Malnutrition, VIH et traitement antirétroviral dans les pays à ressources limitées

Introduction : Depuis les années 2000, la distribution du traitement antirétroviral hautement actif (TARVHA) dans les pays à bas et moyens revenus (PBMR) s’est accélérée. Dans ces milieux, l’épidémie du VIH s’est superposée à des conditions préexistantes de malnutrition. Le VIH et la malnutrition forment un cycle vicieux qui contribue à la détérioration des fonctions immunitaires et de l’état nutritionnel. Malgré l’accès au traitement, la malnutrition persiste comme déterminant de la progression de la maladie et de la mortalité chez les séropositifs. Par ailleurs, peu de données existent concernant les trajectoires et déterminants des statuts nutritionnels et immunologiques chez les patients débutant le TARVHA. Objectifs : Documenter les défis méthodologiques associés à la recherche nutritionnelle chez les personnes vivants avec le VIH (PVVIH) dans les PBMR. Investiguer les déterminants et trajectoires du statut nutritionnel à l’initiation et en cours du TARVHA. Investiguer l’association entre les fonctions immunologiques à l’initiation et au cours de la première année de TARVHA selon le statut nutritionnel. Méthodologie: Dans le cadre de la cohorte ATARAO (Mali), 250 PVVIH adultes naïfs au TARVHA ont été recrutés et suivis pendant 12 mois suite à l’initiation du traitement. Les données obtenues ont été jumelées à celles d’une étude prospective similaire provenant du Sénégal (n=372). Des analyses transversales et longitudinales ont été entreprises pour évaluer les covariables de la malnutrition à l’initiation et en cours de traitement. Parallèlement, la fiabilité des mesures anthropométriques collectées dans le cadre de la cohorte ATARAO a été documentée lors de deux sous-études. Finalement, une revue systématique de la littérature a été complétée pour investiguer la réponse immunologique selon le statut nutritionnel à l’initiation et en cours de traitement chez les PVVIH traités. Résultats: Seules les mesures de la taille et du poids se sont révélées fiables et ont pu être utilisées dans nos analyses prospectives. Le traitement a permis une amélioration initiale de l’état nutritionnel chez une majorité de patients. Par contre, ses effets ont atteint un plateau après 6 à 9 mois. Un an plus tard, la malnutrition persistait chez plusieurs patients vivants et actifs (entre 7 et 29 % selon la population et l’indicateur nutritionnel). Comme observé dans nos cohortes et revue systématique, l’attrition était fortement associée à la malnutrition. Par ailleurs, il n’existe pas de relation claire entre le statut immunologique et la malnutrition pré- ou post-HAART. La qualité et la quantité des évidences recensées ne nous permettent pas de tirer de conclusions définitives. Conclusions : Les évidences collectées suggèrent l’existence d’une association transversale et longitudinale entre les statuts nutritionnels et immunologiques chez les patients traités. Cependant, cette association ne fait pas consensus. L’état de la littérature ne nous permet pas de nous prononcer quant à l’impact de la malnutrition sur les fonctions immunologiques à l’initiation et eu cours de la première année de TARVHA. Les difficultés méthodologiques associées à la mesure de l’état nutritionnel ainsi que la forte attrition des patients malnutris suite à la mise sous traitement compliquent l’investigation de cette relation.Introduction: Over the past decade, access to highly active antiretroviral treatment (HAART) has rapidly increased in low and middle income countries (LMIC). In those settings, the HIV epidemic has been superimposed onto preexisting and prevalent conditions of malnutrition. HIV and malnutrition are part of a vicious cycle known to contribute to decreased nutritional status and immune function. Despite access to HAART, malnutrition, either at initiation or in the course of treatment, persists as a prognostic factor for poor health and mortality. Nonetheless, few data exist concerning nutritional trajectories or concerning the determinants of immune and nutritional status amongst patients initiating HAART. Objectives : To document the methodological challenges in nutritional research in LMIC. To investigate the determinants and trajectories of nutritional status at HAART initiation and in the first year of treatment. To investigate immune function and reconstitution according to baseline malnutrition. Results: Among anthropometric measures, only weight and height were found to be reliable. Consequently, these were the only anthropometric measures to be used in longitudinal analyses. Treatment led to a rapid amelioration of the nutritional status for a majority of patients. However, the initial effect quickly tapered off to reach a plateau 6 to 9 months post HAART. One year after treatment initiation malnutrition persisted in many patients active and alive (between 7-29% according to the population and nutritional indicator used). As observed in our cohorts and in our systematic review, attrition was strongly associated with baseline malnutrition. However, there does not appear to be a clear relation between the immunological response and nutritional status either at treatment initiation or during the course of HAART. The limited quantity and quality of available evidence did not permit us to draw definitive conclusions to that effect. Conclusions: In our cohort study, collected evidence suggested the existence of a cross-sectional and longitudinal association between nutritional and immunological statuses in treated patients. However, there exists no consensus concerning these associations. Based on uncovered data, we cannot draw conclusions on the impact of malnutrition on immune function and reconstitution either at baseline or within the first year post HAART. Methodological difficulties pertaining to nutritional status assessment iv and the frequent attrition of malnourished people initiating treatment, complicates the investigation of these relations; as is the coexistence of multiple inflammatory processes in those populations

Reliability of anthropometric measures in a longitudinal cohort of patients initiating ART in West Africa

<p>Abstract</p> <p>Background</p> <p>Anthropometric measurements are a non invasive, inexpensive, and suitable method for evaluating the nutritional status in population studies with relatively large sample sizes. However, anthropometric techniques are prone to errors that could arise, for example, from the inadequate training of personnel. Despite these concerns, anthropometrical measurement error is seldom assessed in cohort studies. We describe the reliability and challenges associated with measurement of longitudinal anthropometric data in a cohort of West African HIV+ adults .</p> <p>Methods</p> <p>In a cohort of patients initiating antiretroviral treatment in Mali, we evaluated nutritional status using anthropometric measurements(weight, height, mid-upper arm circumference, waist circumference and triceps skinfold). Observers with no prior experience in the field of anthropometry were trained to perform anthropometrical measurements. To assess the intra- and inter-observer variability of the measurements taken in the course of the study, two sub-studies were carried out: one at the beginning and one at the end of the prospective study. Twelve patients were measured twice on two consecutive days by the same observer on both study occasions. The technical error of measurement (TEM) (absolute and relative value), and the coefficient of reliability (R) were calculated and compared across reliability studies.</p> <p>Results</p> <p>According to the R and relative TEM, inter-observer reliabilities were only acceptable for height and weight. In terms of intra-observer precision, while the first and second anthropometrists demonstrated better reliability than the third, only height and weight measurements were reliable. Looking at total TEM, we observed that while measurements remained stable between studies for height and weight, circumferences and skinfolds lost precision from one occasion to the next.</p> <p>Conclusions</p> <p>Height and weight were the most reliable measurements under the study's conditions. Circumferences and skinfolds demonstrated less reliability and lost precision over time, probably as a result of insufficient supervision over the entire length of the study. Our results underline the importance of a careful observer's selection, good initial preparation, as well as the necessity of ongoing training and supervision over the entire course of a longitudinal nutritional study. Failure to do so could have major repercussions on data reliability and jeopardize its utilization.</p

Nutritional status of HIV-infected patients during the first year HAART in two West African cohorts

Objective: To examine the association between nutritional markers at initiation and during follow up in two different cohorts of HIV-infected adults initiating highly active antiretroviral therapy (HAART) in West Africa. Methods: The ATARAO study was a one year prospective study carried in Mali. It consisted of a sample of consecutive patients initiating HAART in one of four participating centers during that period. Data were collected at time of treatment initiation (baseline) and every 3 months thereafter. The ANRS 1290 study followed Senegalese patients recruited in similar conditions. Bivariate analyses were used to identify nutritional and immunological covariates of malnutrition at baseline. Longitudinal trajectories of body mass index, hemoglobin and albumin, and their associated factors, were evaluated using mixed linear models. Results: In ATARAO, 250 participants were retained for analyses; of which, 36% had a BMI &lt; 18.5 kg/m2, nearly 60% were anemic and 47.4% hypoalbuminemic at time of treatment initiation. At baseline, low hemoglobin, hypoalbuminemia and low CD4 levels were associated with a BMI &lt; 18.5 kg/m2. Similarly, low BMI, low albumin and low CD4 counts were linked to anemia; while, hypoalbuminemia was associated with low hemoglobin levels and CD4 counts. In ANRS, out of the 372 participants retained for analyses, 31% had a low BMI and almost 70% were anemic. At baseline, low BMI was associated with low hemoglobin levels and CD4 counts, while anemia was associated with low CD4 counts and female sex. While treatment contributed to early gains in BMI, hemoglobin and albumin in the first 6 months of treatment, initial improvements plateaued or subsided thereafter. Despite HAART, malnutrition persisted in both cohorts after one year, especially in those who were anemic, hypoalbuminemic or had a low BMI at baseline. Conclusion: In ATARAO and ANRS, malnutrition was common across all indicators (BMI, hemoglobin, albumin) and persisted despite treatment. Low BMI, anemia and hypoalbuminemia were associated with attrition, and with a deficient nutritional and immunological status at baseline, as well as during treatment. In spite of therapy, malnutrition is associated with negative clinical and treatment outcomes which suggests that HAART may not be sufficient to address co-existing nutritional deficiencies

Characterization of immunization approaches to promote axon regeneration

Myelin-associated axon growth inhibitors such as Nogo and myelin-associated glycoprotein (MAG) play an important role in the failure of axon regeneration in the adult mammalian central nervous system (CNS). One strategy to neutralize these inhibitors is a vaccination approach using immunization with myelin in incomplete Freund's adjuvant (IFA). In the present study, I compared the effectiveness of (i) immunizing with recombinant MAG/Nogo versus myelin, (ii) different adjuvants (IFA vs Alum) and (iii) different immunization frequencies for their capacity to promote spinal cord regeneration in adult SJL/J mice. The length of axon regeneration was similar in all the groups studied. However the robustness of the regenerative response, i.e., the number of axons that grew and the percentage of mice showing regeneration was greater in myelin treated groups. Alum also led to a greater degree of sprouting compared with. IFA. Finally, the two immunization frequencies tested were found to differentially affect the sprouting response. Compared to previous work on BALB/c mice, fewer regenerating fibers were seen in immunized SJL/J mice. This may be due to the greater depth of lesion in the present study as compared to earlier work or to possible differences in the mouse strains used. This work shows that immunizations with Alum as the adjuvant is as effective or better than IFA, and that immunization with the two known inhibitors (MAG/Nogo) is effective at promoting axon regeneration although not as much as with whole myelin