Pharmacokinetics and virologic response of zidovudine/lopinavir/ritonavir initiated during the third trimester of pregnancy
Tim R Cressey, Gonzague Jourdain, Boonsong Rawangban, Supang Varadisai, Rucha Kongpanichkul, Prapan Sabsanong, Prapap Yuthavisuthi, Somnuk Chirayus, Nicole Ngo-Giang-Huong, Nipunporn Voramongkol, Somsak Pattarakulwanich, Marc Lallemant, PHPT-5 Team, Jittapol Hemvuttiphan, Ruethai Wongchai, Borwornluck Changlor, Ampai Maneekaew, Kunlaya Jansook, Saowakhon Bunchaisun, Jullapong Achalapong, Subenya Jinasa, Purivis Chart, Kannikar Saisawat, Pollawat Thongsuk, Supaporn Utsaha, Sudanee Buranabanjasatean, Natjaree Thuenyeanyong, Phithak Kaeha, Thanutra Taiyaithieng, Benjaporn Juntapoon, Prapap Yuthavisuthi, Renoo Wongsrisai, Ubon Chanasit, Nuttupassasorn Tungtongcha, Pisut Greetanukroh, Kamol Boonrod, Suchada Thongsuwan, Prateep Kanjanavikai, Watcharin Kaewsaweat, Sarocha Sawatmarn, Nantasak Chotivanich, Tiwacha Thimakam, Nusara Krapunpongsakul, Chanida Asarath, Raewadee Wanno, Prakit Yothipitak, Suluck Soontaros, Kessarin Chaisiri, Weerapong Suwankornsakul, Phatcharin Thuraset, Arthit Cheawchan, Sukonta Phasuk, Aram Limtrakul, Janjira Thonglo, Benjawan Thomyota, Autcharaporn Nakrit, Pusdee Lymthavorn, Boonsong Rawangban, Patcharaporn Krueduangkam, Thamon Wijitwong, Kantinan Leepaiboon, Pranom Poolpat, Sinart Prommas, Marina Thitathan, Santi Winaitham, Boonruen Pengmark, Surachai Pipatnakulchai, Jiradsadaporn Khanmali, Kesorn Jitmaleerat, Kingtong Wongsirikul, Tapnarong Jarupanich, Namthip Kruenual, Usa Sukhaphan, Raruay Jitsakulchaidej, Noossara Puarattana, Waropart Pongchaisit, Sinnapa Pothinukka, Nunthiya Phomcheam, Supattra Kaengklang, Supang Varadisai, Jantra Chalasin, Yaowalak Sookbumrung, Wilai Raiva, Rucha Kongpanichkul, Chutima Seema, Parawan Bunditwong, Panita Kapol, Prapan Sabsanong, Boonyavee Ratchanee, Kedsara Bunluesak, Arun Yaisiri, Noupporn Jenpoomjai, Prateung Lianpongsabuddhi, Sirirat Thammajitsagul, Tiemjan Keowkarnkah, Sasipun Supong, Sunee Hanyutthapong, Wanpen Leelaporn, Somnuk Chirayus, Sompong Wannun, Sudtida Eawsakul, Iriyaporn Kongthap, Nuttharee Pinkaew, Boonrak Wiriyachoke, Chisakan Thanadechworasate, Punjamaporn Satjeanphong, Ratchadaporn Katekaraj, Manoch Chakorngowit, Somsong Niamlamul, Samapond Saithong, Parinee Suebchart, Siripon Kanshana, Suporn Koetsawang, Sophie Le Coeur, Ken McIntosh, Pra-ornsuda Sukrakanchana, Suwalai Chalermpantmetagul, Kanchana Than-in-at, Yardpiron Taworn, Pimpinun Punyati, Angkana Thongkum, Paporn Mongkolwat, Ampika Kaewbundit, Panida Pongpunyayuen, Luc Decker, Aksorn Lueanyod, Suriyan Tanasri, Sanupong Chailert, Kanjana Yoddee, Rungruangrong Seubmongkolchai, Dujrudee Chinwong, Pongpreeda Saenchitta, Chalermpong Sanjoom, Tim R Cressey, Gonzague Jourdain, Boonsong Rawangban, Supang Varadisai, Rucha Kongpanichkul, Prapan Sabsanong, Prapap Yuthavisuthi, Somnuk Chirayus, Nicole Ngo-Giang-Huong, Nipunporn Voramongkol, Somsak Pattarakulwanich, Marc Lallemant, PHPT-5 Team, Jittapol Hemvuttiphan, Ruethai Wongchai, Borwornluck Changlor, Ampai Maneekaew, Kunlaya Jansook, Saowakhon Bunchaisun, Jullapong Achalapong, Subenya Jinasa, Purivis Chart, Kannikar Saisawat, Pollawat Thongsuk, Supaporn Utsaha, Sudanee Buranabanjasatean, Natjaree Thuenyeanyong, Phithak Kaeha, Thanutra Taiyaithieng, Benjaporn Juntapoon, Prapap Yuthavisuthi, Renoo Wongsrisai, Ubon Chanasit, Nuttupassasorn Tungtongcha, Pisut Greetanukroh, Kamol Boonrod, Suchada Thongsuwan, Prateep Kanjanavikai, Watcharin Kaewsaweat, Sarocha Sawatmarn, Nantasak Chotivanich, Tiwacha Thimakam, Nusara Krapunpongsakul, Chanida Asarath, Raewadee Wanno, Prakit Yothipitak, Suluck Soontaros, Kessarin Chaisiri, Weerapong Suwankornsakul, Phatcharin Thuraset, Arthit Cheawchan, Sukonta Phasuk, Aram Limtrakul, Janjira Thonglo, Benjawan Thomyota, Autcharaporn Nakrit, Pusdee Lymthavorn, Boonsong Rawangban, Patcharaporn Krueduangkam, Thamon Wijitwong, Kantinan Leepaiboon, Pranom Poolpat, Sinart Prommas, Marina Thitathan, Santi Winaitham, Boonruen Pengmark, Surachai Pipatnakulchai, Jiradsadaporn Khanmali, Kesorn Jitmaleerat, Kingtong Wongsirikul, Tapnarong Jarupanich, Namthip Kruenual, Usa Sukhaphan, Raruay Jitsakulchaidej, Noossara Puarattana, Waropart Pongchaisit, Sinnapa Pothinukka, Nunthiya Phomcheam, Supattra Kaengklang, Supang Varadisai, Jantra Chalasin, Yaowalak Sookbumrung, Wilai Raiva, Rucha Kongpanichkul, Chutima Seema, Parawan Bunditwong, Panita Kapol, Prapan Sabsanong, Boonyavee Ratchanee, Kedsara Bunluesak, Arun Yaisiri, Noupporn Jenpoomjai, Prateung Lianpongsabuddhi, Sirirat Thammajitsagul, Tiemjan Keowkarnkah, Sasipun Supong, Sunee Hanyutthapong, Wanpen Leelaporn, Somnuk Chirayus, Sompong Wannun, Sudtida Eawsakul, Iriyaporn Kongthap, Nuttharee Pinkaew, Boonrak Wiriyachoke, Chisakan Thanadechworasate, Punjamaporn Satjeanphong, Ratchadaporn Katekaraj, Manoch Chakorngowit, Somsong Niamlamul, Samapond Saithong, Parinee Suebchart, Siripon Kanshana, Suporn Koetsawang, Sophie Le Coeur, Ken McIntosh, Pra-ornsuda Sukrakanchana, Suwalai Chalermpantmetagul, Kanchana Than-in-at, Yardpiron Taworn, Pimpinun Punyati, Angkana Thongkum, Paporn Mongkolwat, Ampika Kaewbundit, Panida Pongpunyayuen, Luc Decker, Aksorn Lueanyod, Suriyan Tanasri, Sanupong Chailert, Kanjana Yoddee, Rungruangrong Seubmongkolchai, Dujrudee Chinwong, Pongpreeda Saenchitta, Chalermpong Sanjoom
Abstract
Objective: To evaluate the pharmacokinetics and HIV viral load response following initiation during the third trimester of pregnancy of zidovudine plus standard-dose lopinavir boosted with ritonavir (LPV/r), twice daily, until delivery for the prevention of mother-to-child transmission of HIV.
Design: Prospective study nested within a multicenter, three-arm, randomized, phase III prevention of mother-to-child transmission of HIV trial in Thailand (PHPT-5, ClinicalTrials.gov Identifier: NCT00409591).
Methods: Women randomized to receive 300 mg zidovudine and 400/100 mg LPV/r twice daily from 28 weeks' gestation, or as soon as possible thereafter, until delivery had intensive steady-state 12-h blood sampling performed. LPV/r pharmacokinetic parameters were calculated using noncompartmental analysis. Rules were defined a priori for a LPV/r dose escalation based on the proportion of women with an LPV area under the concentration-time curve (AUC) below 52 microg h/ml (10th percentile for LPV AUC in nonpregnant adults). HIV-1 RNA response was assessed during the third trimester.
Results: Thirty-eight women were evaluable; at entry, median (range) gestational age was 29 (28-36) weeks, weight 59.5 (45.0-91.6) kg, CD4 cells count 442 (260-1327) cells/microl and HIV-1 RNA viral load 7818 (<40-402 015) copies/ml. Geometric mean (90% confidence interval) LPV AUC, Cmax and Cmin were 64.6 (59.7-69.8) microg h/ml, 8.1 (7.5-8.7) microg/ml and 2.7 (2.4-3.0) microg/ml, respectively. Thirty-one of 38 (81%) women had an LPV AUC above the AUC target. All women had a HIV-1 viral load less than 400 copies/ml at the time of delivery.
Conclusion: A short course of zidovudine plus standard-dose LPV/r initiated during the third trimester of pregnancy achieved adequate LPV exposure and virologic response.
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Source: PubMed