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

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.

Figure 1.

Promoting Maternal and Infant Survival Everywhere (PROMISE) trial randomization schema for efavirenz-based antiretroviral therapy (ART) substudy participants. The timing of all 3 antiretroviral drug randomizations are shown for each “component” of the PROMISE trial. The number of women in each PROMISE randomization group is shown in parentheses. Participants in this substudy cohort (N = 1233) had efavirenz-based ART prescribed (usually as tenofovir + lamivudine [or emtricitabine] + efavirenz) as part of local standard of care at any phase of the PROMISE trial. The impact of pre-efavirenz-based ART HIV drug resistance on ART suppression was assessed in women prescribed efavirenz-based ART at any phase of the PROMISE study. *Single-dose nevirapine was given at labor/delivery with a “tail” of tenofovir disoproxil fumarate /emtricitabine for 6–14 days to reduce the risk of resistance. †Eligible and willing antepartum and late-presenting mothers and their infants were randomized for the duration of breastfeeding; infants were to be followed to 104 weeks of age. Some mothers who were ineligible for the postpartum component were directly randomized to the maternal health component after delivery. ‡Randomization to the maternal health component occurred at breastfeeding cessation or at or after 74 weeks of breastfeeding for women randomized in the postpartum component. Those randomized directly to the maternal health component after delivery were randomized between 6 and 28 days postpartum. Participants randomized in the antepartum component and not randomized in the postpartum component remained in observational follow-up. Abbreviations: 3TC, lamivudine; ART, antiretroviral treatment; ARVs, antiretroviral drugs; EFV, efavirenz; FTC, emtricitabine; LPV/r, ritonavir-boosted lopinavir; MTCT, mother-to-child transmission; NVP, nevirapine; PROMISE, Promoting Maternal and Infant Survival Everywhere; R, randomization; sdNVP, single-dose nevirapine; TDF, tenofovir disoproxil fumarate; ZDV, zidovudine.