Safety and Trough Concentrations of Nevirapine Prophylaxis Given Daily, Twice Weekly, or Weekly in Breast-Feeding Infants from Birth to 6 Months

Avinash K. Shetty, Hoosen M. Coovadia, Mark M. Mirochnick, Yvonne Maldonado, Lynne M. Mofenson, Susan H. Eshleman, Thomas Fleming, Lynda Emel, Kathy George, David A. Katzenstein, Jennifer Wells, Charles C. Maponga, Anthony Mwatha, Samuel Adeniyi Jones, Salim S Abdool Karim, Mary T. Bassett

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Despite the success of antiretroviral prophylaxis in reducing mother-to-child HIV-1 transmission, postpartum transmission through breast milk remains a problem. Antiretroviral administration to the infant during the period of breast-feeding could protect against postnatal transmission. An open-label phase 1/2 study was designed to assess the safety and trough concentrations of nevirapine (NVP) given once weekly (OW), twice weekly (TW), or once daily (OD) to HIV-exposed breast-feeding infants for 24 weeks. Following maternal dosing with 200 mg NVP orally at onset of labor, breast-feeding infants were randomized within 48 hours of birth to 1 of 3 regimens: arm 1, NVP given OW (4 mg/kg from birth to 14 days, ↑ to 8 mg/kg from 15 days to 24 weeks), arm 2, NVP given TW (4 mg/kg from birth to 14 days, ↑ to 8 mg/kg from 15 days to 24 weeks), and arm 3, NVP given OD (2 mg/kg from birth to 14 days, ↑ to 4 mg/kg from 15 days to 24 weeks). Trough NVP concentrations and clinical and laboratory abnormalities were monitored. Of the 75 infants randomized (26 to OW, 25 to TW, and 24 to OD dosing), 63 completed the 32-week follow-up visit. No severe skin, hepatic, or renal toxicity related to NVP was observed. Neutropenia occurred in 8 infants. Trough NVP levels were lower than the therapeutic target (100 ng/mL) in 48 of 75 (64.0%) samples from infants in the OW arm, 3 of 65 (4.6%) samples in the TW arm, and 0 of 72 samples in the OD arm. Median (range) trough NVP concentrations were 64 ng/mL (range: <25-1519 ng/mL) with OW dosing; 459 (range: <25-1386 ng/mL) with TW dosing; and 1348 (range: 108-4843 ng/ml) with OD dosing. Our data indicate that NVP prophylaxis for 6 months was safe and well tolerated in infants. OD NVP dosing resulted in all infants with trough concentration greater than the therapeutic target and maintenance of high drug concentrations. A phase 3 study is planned to assess the efficacy of OD infant NVP regimen to prevent breast-feeding HIV-1 transmission.

Original languageEnglish
Pages (from-to)482-490
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume34
Issue number5
DOIs
Publication statusPublished - 15-12-2003
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Virology
  • Immunology

Cite this

Shetty, A. K., Coovadia, H. M., Mirochnick, M. M., Maldonado, Y., Mofenson, L. M., Eshleman, S. H., Fleming, T., Emel, L., George, K., Katzenstein, D. A., Wells, J., Maponga, C. C., Mwatha, A., Jones, S. A., Karim, S. S. A., & Bassett, M. T. (2003). Safety and Trough Concentrations of Nevirapine Prophylaxis Given Daily, Twice Weekly, or Weekly in Breast-Feeding Infants from Birth to 6 Months. Journal of Acquired Immune Deficiency Syndromes, 34(5), 482-490. https://doi.org/10.1097/00126334-200312150-00006