A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine

• Main Authors: Van Dyke R., Ngo-Giang-Huong N., Shapiro D., Frenkel L., Britto P., Roongpisuthipong A., Beck I., Yuthavisuthi P., Prommas S., Puthanakit T., Achalapong J., Chotivanich N., Rasri W., Cressey T., Maupin R., Mirochnick M., Jourdain G.
• Format: Journal
• Published: 2017
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84555209220&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/42901
• Institution: Chiang Mai University

Background. Intrapartum single-dose (SD) nevirapine (NVP) reduces perinatal transmission of human immunodeficiency virus (HIV) infection but selects for NVP-resistant virus, which compromises subsequent NVP-based therapy. A 1-week "tail" of lamivudine and zidovudine after SD-NVP decreases the risk of resistance. We hypothesized that increasing the duration or potency of the tail would further reduce this risk to < 10%, using a sensitive assay to measure resistance.Methods.HIV-infected pregnant Thai women with a CD4 cell count > 250 cells/μL, most receiving zidovudine, were randomized at 28-38 weeks gestation to receive 1 of 3 intrapartum and postpartum regimens: (A) zidovudine plus enteric-coated didanosine plus lopinavir and ritonavir for 7 days, (B) zidovudine plus enteric-coated didanosine for 30 days, or (C) regimen 1 for 30 days. The incidence of NVP resistance mutations at day 10 or week 6 post partum in each arm was compared with that of a historical comparison group who received prenatal zidovudine and SD-NVP. NVP resistance was identified by consensus sequencing and a sensitive oligonucleotide ligation assay (OLA). Results. At entry, the 169 participants had a median CD4 cell count of 456 cells/μL and an HIV load of 3.49 log10 copies/mL. The incidence of mutations in each of the 3 P1032 arms was 0% by sequencing and 1.8%, 7.1%, and 5.3% by OLA in arms A, B, and C, respectively, compared with 13.4% by sequencing and 29.4% by OLA in the comparison group (P < . 001 for each study arm vs comparison group). Grade 4 anemia developed in 1 woman.Conclusions.A 7-day tail of highly active combination therapy or 1 month of dual therapy after SD-NVP prevents most NVP resistance to minimal toxicity.Clinical Trials Registration.The IMPAACT P1032 Clinical Trial is NCT00109590, and the PHPT-2 Clinical Trial is NCT00398684. © 2011 The Author.