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

Background

Two 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.

Methods

Postpartum 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.

Results

Pre-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.

Conclusions

Resistance 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.