Extended Prophylaxis With Nevirapine and Cotrimoxazole Among HIV-exposed Uninfected Infants Is Well Tolerated

AIDS. 2012 Jan 28;26(3):325-33. doi: 10.1097/QAD.0b013e32834e892c.

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.

Design: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00074412.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia / chemically induced*
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Blotting, Western
  • Breast Feeding / adverse effects
  • Drug Administration Schedule
  • Drug Eruptions / etiology
  • Exanthema / chemically induced*
  • Female
  • HIV Seropositivity / drug therapy*
  • HIV Seropositivity / epidemiology
  • HIV Seropositivity / transmission
  • HIV-1 / drug effects*
  • Humans
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Male
  • Milk, Human / virology
  • Neutropenia / chemically induced*
  • Nevirapine / administration & dosage*
  • Nevirapine / adverse effects
  • Pregnancy
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage*
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects
  • Uganda / epidemiology

Substances

  • Anti-HIV Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Nevirapine

Associated data

  • ClinicalTrials.gov/NCT00074412