PMTCT program and visited the Tygerberg Obstetrics Clinic and Delft Community Hospital. EDTA blood was obtained to measure CD4-cell count, viral load, and to do genotyping for viral subtype and the presence of resistance mutations. Information on prior exposure to antiretroviral therapy was also collected. A detected resistance rate of 17.1% in this predominantly HIV-1 subtype C population is lower than previously recorded when sd-NVP was administered to HIV-1 subtype C positive patients in PMTCT programs. This could indicate that a dual PMTCT regimen including AZT and NVP reduces the risk of resistance to NVP relative to a regimen that uses sd-NVP. The genotyping assay uses four primers to amplify the PR and the RT gene separately to obtain PCR products, of 487 and 804 base pairs respectively for sequencing. The two PCR products were sequenced with three and five primers respectively to sequence the complete PR and approximately 250 amino acids of the RT gene. The sequences generated, thus, are analysed and aligned with the Sequencer V4.7 software to obtain a consensus sequence of approximately 1200 base pairs for analysis of resistance mutations in the protease and reverse transcriptase genes. The developed assay was hence further simplified and improved, by combining the PR and RT assay into one, which was optimised and validated for use in the routine diagnostic setting. The final genotyping assay uses 8 primers for sequencing to obtain a 1200 bp sequence for genotyping that contains the protease and the 5’ of the reverse transcriptase genes in which antiretroviral resistance associated mutations are found. The assay was accredited by SANAS in 2008.

Ce travail de thèse avait pour objectif d’évaluer l’accessibilité, l’efficacité et les difficultés opérationnelles de la prise en charge antirétrovirale précoce des enfants infectés par le VIH en Afrique de l’Ouest : en Côte d’Ivoire, au Mali et au Burkina Faso. Cette région est particulièrement marquée par un faible accès à la prise en charge des enfants infectés par le VIH. Nos travaux ont montré qu’à coté de l’offre de soins qui est insuffisante dans cette région, le retard aux soins chez ces enfants était particulièrement influencé par la faible acceptabilité parentale du dépistage pédiatrique précoce, avec un rôle clé du père dans la décision de soins de l’enfant. Les enfants débutent le traitement antirétroviral très tardivement, à un stade très avancé de la maladie et sévèrement immunodéprimé. Après douze mois de traitement antirétroviral, on observe un échec clinique ou immunologique au traitement chez plus de la moitié des enfants, en particulier chez ceux qui avaient débuté le traitement antirétroviral avec un mauvais état clinique et immunologique. Après cinq ans de traitement, près de la moitié des enfants présentent un échec virologique. Les interventions de prévention de la transmission mère-enfant ne semblent pas associées à l’échec au traitement des enfants dans cette région. Toutefois, l’observance au traitement antirétroviral chez le jeune enfant est bonne dans cette région. Ces résultats sont en faveur de la nécessité d’une prise en charge précoce des enfants infectés par le VIH, à un stade moins avancé de la maladie. Cela passe nécessairement par l’amélioration du dépistage pédiatrique précoce, à travers l’implication des pères, le renforcement du plateau technique pour le dépistage et le suivi des enfants, et la formation du personnel soignant. Aussi, les études de cohorte sur les facteurs pronostiques de l’échec au traitement dans le contexte opérationnel ouest africain sont nécessaires pour approfondir la question de la réponse au traitement antirétroviral chez ces enfants. / This thesis aimed to assess the accessibility, the efficiency and operational difficulties of treatment and care of HIV infected children in West Africa: Cote d’Ivoire, Mali and Burkina Faso. This region is particularly marked by poor access to care for HIV infected children. Our work has show that besides the insufficient provision of care in this region, the delay to care for these children was particularly influenced by the low acceptability of HIV early infant diagnosis, with a key role of the father in the decision making for the care of the child. Children begin antiretroviral treatment very late, at a very advanced stage of disease and severely immunocompromised. After twelve months of antiretroviral therapy, there was a clinical or immunological treatment failure in more than half of all children, especially among those who had started antiretroviral therapy with poor clinical and immunological status. Interventions to prevent mother to child transmission do not seem related to children treatment failure in this region. However, adherence to antiretroviral therapy in young children is good in this region. These results support the need for early antiretroviral treatment for HIV infected children at an earlier stage of the disease. This necessarily requires improved early infant diagnosis, through the involvement of fathers, the strengthening of the technical platform for screening and monitoring of children, and training of health staff. Also, cohort studies on prognostic factors for treatment failure in West African context are needed to investigate the issue of antiretroviral treatment response in these children.

Este estudo consiste em uma análise crítica sobre uma intervenção focada na melhoria da adesão de pessoas vivendo com aids ao tratamento antirretroviral, construída com base nas proposições da psicologia social construcionista, do referencial do Cuidado e do quadro da vulnerabilidade e dos direitos humanos. Essa intervenção foi testada pela primeira vez em um serviço de referência em DST/AIDS do estado de São Paulo, tendo sido conduzida por três profissionais de saúde previamente capacitadas, junto a pacientes em tratamento na instituição. Com o objetivo de descrever essa experiência e de compreender a viabilidade da condução da intervenção no contexto do SUS, por profissionais de diferentes especialidades, as três profissionais que integraram o estudo foram entrevistadas em profundidade, individualmente e em grupo. As entrevistas abordaram as reflexões das participantes sobre o processo de capacitação e a experiência prática na intervenção, incluindo seus relatos sobre os encontros que realizaram com os pacientes como parte da intervenção. Na discussão, enfocamos as principais facilidades e dificuldades encontradas pelas participantes ao longo do processo; as repercussões percebidas para sua atuação profissional e para o tratamento dos pacientes; e os desafios e sugestões levantados para uma futura implantação da intervenção em outros serviços. A proposta de intervenção mostrou-se factível do ponto de vista das profissionais que a conduziram e trouxe importantes reflexões para as práticas na área da assistência às pessoas vivendo com aids, contribuindo para o debate sobre as concepções teóricas e metodológicas que fundamentam as ações voltadas para a melhoria da adesão ao tratamento antirretroviral / This study presents a critical analysis of an intervention that sought to improve adherence of people living with aids to antiretroviral treatment based on the propositions of the social constructionist psychology, the Care reference and the vulnerability and human rights framework. This intervention was tested for the first time in an STD/AIDS reference service in the state of Sao Paulo. It was conducted by three previously trained health workers, along with patients undergoing treatment at the institution. Aiming to describe this experience and to understand the feasibility of the interventions conduction within SUS by workers from different areas, the three health workers who were part of the study were invited to answer to individual and group in-depth interviews. The interviews approached participants considerations regarding interventions training process and practical experience, including their reports about the meetings they held with patients as part of the intervention. In the discussion, we focused on the positive aspects and the main difficulties faced by participants throughout the process; the perceived results concerning their work practice and the patients treatment; and the challenges and suggestions proposed for a future implementation of the intervention in other services. The intervention was considered feasible from the health workers point of view and it brought important considerations about the practice developed to assist people living with aids, contributing to the debate concerning the theoretical and methodological conceptions that underlie the actions directed to improve the adherence to antiretroviral therapy

Thesis (MPhil (Industrial Psychology. Africa Centre for HIV/AIDS Management))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The advent of anti-retroviral therapy (ART) has bought hope and reprieve in a previously hopeless situation where there was no available drug to combat the virus with the result that AIDS deaths from chronic, untreated HIV infection became the major cause of morbidity and mortality especially in sub-Saharan Africa where the disease burden is highest. Since March 19, 1987, when the FDA approved Zidovudine for the treatment of AIDS, there has been great improvement in the prognosis and quality of life of HIV infected persons especially in sub- Saharan countries like Nigeria where the burden of HIV disease is high. Even though the treatment of HIV looked promising to all HIV sufferers, there were strict requirements for taking the ARVs, that meant patients had to be able to take the medication more than 95% of the prescribed time. The requirements also involved strict dietary restrictions that further made adherence to these medications very difficult indeed. In addition, the potential for side effects of the medications and its requirement for life-style modifications like abstinence from excess alcohol made sticking to the required regimen very cumbersome and rather patient unfriendly. Therefore, as the use of ARVs became more popular and effective, so did the problem of nonadherence continue to fester and deteriorate even further. Therefore, the problem of lack of optimum adherence to ARVs is one that potentially threatens all the gains of the discovery and use of potent, life-saving ARVs. Hence, there is now a need to look at how best to improve adherence to ARVs in the most innovative, cost-effective and patient-friendly manner. This study argues for the use of simple, locally-driven adherence strategies that overcome the low literacy and excessive alcoholism that are major factors preventing optimal adherence to ARVs amongst patients. / AFRIKAANSE OPSOMMING: Die intrede van anti-retrovirale behandeling het hoop en genade gebring aan ‘n voorheen hopelose situasie waar daar geen behandeling beskikbaar was om die virus te beveg nie, wat daartoe gelei het dat VIGS, as gevolg van MIV-infeksie wat nie behandel is nie, die grootste oorsaak van sterftes in veral Sub-Sahara Afrika is. Sedert 19 Maart 1987, wanneer Zidovudine goedgekeur is vir die behandeling van VIGS, is daar ‘n groot verbetering in die prognose en kwaliteit van lewe van MIV-geinfekteerde mense, veral in Sub-Sahara lande soos Nigerië waar die voorkoms van MIV hoog is. Hoewel de behandeling van MIV vir alle MIV-lyers belowend gelyk het, was daar streng vereistes vir die neem van anti-retrovirale behandeling. Daar was ook streng dieetkundige beperkinge wat die getrouheid tot die behandeling bemoeilik het. Die moontlike newe-effekte van die behandeling en nodige leefstyl veranderinge, soos byvoorbeeld weerhouding van oormatige alkohol gebruik, maak die behandeling redelik pasiënt onvriendelik. Soos die anti-retrovirale behandeling meer gewild en effektief geraak het, het die probleem van ongetrouheid ook toegeneem. Die probleem rondom ongetrouheid tot behandeling bedreig alles wat deur die behandeling gebied kan word. Daar is nou ‘n behoefte daaraan om getrouheid tot anti-retrovirale behandeling te bevorder in die mees innoverende, koste-effektiewe en pasiënt vriendelike manier. Die studie beveel eenvoudige, plaaslik gedrewe getrouheid-strategieë aan wat optimale getrouheid aan behandeling sal verseker.

Este estudo consiste em uma análise crítica sobre uma intervenção focada na melhoria da adesão de pessoas vivendo com aids ao tratamento antirretroviral, construída com base nas proposições da psicologia social construcionista, do referencial do Cuidado e do quadro da vulnerabilidade e dos direitos humanos. Essa intervenção foi testada pela primeira vez em um serviço de referência em DST/AIDS do estado de São Paulo, tendo sido conduzida por três profissionais de saúde previamente capacitadas, junto a pacientes em tratamento na instituição. Com o objetivo de descrever essa experiência e de compreender a viabilidade da condução da intervenção no contexto do SUS, por profissionais de diferentes especialidades, as três profissionais que integraram o estudo foram entrevistadas em profundidade, individualmente e em grupo. As entrevistas abordaram as reflexões das participantes sobre o processo de capacitação e a experiência prática na intervenção, incluindo seus relatos sobre os encontros que realizaram com os pacientes como parte da intervenção. Na discussão, enfocamos as principais facilidades e dificuldades encontradas pelas participantes ao longo do processo; as repercussões percebidas para sua atuação profissional e para o tratamento dos pacientes; e os desafios e sugestões levantados para uma futura implantação da intervenção em outros serviços. A proposta de intervenção mostrou-se factível do ponto de vista das profissionais que a conduziram e trouxe importantes reflexões para as práticas na área da assistência às pessoas vivendo com aids, contribuindo para o debate sobre as concepções teóricas e metodológicas que fundamentam as ações voltadas para a melhoria da adesão ao tratamento antirretroviral / This study presents a critical analysis of an intervention that sought to improve adherence of people living with aids to antiretroviral treatment based on the propositions of the social constructionist psychology, the Care reference and the vulnerability and human rights framework. This intervention was tested for the first time in an STD/AIDS reference service in the state of Sao Paulo. It was conducted by three previously trained health workers, along with patients undergoing treatment at the institution. Aiming to describe this experience and to understand the feasibility of the interventions conduction within SUS by workers from different areas, the three health workers who were part of the study were invited to answer to individual and group in-depth interviews. The interviews approached participants considerations regarding interventions training process and practical experience, including their reports about the meetings they held with patients as part of the intervention. In the discussion, we focused on the positive aspects and the main difficulties faced by participants throughout the process; the perceived results concerning their work practice and the patients treatment; and the challenges and suggestions proposed for a future implementation of the intervention in other services. The intervention was considered feasible from the health workers point of view and it brought important considerations about the practice developed to assist people living with aids, contributing to the debate concerning the theoretical and methodological conceptions that underlie the actions directed to improve the adherence to antiretroviral therapy

Introducción: El Sarcoma de Kaposi (SK) es una enfermedad neoplásica por Herpesvirus 8 en sinergia con el VIH. En la actualidad, no existe tratamiento con evidencia científica que respalde su efectividad y disminución de mortalidad. Objetivo: Evaluar si el uso del tratamiento oncológico disminuye la mortalidad a tres años de inicio de TARV de los pacientes con VIH y SK. Materiales y métodos: Un estudio transversal analítico se realizó en tres hospitales nacionales entre el 2008 y 2018. Los pacientes con SK se dividieron entre aquellos que recibieron TARV y aquellos que recibieron TARV con tratamiento oncológico. La historia clínica y la ficha TARV fueron revisadas. Resultados: La media poblacional fue de 45,02 años para los pacientes de bajo riesgo (DE:12,56). En el análisis bivariado se encontró asociación significativa entre mortalidad y abandono del TARV (p=0,046). No se identificó asociación significativa de la mortalidad al momento de elegir tratamiento oncológico más TARV o TARV solo como tratamiento inicial (PR: 0,92; IC 95% 0,326;2,575). En el modelo ajustado no se observa asociación significativa entre las variables Evento de Muerte y Tratamiento. Conclusiones: El tratamiento oncológico no disminuye la mortalidad a tres años de inicio de TARV de los pacientes con VIH y SK. Existe aumento de mortalidad en pacientes con VIH y SK que abandonan TARV. El Estadiaje de SK, Rango de CD4 Inicial, Orientación Sexual, entre otros, no resultaron influyentes en la mortalidad. Fallecieron 27,9 % de pacientes con VIH y SK durante el periodo de estudio. Existen diversos factores aumentan la incidencia de VIH y SK. / Introduction: Kaposi's Sarcoma (KS) is a neoplastic disease caused by Herpesvirus 8 in synergy with HIV. Currently, there is no treatment with scientific evidence to support its effectiveness and decrease in mortality. Objective: Assess whether the use of cancer treatment reduces mortality three years after starting ART in patients with HIV and KS. Materials and methods: An analytical cross-sectional study was conducted in three national hospitals between 2008 and 2018. KS patients were divided between those who received ART and those who received ART with cancer treatment. The clinical history and the ART file were reviewed. Results: The population mean was 45,02 years for low-risk patients (SD: 12,56). In the bivariate analysis, a significant association was found between mortality and abandonment of ART (p=0,046). No significant association was identified between mortality and initial treatment, be it cancer treatment plus ART or ART alone (PR: 0,92; 95% CI 0,326;2,575). In the adjusted model, no significant association was observed between the variables Death Event and Treatment. Conclusions: Cancer treatment does not reduce mortality three years after starting ART in patients with HIV and KS. There is an increase in mortality in patients with HIV and KS who abandon ART. KS Staging, Initial CD4 Range, Sexual Orientation, among others, were not influential in mortality. 27.9% of patients with HIV and KS died during the study period. There are several factors that increase the incidence of HIV and KS. / Tesis