title: Serious adverse events are uncommon with combination neonatal antiretroviral prophylaxis: a retrospective case review.
abstract: Six weeks of zidovudine (ZDV) is recommended for postnatal prophylaxis of HIV-exposed infants, but combination antiretrovirals are indicated if HIV transmission risk is increased. We investigated the frequency and severity of adverse events (AE) in infants receiving multiple drug prophylaxis compared to ZDV alone. In this retrospective review of 148 HIV-exposed uninfected infants born between 1997-2009, we determined clinical and laboratory AE that occurred between days of life 8-42. Thirty-six infants received combination prophylaxis; among those, a three-drug regimen containing ZDV, lamivudine, and nevirapine was most common (53%). Rates of laboratory AE grade ≥1 were as follows for the combination prophylaxis and ZDV alone groups, respectively: neutropenia 55% and 39%; anemia 50% and 39%; thrombocytopenia 0 and 3%; elevated aspartate aminotransferase 3% and 3%; elevated alanine aminotransferase 0 and 1%; hyperbilirubinemia 19% and 42%. Anemia occurred more frequently in infants who received three-drug prophylaxis compared to infants who received ZDV alone (63% vs. 39%, p = 0.04); all anemia AE were grade 1 or 2 in the three-drug prophylaxis group. Overall, 75% of infants on combination prophylaxis and 66% of infants on ZDV alone developed grade ≥1 AE (p = 0.32), and 17% of infants in either group developed grade ≥3 AE. Stavudine was substituted for ZDV in 23 infants due to anemia or neutropenia. After this antiretroviral change, 50% of evaluable infants demonstrated improvement in AE grade, and 25% had no change. In conclusion, low grade anemia, neutropenia, and hyperbilirubinemia occurred frequently regardless of the prophylactic regimen, but serious AE were uncommon. Although most AE were typical of ZDV toxicity, the combination of ZDV with lamivudine and nevirapine resulted in an increased frequency of low-grade anemia. Further studies are needed to identify prophylactic regimens with less toxicity for infants born to HIV-infected mothers.
authors.affiliation: Department of Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America.
authors.forename: Christiana
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, United States of America.
authors.forename: Jeri E
authors.initials: JE
authors.lastname: Forster
authors.affiliation: Department of Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Myron J
authors.initials: MJ
authors.lastname: Levin
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Department of Obstetrics and Gynecology, Denver Health Medical Center, Denver, Colorado, United States of America.
authors.forename: Jill
authors.initials: J
authors.lastname: Davies
authors.affiliation: Children's Hospital Colorado, Aurora, Colorado, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pappas
authors.affiliation: Children's Hospital Colorado, Aurora, Colorado, United States of America.
authors.forename: Kay
authors.initials: K
authors.lastname: Kinzie
authors.affiliation: Department of Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America.
authors.forename: Emily
authors.initials: E
authors.lastname: Barr
authors.affiliation: Department of Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: McFarland
authors.affiliation: Department of Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
mesh_terms: D000740:Anemia / Q000139:chemically induced; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine