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Traitement antirétroviral précoce des nourrissons infectés par le VIH-1 : évaluation de la réponse virologique à court et moyen termes dans un pays d’Afrique sub-saharienne (Cameroun)

Abstract : Introduction: Since 2015, the WHO recommends to start antiretroviral treatment promptly in all HIV-infected children in order to reduce HIV related mortality. Despite increasing availability of screening tests and antiretroviral drugs, early initiation of antiretroviral treatment (ART) remains challenging in resource-limited countries. The ANRS 12140-Pediacam study assesses feasibility, effectiveness and tolerability in routine practice of early treatment of HIV-infected children in Cameroon. Objectives: The objectives of this thesis are to study mortality and virologic response at 2 and 4 years of early initiation of ART in HIV-infected infants and identify factors associated with virologic success. Methods: The analysis concerned the 190 HIV-infected infants who have initiated ART no later than 1 year (median=4 months) and were enrolled in the 3 Cameroon clinical sites involved in the PEDIACAM prospective cohort study since 2007. The first study evaluated adherence criterium based on the number of missed doses as reported through an adherence questionnaire in oerder to detect virologic failure in infants. The second study concerned the evaluation of the frequency and the factors associated with virologic success and mortality at 2 years of ART initiation, using competing risk regression. The third study concerned the evolution of virologic response between 2 and 4 years of QRT initiation depending on virologic status achieved at 2 years of ART initiation. Results: The performances of adherence questionnaire administered to the infant's caregiver are limited; the positive predictive value is low for detecting virologic failure in the absence of viral load exam. The mortality is high at 1 year after early ART initiation (18.0% [95% CI: 13.0 – 24.0]). The mortality is 3.3% [95%CI: 0.4 – 6.2] between 2 and 4 years of ART initiation. The probability of achieving at least once virologic success within the first 2 years of ART is around 80.0% but the probability of maintaining virologic success for at least 6 months was 67% for threshold=1000 copies/mL and 60% for threshold=400 copies/mL. At 4 years of ART initiation, the proportion of virologic success (viral load<400 copies/mL) is 75.2% [68.3-82.1]) in the 144 children still alive among whom viral load exam was not performed. The only factor associated with virologic success at 2 years of ART initiation is good adherence as reported by the caregiver. Et seuls un succès virologique obtenu à 2 ans et l’initiation plus récente du traitement antirétroviral sont associés à un charge virale contrôlée à 4 ans.Conclusion: Although the interest of early ART in HIV-infected infants is demonstrated, the mid and long term virologic success pass through strategies enhancing supporting steady and daily administration of drugs and regular monitoring of virologic response. The steady evaluation of adherence as reported by questionnaire has a very low performance for early detecting virologic failure. It is urgent to widely get access to routine viral load exam in resource-limited countries for quickly detecting virologic failures in children receiving antiretroviral treatment.
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Francis Ateba Ndongo. Traitement antirétroviral précoce des nourrissons infectés par le VIH-1 : évaluation de la réponse virologique à court et moyen termes dans un pays d’Afrique sub-saharienne (Cameroun). Santé publique et épidémiologie. Université Paris Saclay (COmUE), 2017. Français. ⟨NNT : 2017SACLS322⟩. ⟨tel-02426005⟩

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