Impact of Human Immunodeficiency Virus Drug Resistance Mutations Detected in Women Prior to Antiretroviral Therapy With Efavirenz + Tenofovir Disoproxil Fumarate + Lamivudine (or Emtricitabine)
Authors: Boyce Ceejay L , Sils Tatiana , Milne Ross S , Wallner Jackson J , Hardy Samantha R , Ko Daisy , Wong-On-Wing Annie , Mackey Malia , Higa Nikki , Beck Ingrid A , Styrchak Sheila M , DeMarrais Patricia , Tierney Camlin , Fowler Mary G , Frenkel Lisa M ,   Promoting Maternal and Infant Survival Everywhere (PROMISE) Study Team, Flynn Patricia M , Currier Judith , Fiscus Susan , Luzuriaga Katherine , Weinberg Adriana , McIntyre James , Chipato Tsungai , Fox Lawrence , Klingman Karin L , Browning Renee , Mofenson Lynne M , Siberry George K , Watts Heather , Purdue Lynette , Shapiro David , Fenton Terrence , Cababasay Mae P , Britto Paula , Wang Yan , Liu Li , Brummel Sean , Angelidou Konstantia , Basar Michael , Millar Linda , Kaiser Kathleen , Gaeddert John , Marillo Linda , Ciaranello Andrea , Freedberg Kenneth , Barlow-Mosha Linda , Toye Mary Patricia , Mirochnick Mark , Bhattacharya Debika , Jennings Amy , Manzella Adam , Zadzilka Amanda , Kabat William B , Loftis Amy James , Chi Benjamin , Lallemant Marc , Taha Taha E , Moodley Dhayendre , Nielsen Karin , Bardeguez Arlene , Coutsoudis Anna , Gupta Amita , Hoffman Risa , McFarland Elizabeth , Stranix-Chibanda Lynda , Theron Gerhard B , Msweli Lindiwe , Coletti Anne , George Kathleen , Valentine Megan , Martinez Marisol , Rooney James F , Ivanova Oxana , Porter Danielle Poulin , Snowden Wendy , Watson Helen , Moultrie Harry , Coovadia Ashraf , Strehlau Renate , Theron Gerhard B , Cotton Mark , Rossouw Magdel , Bobat Raziya , Sebitloane Motshidi , Moodley Dhayendre , Violari Avy , Kamthunzi Portia , Hosseinipour Mina , Kumwenda Newton , Mallewa Mac , Mlay Pendo , Buchanan Anne , Chintu Namwinga , Mubiana-Mbewe Mwangelwa , Owor Maxensia , Aizire Jim , Chipato Tsungai , Bhosale Ramesh , Khadse Sandhya 
Published: July 2024

AbstractBackgroundTwo large studies suggest that resistance mutations to only nonnucleoside reverse transcriptase inhibitors (NNRTI) did not increase the risk of virologic failure during antiretroviral therapy (ART) with efavirenz/tenofovir disoproxil fumarate/lamivudine (or emtricitabine). We retrospectively evaluated a third cohort to determine the impact of NNRTI resistance on the efficacy of efavirenz-based ART.MethodsPostpartum women living with human immunodeficiency virus (HIV) were studied if they initiated efavirenz-based ART because of the World Health Organization’s recommendation for universal ART. Resistance was detected by Sanger genotyping plasma prior to efavirenz-based ART and at virologic failure (HIV RNA &gt;400 copies/mL). Logistic regression examined relationships between pre-efavirenz genotypes and virologic failure.ResultsPre-efavirenz resistance was detected in 169 of 1223 (13.8%) participants. By month 12 of efavirenz-based ART, 189 of 1233 (15.3%) participants had virologic failure. Rates of virologic failure did not differ by pre-efavirenz NNRTI resistance. However, while pre-efavirenz nucleos(t)ide reverse transcriptase inhibitors (NRTI) and NNRTI resistance was rare (8/1223 [0.7%]) this genotype increased the odds (adjusted odds ratio, 11.2 [95% confidence interval, 2.21–72.2]) of virologic failure during efavirenz-based ART. Age, time interval between last viremic visit and efavirenz initiation, clinical site, viremia at delivery, hepatitis B virus coinfection, and antepartum regimen were also associated with virologic failure.ConclusionsResistance to NNRTI alone was prevalent and dual-class (NRTI and NNRTI) resistance was rare in this cohort, with only the latter associated with virologic failure. This confirms others’ findings that, if needed, efavirenz-based ART offers most people an effective alternative to dolutegravir-based ART.