Impact of Human Immunodeficiency Virus Drug Resistance Mutations Detected in Women Prior to Antiretroviral Therapy With Efavirenz + Tenofovir Disoproxil Fumarate + Lamivudine (or Emtricitabine)

Ceejay L Boyce; Tatiana Sils; Ross S Milne; Jackson J Wallner; Samantha R Hardy; Daisy Ko; Annie Wong-On-Wing; Malia Mackey; Nikki Higa; Ingrid A Beck; Sheila M Styrchak; Patricia DeMarrais; Camlin Tierney; Mary G Fowler; Lisa M Frenkel; Promoting Maternal and Infant Survival Everywhere (PROMISE) Study Team

doi:10.1093/ofid/ofae383

Impact of Human Immunodeficiency Virus Drug Resistance Mutations Detected in Women Prior to Antiretroviral Therapy With Efavirenz + Tenofovir Disoproxil Fumarate + Lamivudine (or Emtricitabine)

Open Forum Infect Dis. 2024 Jul 15;11(7):ofae383. doi: 10.1093/ofid/ofae383. eCollection 2024 Jul.

Authors

Ceejay L Boyce^{1

2}, Tatiana Sils², Ross S Milne², Jackson J Wallner², Samantha R Hardy², Daisy Ko², Annie Wong-On-Wing², Malia Mackey², Nikki Higa², Ingrid A Beck², Sheila M Styrchak², Patricia DeMarrais³, Camlin Tierney³, Mary G Fowler⁴, Lisa M Frenkel^{1

2

5

6}; Promoting Maternal and Infant Survival Everywhere (PROMISE) Study Team

Collaborators

Promoting Maternal and Infant Survival Everywhere (PROMISE) Study Team:
Patricia M Flynn, Judith Currier, Susan Fiscus, Katherine Luzuriaga, Adriana Weinberg, James McIntyre, Tsungai Chipato, Lawrence Fox, Karin L Klingman, Renee Browning, Lynne M Mofenson, George K Siberry, Heather Watts, Lynette Purdue, David Shapiro, Terrence Fenton, Mae P Cababasay, Paula Britto, Yan Wang, Li Liu, Sean Brummel, Konstantia Angelidou, Michael Basar, Linda Millar, Kathleen Kaiser, John Gaeddert, Linda Marillo, Andrea Ciaranello, Kenneth Freedberg, Linda Barlow-Mosha, Mary Patricia Toye, Mark Mirochnick, Debika Bhattacharya, Amy Jennings, Adam Manzella, Amanda Zadzilka, William B Kabat, Amy James Loftis, Benjamin Chi, Marc Lallemant, Taha E Taha, Dhayendre Moodley, Karin Nielsen, Arlene Bardeguez, Anna Coutsoudis, Amita Gupta, Risa Hoffman, Elizabeth McFarland, Lynda Stranix-Chibanda, Gerhard B Theron, Lindiwe Msweli, Anne Coletti, Kathleen George, Megan Valentine, Marisol Martinez, James F Rooney, Oxana Ivanova, Danielle Poulin Porter, Wendy Snowden, Helen Watson, Harry Moultrie, Ashraf Coovadia, Renate Strehlau, Gerhard B Theron, Mark Cotton, Magdel Rossouw, Raziya Bobat, Motshidi Sebitloane, Dhayendre Moodley, Avy Violari, Portia Kamthunzi, Mina Hosseinipour, Newton Kumwenda, Mac Mallewa, Pendo Mlay, Anne Buchanan, Namwinga Chintu, Mwangelwa Mubiana-Mbewe, Maxensia Owor, Jim Aizire, Tsungai Chipato, Ramesh Bhosale, Sandhya Khadse

Affiliations

¹ Department of Global Health, University of Washington, Seattle, Washington, USA.
² Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.
³ Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
⁴ Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
⁵ Department of Pediatrics, University of Washington, Seattle, Washington, USA.
⁶ Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.

Abstract

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 >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.

Keywords: EFV; HIV; TLE; pretreatment drug resistance; virologic failure.

Abstract

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