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

50 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

Nevirapine
Breast Feeding
Parturition
Safety
HIV-1
Mothers
Labor Onset
Human Milk
Neutropenia
Postpartum Period

All Science Journal Classification (ASJC) codes

  • Virology
  • Immunology

Cite this

Shetty, Avinash K. ; Coovadia, Hoosen M. ; Mirochnick, Mark M. ; Maldonado, Yvonne ; Mofenson, Lynne M. ; Eshleman, Susan H. ; Fleming, Thomas ; Emel, Lynda ; George, Kathy ; Katzenstein, David A. ; Wells, Jennifer ; Maponga, Charles C. ; Mwatha, Anthony ; Jones, Samuel Adeniyi ; Karim, Salim S Abdool ; Bassett, Mary T. / Safety and Trough Concentrations of Nevirapine Prophylaxis Given Daily, Twice Weekly, or Weekly in Breast-Feeding Infants from Birth to 6 Months. In: Journal of Acquired Immune Deficiency Syndromes. 2003 ; Vol. 34, No. 5. pp. 482-490.
@article{ad72c94a9585406e882f4c11cf83aa39,
title = "Safety and Trough Concentrations of Nevirapine Prophylaxis Given Daily, Twice Weekly, or Weekly in Breast-Feeding Infants from Birth to 6 Months",
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.",
author = "Shetty, {Avinash K.} and Coovadia, {Hoosen M.} and Mirochnick, {Mark M.} and Yvonne Maldonado and Mofenson, {Lynne M.} and Eshleman, {Susan H.} and Thomas Fleming and Lynda Emel and Kathy George and Katzenstein, {David A.} and Jennifer Wells and Maponga, {Charles C.} and Anthony Mwatha and Jones, {Samuel Adeniyi} and Karim, {Salim S Abdool} and Bassett, {Mary T.}",
year = "2003",
month = "12",
day = "15",
doi = "10.1097/00126334-200312150-00006",
language = "English",
volume = "34",
pages = "482--490",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

Shetty, AK, Coovadia, HM, Mirochnick, MM, Maldonado, Y, Mofenson, LM, Eshleman, SH, Fleming, T, Emel, L, George, K, Katzenstein, DA, Wells, J, Maponga, CC, Mwatha, A, Jones, SA, Karim, SSA & Bassett, MT 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, vol. 34, no. 5, pp. 482-490. https://doi.org/10.1097/00126334-200312150-00006

Safety and Trough Concentrations of Nevirapine Prophylaxis Given Daily, Twice Weekly, or Weekly in Breast-Feeding Infants from Birth to 6 Months. / Shetty, Avinash K.; Coovadia, Hoosen M.; Mirochnick, Mark M.; Maldonado, Yvonne; Mofenson, Lynne M.; Eshleman, Susan H.; Fleming, Thomas; Emel, Lynda; George, Kathy; Katzenstein, David A.; Wells, Jennifer; Maponga, Charles C.; Mwatha, Anthony; Jones, Samuel Adeniyi; Karim, Salim S Abdool; Bassett, Mary T.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 34, No. 5, 15.12.2003, p. 482-490.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Safety and Trough Concentrations of Nevirapine Prophylaxis Given Daily, Twice Weekly, or Weekly in Breast-Feeding Infants from Birth to 6 Months

AU - Shetty, Avinash K.

AU - Coovadia, Hoosen M.

AU - Mirochnick, Mark M.

AU - Maldonado, Yvonne

AU - Mofenson, Lynne M.

AU - Eshleman, Susan H.

AU - Fleming, Thomas

AU - Emel, Lynda

AU - George, Kathy

AU - Katzenstein, David A.

AU - Wells, Jennifer

AU - Maponga, Charles C.

AU - Mwatha, Anthony

AU - Jones, Samuel Adeniyi

AU - Karim, Salim S Abdool

AU - Bassett, Mary T.

PY - 2003/12/15

Y1 - 2003/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0345059380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345059380&partnerID=8YFLogxK

U2 - 10.1097/00126334-200312150-00006

DO - 10.1097/00126334-200312150-00006

M3 - Article

VL - 34

SP - 482

EP - 490

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 5

ER -