Marc Lallemant1,2,3, Billy Amzal1,4, Patumrat Sripan1,5,6, Saïk Urien7,8, Tim R Cressey1,2,3, Nicole Ngo-Giang-Huong1,2,3, Virat Klinbuayaem9, Boonsong Rawangban10, Prapan Sabsanong11, Thitiporn Siriwachirachai12, Tapnarong Jarupanich13, Prateep Kanjanavikai14, Phaiboon Wanasiri15, Suporn Koetsawang16, Gonzague Jourdain1,2,3, Sophie Le Coeur1,2,17. 1. Institut de Recherche pour le Développement (IRD) U174/PHPT, Marseille, France. 2. Harvard T.H. Chan School of Public Health, Immunology and Infectious Diseases, Boston, MA. 3. Chiang Mai University, Faculty of Associated Medical Sciences, Chiang Mai, Thailand. 4. LASER Analytica, London, United Kingdom. 5. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 6. URC Paris Centre Necker Cochin, Paris, France. 7. Department of Statistics, Kasetsart University, Faculty of Science, Bangkok, Thailand. 8. Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand. 9. Ministry of Public Health, Sanpatong Hospital, Sanpatong, Thailand. 10. Ministry of Public Health, Nopparat Rajathanee Hospital, Bangkok, Thailand. 11. Ministry of Public Health, Samutprakarn Hospital, Samutprakarn, Thailand. 12. Ministry of Public Health, Khon Kaen Hospital, Khon Kaen, Thailand. 13. Ministry of Public Health, Hat Yai Hospital, Hat Yai, Thailand. 14. Ministry of Public Health, Banglamung Hospital, Chonburi, Thailand. 15. Ministry of Public Health, Kalasin Hospital, Kalasin, Thailand. 16. Mahidol University, Family Health Research Center, Bangkok, Thailand; and. 17. Mortality, Health and Epidemiology Unit, Institut National d'Etudes Démographiques (INED), Paris, France.
Abstract
INTRODUCTION: Infants born to women living with HIV initiating combination antiretroviral therapy (cART) late in pregnancy are at high risk of intrapartum infection. Mother/infant perinatal antiretroviral intensification may substantially reduce this risk. METHODS: In this single-arm Bayesian trial, pregnant women with HIV receiving standard of care antiretroviral prophylaxis in Thailand (maternal antenatal lopinavir-based cART; nonbreastfed infants 4 weeks' postnatal zidovudine) were offered "antiretroviral intensification" (labor single-dose nevirapine plus infant zidovudine-lamivudine-nevirapine for 2 weeks followed by zidovudine-lamivudine for 2 weeks) if their antenatal cART was initiated ≤8 weeks before delivery. A negative birth HIV-DNA polymerase chain reaction (PCR) followed by a confirmed positive PCR defined intrapartum transmission. Before study initiation, we modeled intrapartum transmission probabilities using data from 3738 mother/infant pairs enrolled in our previous trials in Thailand using a logistic model, with perinatal maternal/infant antiretroviral regimen and predicted viral load at delivery as main covariates. Using the characteristics of the women enrolled who received intensification, prior intrapartum transmission probabilities (credibility intervals) with/without intensification were estimated. After including the transmission data observed in the current study, the corresponding Bayesian posterior transmission probability was derived. RESULTS: No intrapartum transmission of HIV was observed among the 88 mother/infant pairs receiving intensification. The estimated intrapartum transmission probability was 2·2% (95% credibility interval 0·5-6·1) without intensification versus 0·3% (0·0-1·6) with intensification. The probability of superiority of intensification over standard of care was 94·4%. Antiretroviral intensification appeared safe. CONCLUSION: Mother/infant antiretroviral intensification was effective in preventing intrapartum transmission of HIV in pregnant women receiving ≤8 weeks antepartum cART.
INTRODUCTION:Infants born to women living with HIV initiating combination antiretroviral therapy (cART) late in pregnancy are at high risk of intrapartum infection. Mother/infant perinatal antiretroviral intensification may substantially reduce this risk. METHODS: In this single-arm Bayesian trial, pregnant women with HIV receiving standard of care antiretroviral prophylaxis in Thailand (maternal antenatal lopinavir-based cART; nonbreastfed infants 4 weeks' postnatal zidovudine) were offered "antiretroviral intensification" (labor single-dose nevirapine plus infantzidovudine-lamivudine-nevirapine for 2 weeks followed by zidovudine-lamivudine for 2 weeks) if their antenatal cART was initiated ≤8 weeks before delivery. A negative birth HIV-DNA polymerase chain reaction (PCR) followed by a confirmed positive PCR defined intrapartum transmission. Before study initiation, we modeled intrapartum transmission probabilities using data from 3738 mother/infant pairs enrolled in our previous trials in Thailand using a logistic model, with perinatal maternal/infant antiretroviral regimen and predicted viral load at delivery as main covariates. Using the characteristics of the women enrolled who received intensification, prior intrapartum transmission probabilities (credibility intervals) with/without intensification were estimated. After including the transmission data observed in the current study, the corresponding Bayesian posterior transmission probability was derived. RESULTS: No intrapartum transmission of HIV was observed among the 88 mother/infant pairs receiving intensification. The estimated intrapartum transmission probability was 2·2% (95% credibility interval 0·5-6·1) without intensification versus 0·3% (0·0-1·6) with intensification. The probability of superiority of intensification over standard of care was 94·4%. Antiretroviral intensification appeared safe. CONCLUSION: Mother/infant antiretroviral intensification was effective in preventing intrapartum transmission of HIV in pregnant women receiving ≤8 weeks antepartum cART.