Antenatal and neonatal antiretroviral therapy in HIV-infected women and their infants: a review of safety issues.
Specific interventions to prevent mother-to-child transmission (MTCT) include antiretroviral therapy, elective caesarean section and avoidance of breastfeeding. Rates of MTCT below 1-2% are now achievable in developed country settings. However, although the vast majority of infants born to HIV infected mothers are protected from acquisition of infection, most are exposed to antiretroviral drugs for which there is only limited information on toxicity. Increasing use of complex and potent combinations of antiretroviral drugs in pregnancy, particularly during the period of organogenesis, has raised many questions relating to pregnancy outcome and safety issues for the exposed children, both in the short and longer term. A shorter duration of pregnancy has been reported to be associated with taking protease inhibitors in pregnancy, particularly prolonged and early use, but this has been an inconsistent finding. Risk of congenital abnormalities may be increased with exposure to specific antiretroviral drugs, such as efavirenz, and certain combinations of Pneumonia Pneumocystis Carinii (PCP) prophylaxis and antiretroviral drugs, but there is no evidence of an excess of congenital malformations associated with exposure to zidovudine prophylaxis. Although data from observational studies and follow-up of children enrolled in clinical trials have not shown uninfected, zidovudine-exposed children to be at increased risk of adverse events including cancer in the short- to medium-term, the possibility that they may be at risk of cancer at older ages cannot be excluded. Concerns regarding mitochondrial dysfunction in children with foetal/neonatal exposure to zidovudine have arisen following a report from France of eight uninfected children with mitochondrial dysfunction, of whom two died. However, there is limited additional evidence of clinically evident mitochondrial disease in children exposed to antiretroviral therapy in utero or neonatally, and the absence of any excess mortality in large observational cohort studies of children born to HIV infected women and exposed to antiretroviral drugs is reassuring.
Thorne
Claire
C
Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College, 30 Guilford Street, WC1N 1EH London, UK. c.thorne@ich.ucl.ac.uk
Newell
Marie-Louise
ML
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D048588:Benzoxazines; D002986:Clinical Trials as Topic; D000013:Congenital Abnormalities / Q000209:etiology; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control* / Q000635:transmission; D017320:HIV Protease Inhibitors / Q000009:adverse effects; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D028361:Mitochondrial Diseases / Q000139:chemically induced; D010078:Oxazines / Q000009:adverse effects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000517:prevention & control; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D015215:Zidovudine / Q000009:adverse effects
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D015215:Zidovudine; C098320:efavirenz