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Étude du réservoir cellulaire du VIH-1 en fonction du traitement chez l’enfant infecté par transmission verticaleCanape, Jade 08 1900 (has links)
Contexte :
Notre incapacité à guérir le VIH/SIDA vient au moins en partie du fait que le VIH établit et maintient des réservoirs cellulaires à l'abri des effets de la thérapie antirétrovirale combinée (cART) et de l'immunité de l'hôte. Alors que les composantes des réservoirs sont bien connues chez les adultes, la composition et l'évolution de ces réservoirs chez les enfants infectés verticalement sont moins bien comprises. Notre objectif était d'examiner les effets de l’âge de l’enfant au moment de l’initiation de la cART et de l'obtention d'une suppression virale soutenue (SVS) sur la taille et la nature du réservoir du VIH chez les enfants et les adolescents.
Méthodes : À l'aide de la méthode HIV-Flow, la taille et la distribution des sous-types cellulaires du réservoir viral compétent pour la traduction ont été évaluées dans les cellules T CD4+ purifiées obtenues d'enfants et d'adolescents infectés verticalement (n=34) qui participaient à l'étude EPIC4 et qui ont été groupés selon l'âge (0-5, 5-10, 10-18 ans) et l’atteinte de la SVS.
Résultats : Les différences de taille de réservoir entre les participants masculins et féminins ou entre les groupes d'âge n'étaient pas statistiquement significatives (p=0.5003, p=0.9410). Les cellules T CD4+ naïves étaient les principales contributrices au réservoir de cellules productrices de p24 dans tous les groupes d'âge, comparé aux cellules à mémoire centrale (CM), à mémoire effectrice (EM) et terminalement différenciées (TD) (p=0.001, p<0.0001, p<0.0001). La forte représentation des cellules T CD4+ naïves dans le pool total de cellules T CD4+ (⁓68% à >80%) peut expliquer cette contribution. Les cellules CM avaient tendance à présenter des fréquences plus élevées de cellules p24+ chez les adolescents par rapport aux groupes d'âge plus jeunes. Une corrélation négative a été observée entre la fréquence des cellules p24+ et la proportion de vie sous SVS (r=-0.3215, p=0.0318) ainsi que la proportion de vie sous cART efficace (r=-0.3197, p=0.0327).
Conclusion : Contrairement aux adultes infectés par le VIH, le réservoir cellulaire hébergeant le VIH compétent pour la traduction chez les enfants et les adolescents infectés verticalement est principalement composé de cellules T CD4+ naïves, avec un profil de distribution se rapprochant progressivement avec l’âge de celui des adultes. Ces résultats éclairent et renforcent les orientations fondées sur des données probantes pour la prise en charge clinique et le traitement de l'infection verticale par le VIH. / Background: Our inability to cure HIV/AIDS stems at least in part from the fact that HIV establishes
and maintains cellular reservoirs where it shelters from the effects of combination antiretroviral
therapy (cART) and host immunity. Whereas reservoir components are well known in adults, the
composition and evolution of these reservoirs in vertically infected children are incompletely
understood. Our objective was to examine the effects of the timing of cART initiation and
achievement of sustained viral suppression (SVS) on the size and nature of the HIV reservoir in
children and adolescents. Methods: Using the HIV-Flow method, size and cell subset distribution
of the translation competent viral reservoir were assessed in purified CD4+ T cells from vertically
infected children and adolescents (n=34) with and without SVS, who were enrolled in the EPIC4
study and stratified according to age (0-5, 5-10, 10-18 years) and achievement/duration of SVS.
Results: Differences in reservoir size between male and female participants or across age groups
were not statistically significant (p=0.5003, p=0.9410). Naïve CD4+ T cells were the main
contributor to the pool of p24-producing cells in all age groups as compared to central memory
(CM), effector memory (EM), and terminally differentiated (TD) (p=0.001, p<0.0001, p<0.0001).
The large representation of naïve CD4+ T cells in the total CD4+ T cells pool (⁓68% to >80%) can
explain this contribution. CM cells tended to carry higher frequencies of p24+ cells in adolescents
compared to younger age groups. A negative correlation was observed between the frequency of
p24-positive cells and the proportion of life under SVS (r=-0.3215, p=0.0318) as well as the
proportion of life under effective cART (r=-0.3197, p=0.0327). Conclusion: Unlike HIV-infected
adults, the cellular reservoir harboring translation competent HIV in vertically infected children
and adolescents is mostly comprised of naïve CD4+ T cells, with a distribution profile progressively
transitioning to that of adults. These results inform and reinforce evidence-based guidance for
the management of vertical HIV infection.
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Factors that influence adherence to antiretroviral therapy among adults at Nekemte Referral Hospital in EthiopiaAmsalu Belew Zeleke 09 April 2013 (has links)
The objectives of the study were (1) to quantify adherence rate among the study participants in the ART unit and (2) to identify factors that contribute to non-adherence. This cross sectional study was carried out at Nekemete referral clinic. Data was collected using a self-developed structured questionnaire where a total of 338 participants grouped into adherent and non-adherent based on a score derived from an adherence assessment were interviewed. Data was analysed using the Statistical Package for Social Sciences (SPSS) version 17.0. By using multivariate analysis of variables identified as correlates of adherence, non-adherence was common among those; with age between 18-30 yrs, with no education, who were not married, who had no pipe water supply, those with no electricity in the house, who perceived had no access to assistance from providers, who perceived the health care providers (HCPs) did not keep information confidentially, who had a language barrier with providers, and who were treated with a psychiatric illness. The study concludes that adherence is multi-factorial and varies significantly by individual and care setting. Psychosocial factors were found to impact adherence and should be analysed in more detail by further studies. Three psychosocial factors were independently associated with poor adherence: the study found that patients perceiving poor access; those perceiving problems in information confidentiality (and possibly experiencing stigmatisation); and having psychiatric morbidity (and possibly with less social support) are more likely to be non-adherent. Furthermore, individuals without electricity and those without piped water supply, implying low income, are at risk for non-adherence / Health Studies / M.A. (Public Health)
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Factors that influence adherence to antiretroviral therapy among adults at Nekemte Referral Hospital in EthiopiaAmsalu Belew Zeleke 09 April 2013 (has links)
The objectives of the study were (1) to quantify adherence rate among the study participants in the ART unit and (2) to identify factors that contribute to non-adherence. This cross sectional study was carried out at Nekemete referral clinic. Data was collected using a self-developed structured questionnaire where a total of 338 participants grouped into adherent and non-adherent based on a score derived from an adherence assessment were interviewed. Data was analysed using the Statistical Package for Social Sciences (SPSS) version 17.0. By using multivariate analysis of variables identified as correlates of adherence, non-adherence was common among those; with age between 18-30 yrs, with no education, who were not married, who had no pipe water supply, those with no electricity in the house, who perceived had no access to assistance from providers, who perceived the health care providers (HCPs) did not keep information confidentially, who had a language barrier with providers, and who were treated with a psychiatric illness. The study concludes that adherence is multi-factorial and varies significantly by individual and care setting. Psychosocial factors were found to impact adherence and should be analysed in more detail by further studies. Three psychosocial factors were independently associated with poor adherence: the study found that patients perceiving poor access; those perceiving problems in information confidentiality (and possibly experiencing stigmatisation); and having psychiatric morbidity (and possibly with less social support) are more likely to be non-adherent. Furthermore, individuals without electricity and those without piped water supply, implying low income, are at risk for non-adherence / Health Studies / M.A. (Public Health)
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