title: Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated.
abstract: OBJECTIVE
  Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed.
  
  
  METHODS
  Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1.
  
  
  METHODS
  Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole + nevirapine and the cotrimoxazole + placebo groups were compared using negative-binomial regression.
  
  
  RESULTS
  Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole + nevirapine and cotrimoxazole + placebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole + nevirapine versus cotrimoxazole + placebo.
  
  
  CONCLUSIONS
  Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.
authors: Makerere University, Johns Hopkins University Research Collaboration, Kampala, Uganda.
authors: Jim
authors: J
authors: Aizire
authors: Mary Glenn
authors: MG
authors: Fowler
authors: Jing
authors: J
authors: Wang
authors: Avinash K
authors: AK
authors: Shetty
authors: Lynda
authors: L
authors: Stranix-Chibanda
authors: Moreen
authors: M
authors: Kamateeka
authors: Elizabeth R
authors: ER
authors: Brown
authors: Steve G
authors: SG
authors: Bolton
authors: Philippa M
authors: PM
authors: Musoke
authors: Hoosen
authors: H
authors: Coovadia
mesh_terms: D000328:Adult; D000740:Anemia / Q000139:chemically induced*; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015153:Blotting, Western; D001942:Breast Feeding / Q000009:adverse effects; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D005076:Exanthema / Q000139:chemically induced*; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D008895:Milk, Human / Q000821:virology; D009503:Neutropenia / Q000139:chemically induced*; D019829:Nevirapine / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects; D014454:Uganda / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D019829:Nevirapine