title: Antiretroviral Treatment in HIV-1-Positive Mothers: Neurological Implications in Virus-Free Children.
abstract: Since the worldwide introduction of antiretroviral therapy (ART) in human immunodeficiency virus type 1, HIV-1-positive mothers, together with HIV-1 testing prior to pregnancy, caesarian birth and breastfeeding cessation with replacement feeding, a reduction of HIV-1 mother-to-child transmission (MTCT) has been observed in the last few years. As such, an increasing number of children are being exposed in utero to ART. Several questions have arisen concerning the neurological effects of ART exposure in utero, considering the potential effect of antiretroviral drugs on the central nervous system, a structure which is in continuous development in the fetus and characterized by great plasticity. This review aims at discussing the possible neurological impairment of children exposed to ART in utero, focusing attention on the drugs commonly used for HIV-1 MTCT prevention, clinical reports of ART neurotoxicity in children born to HIV-1-positive mothers, and neurologic effects of protease inhibitors (PIs), especially ritonavir-"boosted" lopinavir (LPV/r) in cell and animal central nervous system models evaluating the potential neurotoxic effect of ART. Finally, we present the findings of a meta-analysis to assess the effects on the neurodevelopment of children exposed to ART in utero.
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Avenida da Engenharia, Cidade Universitária, 50740-600 Recife, Brazil. avccbio@gmail.com.
authors.forename: Antonio Victor Campos
authors.initials: AV
authors.lastname: Coelho
authors.affiliation: Institute for Maternal and Child Health, Scientific Institute for Research, Hospitalization and Care (IRCCS) Burlo Garofolo, 34137 Trieste, Italy. tricaricopa@gmail.com.
authors.forename: Paola Maura
authors.initials: PM
authors.lastname: Tricarico
authors.affiliation: Institute for Maternal and Child Health, Scientific Institute for Research, Hospitalization and Care (IRCCS) Burlo Garofolo, 34137 Trieste, Italy. fulvio.celsi@gmail.com.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Celsi
authors.affiliation: Institute for Maternal and Child Health, Scientific Institute for Research, Hospitalization and Care (IRCCS) Burlo Garofolo, 34137 Trieste, Italy. crovella@burlo.trieste.it.|Department of Developmental and Reproductive Sciences, Genetic Unit, University of Trieste, 34127 Trieste, Italy. crovella@burlo.trieste.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D019468:Disease Management; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000635:transmission / Q000821:virology*; D015497:HIV-1; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D018811:Maternal Exposure; D015201:Meta-Analysis as Topic; D009035:Mothers; D065886:Neurodevelopmental Disorders / Q000209:etiology / Q000517:prevention & control; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D019380:Anti-HIV Agents
keywords: antiretroviral therapy; autophagy; epigenetic mechanisms; neuro-inflammation; neurological impairment