Maternal vitamin A status and mother-to-child transmission of HIV in West Africa

Field: Medicine (Health Sciences)

Observational studies in Malawi [1] and the United States [2] have shown an association between low plasma vitamin A status during pregnancy and an increased risk of mother-to-child transmission (MTCT) of HIV. However, this observation was not confirmed in more recent American studies [3,4]. Trials evaluating the efficacy of retinol and carotene supplementation in reducing MTCT have been initiated in Africa. According to the currently available results, vitamin A supplementation does not seem to have any significant effect in reducing MTCT [5,6]. A biased estimation of the effect of vitamin A supplementation, if any, should not be ruled out in those studies. Also, vitamin A deficit in HIV-infected women is multifactorial: intake reduction; impaired release of retinol binding protein (RBP); and excess urinary loss of retinol [7]. These factors could act differently according to the background of endemic vitamin A deficit and the stage of HIV disease. Observations in different settings could therefore be useful to obtain a better understanding of the relationship between vitamin A and MTCT of HIV. This study was performed within the DITRAME ANRS 049a trial, which was placebo-controlled and evaluated the efficacy of a short regimen of zidovudine (ZDV) in reducing MTCT in breastfed children in Abidjan (Côte d'Ivoire) and Bobo-Dioulasso (Burkina Faso) [8]. At inclusion in the trial, i.e. at 36–38 weeks of gestation, a sample of maternal blood was collected protected from light and serum samples were frozen at −80°C at the CeDReS (Abidjan) and Centre Muraz (Bobo-Dioulasso) laboratories until testing. Samples were shipped for analysis at the Centre Hospitalier Universitaire of Bordeaux (France); retinol by high phase liquid chromatography and RBP by nephelometry. Vitamin A status was evaluated by the retinol level and the retinol : RBP equimolar ratio. Moderate deficit was defined by retinol of less than 30 μg/dl or retinol : RBP of less than 1.3, and severe deficit by retinol of less than 20 μg/dl or retinol : RBP of less than 0.8. Paediatric HIV infection was defined by a positive polymerase chain reaction test at day 180 after birth or earlier. In the present analysis, we considered the cases of paediatric infection up to 90 days after birth. Maternal HIV viral load was assessed by a RNA technique (Bayer-Chiron, Quantiplex 340TM, Version 3.0, E. Walpole, MA, USA) with a threshold level of 50 copies/ml. Comparisons of mean maternal vitamin A level and deficit proportions between infected and uninfected children used Student's t test and the chi-squared test, respectively. The collection of samples for vitamin A analysis was initiated in May 1996 in Bobo-Dioulasso and March 1997 in Abidjan. Among the 280 maternal samples expected up to the end of the trial (February 1998), 241 could be analysed for vitamin A status (86%), the rest being inadequately collected or not properly stored. The HIV infection status was known in 234 children, equally distributed between ZDV (118) and placebo (116). At 3 months of life, 54 children (23%) were infected. Levels of retinol, RBP and retinol : RBP were comparable between transmitting and non-transmitting mothers (Table 1). Similarly, the proportions of women with moderate and severe vitamin A deficits were comparable according to the HIV infection status of their children (Table 1). Among the maternal or birth factors studied, only maternal CD4 lymphocytes and viral load at inclusion were significantly and independently associated with MTCT: odds ratios were 1.28 (95% confidence interval 1.02–1.61) for a decrease of 100 CD4 lymphocytes/mm3 and 5.7 (1.8–17.7) for maternal viral load above the median (20 000 copies/ml). These results were not modified when adjusting for the site (Abidjan and Bobo-Dioulasso) and the treatment (ZDV and placebo).Table 1: Maternal vitamin A status during pregnancy (36–38 weeks of gestation) and paediatric HIV infection at 3 months of life in the DITRAME ANRS 049a trial in Abidjan (Côte d'Ivoire) and Bobo-Dioulasso (Burkina Faso). The observed frequencies of moderate and severe vitamin A deficit based on the serum retinol level in HIV-positive pregnant women were compatible with those of other African studies, one-third of HIV-positive women presenting with moderate deficit [1,6]. However, a statistical relationship between the retinol level and MTCT risk was not found. In the most recently published randomized trial [6], vitamin A supplementation reduced prematurity overall but MTCT was reduced among premature infants only. In the Tanzanian trial [9], vitamin A supplementation alone did not show any benefit for maternal and neonatal indicators, whereas it was the case for supplementation with multiple vitamins. In our study, statistical power could not explain the absence of statistical association between vitamin A deficiency and MTCT because the sample size allowed us a power of 95% to detect a difference of moderate retinol deficit such as 30% among non-transmitting mothers and 60% among transmitters, as in the Malawi cohort [1]. We chose to measure RBP in order to determine whether its depletion could explain retinol deficits and be a marker of advanced HIV disease. No association was found between RBP and the risk of MTCT. Furthermore, the retinol : RBP ratio, which reflects low dietary intakes of retinol and carotene, was also not associated with MTCT. These in-depth biological observations could partly explain the poor benefits obtained in retinol and carotene supplementation trials [6,9]. The mechanisms by which retinol deficit could be modulated in HIV-positive women and therefore supplementation could be efficacious for the reduction of MTCT seem to be complex. Supplementation by itself may thus not provide systematic benefits, especially because the association of maternal vitamin A status and MTCT risk is not universally observed. Acknowledgements The authors are grateful to Jean-Paul Levy and Chantal Canon (ANRS), Michel Clerc, Liliane Dubourg (CHU de Bordeaux), and to the staff of the DITRAME Study Group in Abidjan and Bobo Dioulasso, for support and contributions to this study. Katia Castetbonab Olivier Manigartc Dominique Bonardd Marie-Josée Thomase Marie-France Dumone Denis Malvyaf Philippe Van de Perrec François Dabisa for the DITRAME Study Group*