Etude De Determinants De La Transmission Du Vih De La Mere a L’Enfant Au Burkina Faso

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Etude De Determinants De La Transmission Du Vih De La Mere a L’Enfant Au Burkina Faso UNIVERSITE LIBRE DE BRUXELLES ANNEE 2003-2004 THESE Pour obtenir le grade académique de DOCTEUR EN SCIENCES AGRONOMIQUES ET INGENIERIE BIOLOGIQUE FACULTE DES SCIENCES Par Mr Olivier MANIGART ETUDE DE DETERMINANTS DE LA TRANSMISSION DU VIH DE LA MERE A L’ENFANT AU BURKINA FASO Jury : Directeur de thèse : Mr le Professeur Philippe VAN DE PERRE, co- Directrice de thèse : Mme le Professeur Carine VAN LINT, Président : Mr le Professeur Georges HUEZ, Mme le Professeur Véronique HALLOIN, Mr le Professeur Nicolas MEDA, Mr le Professeur John WERENNE, Mr le Professeur Arsène BURNY, Mr le Professeur Philippe LEPAGE. 1 Couverture : route Ouagadougou – Bobo-Dioulasso, juillet 2003. 2 A ma petite fille adorée, Isia, 3 4 Je me suis réveillé, tiré de la lourde torpeur d’une sieste de saison sèche par des cris stridents et des acclamations saccadées qui provenaient du devant de ma cour. Je me suis levé lourdement et j’ai écarté le pagne qui protège de la lumière et de la chaleur tellement vives en cette période, pour découvrir que les « Masques » étaient descendus dans la rue. Au contraire, la lumière était diffuse et sinistre et la lourdeur de l’air était telle qu’une angoisse profonde m’étreignit instantanément. En général, les « Masques » sortent lors de périodes rituelles – ce qui n’était pas le cas – ou, au cours de phénomènes étranges. Ce sont les initiés qui portent le masque et qui fustigent à tout-vas : c’est souvent l’occasion de corrections exemplaires pour ceux qui se sont mal comportés… ou de vengeances personnelles. J’ai levé les yeux pour observer le ciel : il était obscurci d’un halo de nuages circulaire d’un diamètre de ce qui semblait être plusieurs kilomètres. Le contour était cintré d’un arc-en-ciel et c’est cela qui donnait cette lumière claire-obscure. Jamais je n’avais observé un tel phénomène ; pour peu, j’en aurais suivi les Masques. Les gens d’ici disent que lorsque cela se produit, une personne importante va mourir. Moi, j’ai plutôt pensé à la détresse des milliers de personnes qui souffrent dans ce pays déjà si pauvre. Ma réalité ; ma détresse ! Anonyme (festival Sida Ka Taa, 2001) 5 6 TABLES DES MATIERES : Résumé : .................................................................................................................................. 23 Abstract : .................................................................................................................................. 25 Liste des tableaux :................................................................................................................... 27 Liste des figures : ..................................................................................................................... 29 Abréviations : ........................................................................................................................... 31 Définitions :.............................................................................................................................. 35 Données démographiques et sanitaires du Burkina Faso :....................................................... 37 I. INTRODUCTION : .............................................................................................................. 39 1. Présentation du sujet : .......................................................................................................... 41 2. Origine et évolution génétique du virus :............................................................................. 41 2.1. Origines des virus VIH-1 et VIH-2 :................................................................................. 41 2.2. Causes et conséquences de la variabilité........................................................................... 43 2.2.1. Faible fidélité de la transcriptase inverse :............................................................. 45 2.2.2. Fort taux de réplication .......................................................................................... 45 2.2.3. Recombinaisons ..................................................................................................... 45 2.2.4. Pressions de sélection du système immunitaire : ................................................... 47 2.2.5. Conséquences :....................................................................................................... 47 3. Classification du VIH-1 : ..................................................................................................... 49 3.1. Trois groupes, 9 sous-types et plusieurs formes recombinantes (CRF) :.......................... 49 3.2. Critères de définition des sous-types et CRF : .................................................................. 49 4. Variabilité du VIH et conséquences :................................................................................... 49 4.1. Efficacité des tests de sérodiagnostic et de suivi des patients :......................................... 51 4.2. Mise au point d’un vaccin :............................................................................................... 51 4.3. Réponse aux antirétroviraux : ........................................................................................... 53 5. Le HMA : un outil pour l’étude de la variabilité du VIH ?.................................................. 55 5.1. Outils dont on dispose pour étudier la variabilité : ........................................................... 55 5.1.1. Le séquençage suivi d’analyses phylogénétiques : ................................................ 55 5.1.2. Le sérotypage : ....................................................................................................... 55 5.1.3. Les techniques de PCR spécifiques :...................................................................... 55 5.1.4. La technique d’Heteroduplex Mobility Assay: ...................................................... 55 6. La problématique des surinfections : ................................................................................... 57 7 6.1. La surinfection chez l’adulte :........................................................................................... 57 6.2. La surinfection dans le contexte de la TME :.................................................................... 61 7. Modalité de la TME et impact de la variabilité virale : ....................................................... 63 7.1. Transmission in utero :...................................................................................................... 65 7.1.1. Modulation des mécanismes immunitaires maternels durant la grossesse : .......... 65 7.1.2. Timing de la transmission in utero :....................................................................... 67 7.1.2. Histologie du placenta :.......................................................................................... 67 7.1.3. Mécanismes potentiels de la transmission in utero :.............................................. 69 7.1.4. Transmission de souches SI versus NSI :............................................................... 71 7.1.5. Passage de variants mineurs ? ................................................................................ 71 7.1.6. Génotype et transmission in utero :........................................................................ 73 7.2. Transmission intra-partum :.............................................................................................. 73 7.2.1. Timing de la transmission intra-partum : ............................................................... 73 7.2.2. Immunologie du tractus génital féminin associée au VIH :................................... 75 7.2.3. Insertions et délétions ?......................................................................................... 75 7.3. Transmission post-partum :............................................................................................... 77 7.3.1. Histologie de la glande mammaire :....................................................................... 77 7.3.2. Variabilité virale et transmission par l’allaitement : .............................................. 79 7.3. 3. Virus libres ou formes provirales :........................................................................ 79 7.3.4. Immunologie du compartiment mammaire associée au VIH et à la TME :........... 81 7.4. Portes d’entrée chez le nouveau-né :................................................................................. 83 8. Impact de la charge virale sur la TME dans le contexte d’un traitement court à l’AZT (Zidovudine) :........................................................................................................................... 87 8.1. Dynamique de la réplication virale lors d’une monothérapie : ......................................... 87 8.2. Impact de la charge virale dans le sang sur la TME : ....................................................... 89 8.3. Impact de la charge virale dans les sécrétions cervico-vaginales (SCV) sur la TME :.... 89 8.3.1. Modulations physiologiques du tractus génital associées à une susceptibilité infectieuse : ............................................................................................................ 91 8.3.2. Corrélation de la CV plasmatique avec la CV des sécrétions cervicovaginales :.. 91 8.3.3. Facteurs associés à la présence du VIH dans les SCV :........................................ 91 8.4. Impact de la charge virale dans le lait maternel sur la TME :........................................... 93 8.4.1.
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