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.
aMakerere University, Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda
bDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
cStatistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington
dWake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, United States
eUniversity of Zimbabwe College of Health Sciences, Harare, Zimbabwe
fThe Vaccine and Infectious Diseases and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center (FHCRC), Washington, United States of America
gMaternal Adolescent and Child Health (MatCH), University of the Witwatersrand
hNelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Correspondence to Jim Aizire, MBCHB, MHS (Epi), Investigator, Makerere University, Johns Hopkins University Research Collaboration, MU-JHU Research Building, Old Mulago Hill Road, 23491 Kampala, Uganda. Tel: +256 414 541 044; fax: +256 414 543 002; e-mail: email@example.com
Received 5 August, 2011
Revised 11 October, 2011
Accepted 25 October, 2011