Clinical SciencePerinatal Antiretroviral Intensification to Prevent Intrapartum HIV Transmission When Antenatal Antiretroviral Therapy Is Initiated Less Than 8 Weeks Before DeliveryLallemant, Marc MDa,b,c; Amzal, Billy PhDa,d; Sripan, Patumrat PhDa,e,f; Urien, Saïk PhDg,h; Cressey, Tim R. PhDa,b,c; Ngo-Giang-Huong, Nicole PhDa,b,c; Klinbuayaem, Virat MDi; Rawangban, Boonsong MDj; Sabsanong, Prapan MDk; Siriwachirachai, Thitiporn MDl; Jarupanich, Tapnarong MDm; Kanjanavikai, Prateep MDn; Wanasiri, Phaiboon MDo; Koetsawang, Suporn MDp; Jourdain, Gonzague MDa,b,c; Le Coeur, Sophie MDa,b,q, on behalf of the PHPT-5 site investigatorsAuthor Information aInstitut de Recherche pour le Développement (IRD) U174/PHPT, Marseille, France; bHarvard T.H. Chan School of Public Health, Immunology and Infectious Diseases, Boston, MA; cChiang Mai University, Faculty of Associated Medical Sciences, Chiang Mai, Thailand; dLASER Analytica, London, United Kingdom; eDepartment of Statistics, Kasetsart University, Faculty of Science, Bangkok, Thailand; fResearch Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; gUniversité Paris Descartes, Sorbonne Paris Cité, Paris, France; hURC Paris Centre Necker Cochin, Paris, France; iMinistry of Public Health, Sanpatong Hospital, Sanpatong, Thailand; jMinistry of Public Health, Nopparat Rajathanee Hospital, Bangkok, Thailand; kMinistry of Public Health, Samutprakarn Hospital, Samutprakarn, Thailand; lMinistry of Public Health, Khon Kaen Hospital, Khon Kaen, Thailand; mMinistry of Public Health, Hat Yai Hospital, Hat Yai, Thailand; nMinistry of Public Health, Banglamung Hospital, Chonburi, Thailand; oMinistry of Public Health, Kalasin Hospital, Kalasin, Thailand; pMahidol University, Family Health Research Center, Bangkok, Thailand; and qMortality, Health and Epidemiology Unit, Institut National d'Etudes Démographiques (INED), Paris, France. Correspondence to: Marc Lallemant, MD, IRD174-PHPT, 195 Kaew Nawarat Road (3-4 Fl) Wat Ked, Muang Chiang Mai, 50000 Thailand (e-mail: email@example.com). Supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), USA (Grant number R01 HD052461 and R01 HD056953); the Ministry of Public Health, Thailand; the Institut de Recherche pour le Développement, France; the Institut National d’Etudes Démographiques, France; and the Thailand International Development Cooperation Agency (TICA). GlaxoSmithKline and Boehringer Ingelheim provided study drugs for the historical clinical trials that were meta-analyzed and this study. The authors have no funding or conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com). PHPT-5 site investigators are listed in the Acknowledgment section. JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1, 2020 - Volume 84 - Issue 3 - p 313-322 doi: 10.1097/QAI.0000000000002350 Buy SDC Metrics 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.