Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand

© 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: Perinatal single-dose nevirapine (sdNVP) selects for resistance mutations. The objective of this trial was to compare two maternal sdNVP-sparing regimens with standard zidovudine (ZDV)/sdNVP prophylaxis. Design: PHPT-5 was a randomi...

Full description

Saved in:
Bibliographic Details
Main Authors: Marc Lallemant, Sophie Le Coeur, Wasna Sirirungsi, Tim R. Cressey, Nicole Ngo-Giang-Huong, Patrinee Traisathit, Virat Klinbuayaem, Prapan Sabsanong, Prateep Kanjanavikai, Gonzague Jourdain, Kenneth McIntosh, Suporn Koetsawang
Format: Journal
Published: 2018
Subjects:
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84947868974&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/44905
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Chiang Mai University
id th-cmuir.6653943832-44905
record_format dspace
spelling th-cmuir.6653943832-449052018-04-25T07:57:51Z Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand Marc Lallemant Sophie Le Coeur Wasna Sirirungsi Tim R. Cressey Nicole Ngo-Giang-Huong Patrinee Traisathit Virat Klinbuayaem Prapan Sabsanong Prateep Kanjanavikai Gonzague Jourdain Kenneth McIntosh Suporn Koetsawang Agricultural and Biological Sciences © 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: Perinatal single-dose nevirapine (sdNVP) selects for resistance mutations. The objective of this trial was to compare two maternal sdNVP-sparing regimens with standard zidovudine (ZDV)/sdNVP prophylaxis. Design: PHPT-5 was a randomized, partially double-blind placebo-controlled, noninferiority trial in Thailand (NCT00409591). Study participants were women with CD4+ of at least 250 cells/ml and their infants. Methods: All women received ZDV from 28 weeks' gestation and their newborn infants for one week. Women were also randomized to receive NVP-NVP (reference): maternal intrapartum sdNVP with a 7-day 'tail' of ZDV along with lamivudine, and infant NVP (one dose immediately, another 48 h later); infant-only NVP: maternal placebos for sdNVP and the 'tail', with infant NVP; LPV/r: maternal LPV/r starting at 28 weeks. Infants were formula-fed. HIV-diagnosis was determined by DNA-PCR. Results: Four-hundred and thirty-five women were randomized between January 2009 and September 2010. Accrual was terminated prematurely following a change in Thai guidelines recommending antiretroviral combination therapy for all pregnant women. Data on 405 mothers and 407 live-born children were analyzed. Baseline characteristics were similar between arms. Intent-to-treat transmission rates were 3.8% (95% confidence interval: 1.2-8.6) in NVP-NVP, 1.6% (0.2-5.6) in infant-only NVP, and 1.4% (0.4-5.1) in LPV/r arms. As-treated rates were 2.2% (0.5-6.4), 3.2% (0.9-7.9), and 1.5% (0.2-5.2), respectively. Factors independently associated with transmission were prophylaxis duration less than 8 weeks (adjusted odds ratio 15.5; 3.6-66.1) and viral load at baseline at least 4 log10copies/ml (adjusted odds ratio 10.9; 1.3-91.5). Regimens appeared well tolerated. Conclusion: Transmission rates in all arms were low but noninferiority was not proven. Antiretroviral prophylaxis for at least 8 weeks before delivery is necessary to minimize transmission risk. 2018-01-24T04:49:49Z 2018-01-24T04:49:49Z 2015-01-01 Journal 14735571 02699370 2-s2.0-84947868974 10.1097/QAD.0000000000000865 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84947868974&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/44905
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Agricultural and Biological Sciences
spellingShingle Agricultural and Biological Sciences
Marc Lallemant
Sophie Le Coeur
Wasna Sirirungsi
Tim R. Cressey
Nicole Ngo-Giang-Huong
Patrinee Traisathit
Virat Klinbuayaem
Prapan Sabsanong
Prateep Kanjanavikai
Gonzague Jourdain
Kenneth McIntosh
Suporn Koetsawang
Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand
description © 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: Perinatal single-dose nevirapine (sdNVP) selects for resistance mutations. The objective of this trial was to compare two maternal sdNVP-sparing regimens with standard zidovudine (ZDV)/sdNVP prophylaxis. Design: PHPT-5 was a randomized, partially double-blind placebo-controlled, noninferiority trial in Thailand (NCT00409591). Study participants were women with CD4+ of at least 250 cells/ml and their infants. Methods: All women received ZDV from 28 weeks' gestation and their newborn infants for one week. Women were also randomized to receive NVP-NVP (reference): maternal intrapartum sdNVP with a 7-day 'tail' of ZDV along with lamivudine, and infant NVP (one dose immediately, another 48 h later); infant-only NVP: maternal placebos for sdNVP and the 'tail', with infant NVP; LPV/r: maternal LPV/r starting at 28 weeks. Infants were formula-fed. HIV-diagnosis was determined by DNA-PCR. Results: Four-hundred and thirty-five women were randomized between January 2009 and September 2010. Accrual was terminated prematurely following a change in Thai guidelines recommending antiretroviral combination therapy for all pregnant women. Data on 405 mothers and 407 live-born children were analyzed. Baseline characteristics were similar between arms. Intent-to-treat transmission rates were 3.8% (95% confidence interval: 1.2-8.6) in NVP-NVP, 1.6% (0.2-5.6) in infant-only NVP, and 1.4% (0.4-5.1) in LPV/r arms. As-treated rates were 2.2% (0.5-6.4), 3.2% (0.9-7.9), and 1.5% (0.2-5.2), respectively. Factors independently associated with transmission were prophylaxis duration less than 8 weeks (adjusted odds ratio 15.5; 3.6-66.1) and viral load at baseline at least 4 log10copies/ml (adjusted odds ratio 10.9; 1.3-91.5). Regimens appeared well tolerated. Conclusion: Transmission rates in all arms were low but noninferiority was not proven. Antiretroviral prophylaxis for at least 8 weeks before delivery is necessary to minimize transmission risk.
format Journal
author Marc Lallemant
Sophie Le Coeur
Wasna Sirirungsi
Tim R. Cressey
Nicole Ngo-Giang-Huong
Patrinee Traisathit
Virat Klinbuayaem
Prapan Sabsanong
Prateep Kanjanavikai
Gonzague Jourdain
Kenneth McIntosh
Suporn Koetsawang
author_facet Marc Lallemant
Sophie Le Coeur
Wasna Sirirungsi
Tim R. Cressey
Nicole Ngo-Giang-Huong
Patrinee Traisathit
Virat Klinbuayaem
Prapan Sabsanong
Prateep Kanjanavikai
Gonzague Jourdain
Kenneth McIntosh
Suporn Koetsawang
author_sort Marc Lallemant
title Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand
title_short Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand
title_full Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand
title_fullStr Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand
title_full_unstemmed Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand
title_sort randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal hiv in thailand
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84947868974&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/44905
_version_ 1681422646275735552