Randomized trial of stopping or continuing ART among postpartum women with pre-ART CD4 ≥ 400 cells/mm³

• Main Authors: Judith S. Currier, Paula Britto, Risa M. Hoffman, Sean Brummel, Gaerolwe Masheto, Esau Joao, Breno Santos, Linda Aurpibul, Marcelo Losso, Marie F. Pierre, Adriana Weinberg, Devasena Gnanashanmugam, Nahida Chakhtoura, Karin Klingman, Renee Browning, Anne Coletti, Lynne Mofenson, David Shapiro, Jose Pilotto, Manuela Bullo, Silvina Ivalo, Anthony Ogwu, Tebogo Kakhu, Aida Asmelash, Ayotunde Omoz-Oarhe, Cristina Hofer, Elizabeth MacHado, Jacqueline Menezes, Leon Claude Sidi, Jorge Pinto, Flavia Ferreira, Geraldo Duarte, Conrado Milani Coutinho, Rosa Dea Sperhacke, Silvia Mariani Costamilan, Luis Eduardo Fernandes, Luiz Felipe Mpreira, Regis Kreitchmann, Debora Fernandes Coelho, Marineide Goncalves De Melo, Rita De Cassia Alves Lira, Linda Aristhomene, Jerry Bonhomme, Rosa Infante, Fanny Rosas, Esmelda Montalban, Jessica Rios, Julkanya Chokephaibulkit, Thanomsak Anekthananon, Jullapong Achalapong, Pacharee Kantipong, Guttiga Halue, Wirawan Rasri, Prapap Yuthavisuthi, Malee Techapornroong, Sinart Prommas, Prapaisri Layangool, Chureeratana Bowonwatanuwong, Nantasak Chotivanich, Fuanglada Tongprasert, Patcharaphan Sugandhavesa, Vanessa Cajahuaringa, Renee Weinman, Sara Mattiucci, Princy Kumar, Joseph Timpone, Chivon McMullen-Jackson, Shelley Buschur
• Format: Journal
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85019102777&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/46222
• Institution: Chiang Mai University

Background Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. Methods Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm 3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen. The sample size was selected to provide 88% power to detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2 and 3 events. All analyses were intent to treat. Results 1652 women from 52 sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US were enrolled (1/2010-11/2014). Median age was 28 years and major racial categories were Black African (28%), Asian (25%) White (15%). Median entry CD4 count was 696 cells/mm 3 (IQR 575±869), median ART exposure prior to delivery was 19 weeks (IQR 13± 24) and 94% had entry HIV-1 RNA < 1000 copies/ml. After a median follow-up of 2.3 years, the primary composite endpoint rate was significantly lower than expected, and not significantly different between arms (continue arm 0.21 /100 person years(py); discontinue 0.31/ 100 py, Hazard ratio (HR) 0.68, 95% CI: 0.19, 2.40). WHO Stage 2 and 3 events were significantly reduced with continued ART (2.08/100 py vs. 4.36/100 py in the discontinue arm; HR 0.48, 95%CI: 0.33, 0.70). Toxicity rates did not differ significantly between arms. Among women randomized to continue ART, 189/827 (23%) had virologic failure; of the 155 with resistance testing, 103 (66%) failed without resistance to their current regimen, suggesting non-adherence. Conclusions Overall, serious clinical events were rare among young HIV-positive post-partum women with high CD4 cell counts. Continued ART was safe and was associated with a halving of the rate of WHO 2/3 conditions. Virologic failure rates were high, underscoring the urgent need to improve adherence in this population. Trial registration ClinicalTrials.gov NCT00955968.