Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated.

Publication Type:

Journal Article

Source:

AIDS (London, England), Volume 26, Issue 3, p.325-333 (2012)

Keywords:

2012, Adult, Anemia, Anti-HIV Agents, Blotting, Western, Breast Feeding, Center-Authored Paper, December 2011, Drug Administration Schedule, Drug Eruptions, Exanthema, Female, HIV Seropositivity, HIV-1, Humans, Infant, Infant, Newborn, Infectious Disease Transmission, Vertical, Male, Milk, Human, NEUTROPENIA, Nevirapine, PREGNANCY, Risk Factors, Time Factors, Treatment Outcome, Trimethoprim-Sulfamethoxazole Combination, Uganda, Vaccine and Infectious Disease Division

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.