Mother’s CD4+ Count Moderates the Risk Associated with Higher Parity for Late Postnatal HIV-Free Survival of Breastfed Children: An Individual Patient Data Meta-Analysis of Randomized Controlled Trials

Abstract

Risk association studies of late postnatal outcomes for children breastfed by HIV-1 positive mothers have had inconsistent findings and have not explored interactions among risk factors. This study addresses these limitations through an individual patient data (IPD) metaanalysis of HIV-free survival outcomes of nine randomized controlled trials to prevent early mother-to-child transmission of HIV-1. The pooled sample consisted of 3,324 African children in resource-limited settings who survived to age 28 days and were at-risk of acquiring HIV through breast milk. Based on a proportional hazards mixed effects meta-analysis, the composite endpoint of HIV-1 infection and all-cause mortality was found to be significantly associated with maternal immune status (CD4 ? C350 cells/ mm 3 , HR 0.59 95% CI (0.39, 0.87)), infant preterm delivery (gestational age \37 weeks, 1.40 (1.03, 1.89)), infant oral candidiasis infection (1.87, (1.53, 2.29)), and occurrence of breast abnormality before breastfeeding cessation (2.56 (1.90, 3.46)). A significant interaction between mother's parity (any previous pregnancy) and CD4 ? count C350 (HR 0.63 (0.40, 0.99), P-value = 0.045) suggested that higher CD4 ? count offsets the risk associated with higher parity. Further research is needed to elucidate the moderating effect of immune status on the risk associated with high parity and adverse late postnatal outcomes for infants breastfed by HIV-infected mothers in the absence of antiretroviral treatment.Keywords Gravidity Á Human Immunodeficiency Virus Á Meta-analysis Á Parity Á Prevention of maternal to child transmission of HIV Á Risk factorsResumen Estudios sobre los factores de riesgo para los hijos de madres infectadas con VIH-1 han sido inconsistentes y los investigadores no han estudiado las interacciones entre esos factores. En una respuesta a estas limitaciones, este estudio presenta un meta-análisis, basado en los datos de participantes individuales, de la supervivencia sin transmisión de VIH para niños que tienen un riesgo de adquirir el virus durante el periodo del amamantamiento. En total, la muestra incluyó 3,324 niños de naciones africanas que vivieron en circunstancias de recursos limitados, sobrevivieron a la edad de veintiocho días y que estuvieron en riesgo de adquirir VIH por la lactancia materna. Con un avanzado modelo de Cox, que tuvo effectos mezclados, se descubrió que la transmisión VIH y la mortalidad se asoció con el recuento de células CD4 ? (CD4 ? C350 células/ll, cociente de riesgo instantáneo (HR) 0.59 95% intervalo de confianza (0.39, 0.87)), el parto prematuro (la edad de gestación \37 semanas, 1.40 (1.03, 1.89)), una infección infantil de candidiasis oral (1.87, (1.53, 2.29)), y el acontecimiento de una enfermedad de los senos antes de que el periodo de lactancia se hubiera terminado (2.56 (1.90, 3.46)). Una interacción importante entre el número de partos y el recuento de células CD4 ? (HR 0.63 (0.40, 0.99), P = 0.045) sugiere que un alto recuento de células CD4 ? descuenta el riesgo asociado con el alto nú...

The Cost-Effectiveness of Different Feeding Patterns Combined with Prompt Treatments for Preventing Mother-to-Child HIV Transmission in South Africa: Estimates from Simulation Modeling

“…A reference showed a significant correlation between associated mothers'CD4 counts and infants' HIV status. they found that if the concentration of CD4 counts≥350 cells/mm 3 , the HR of infants infected HIV was 0.59 [80]. Delicio found that if the CD4 cell counts lower than 350 cells/mm 3 , it would increase the risk of MTCT more than 12 times.…”