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

Aizire, Jima; Fowler, Mary Glenna,b; Wang, Jingc; Shetty, Avinash K.d; Stranix-Chibanda, Lyndae; Kamateeka, Moreena; Brown, Elizabeth R.f; Bolton, Steve G.b; Musoke, Philippa M.a; Coovadia, Hooseng,h

doi: 10.1097/QAD.0b013e32834e892c
Clinical Science

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: jaizire@mujhu.org

Received 5 August, 2011

Revised 11 October, 2011

Accepted 25 October, 2011

© 2012 Lippincott Williams & Wilkins, Inc.