Brief Report: Characterizing HIV Drug Resistance in Cases of Vertical Transmission in the VESTED Randomized Antiretroviral Treatment Trial

Abstract

Introduction: VESTED (Virologic Efficacy and Safety of ART combinations with tenofovir alafenamide fumarate (TAF)/tenofovir disoproxil fumarate (TDF), efavirenz, and dolutegravir)(NCT03048422) compared the safety and efficacy of 3 antiretroviral treatment (ART) regimens in pregnant and postpartum women: dolutegravir + emtricitabine/TAF, dolutegravir + emtricitabine/TDF, and efavirenz/emtricitabine/TDF. Vertical HIV transmission (VT) occurred in 4 of 617 live-born infants (0.60%), who were evaluated for HIV drug resistance (HIVDR) and other risk factors. Setting: In 2018–2020, pregnant women (weeks 14–28) living with HIV underwent ≤14 days of ART were enrolled at 22 international sites and followed with their infants through 50 weeks postpartum. Methods: HIV sequences derived by single-genome amplification from longitudinally collected specimens were assessed from VT cases for HIVDR in protease, reverse transcriptase, integrase, and the nef 3′polypurine tract (3′PPT). Results: The 4 case mothers were prescribed efavirenz-based ART for 1–7 days before randomization to study ART. Their infants received postnatal nevirapine ± zidovudine prophylaxis and were breastfed. A total of 833 single-genome amplification sequences were derived. The “major” (Stanford HIVDR Score ≥60) non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation (K103N) was detected persistently in 1 viremic mother and likely contributed to VT of HIVDR. Major NNRTI HIVDR mutations were detected in all 3 surviving infants. Neither integrase nor high frequencies of 3′PPT mutations conferring dolutegravir HIVDR were detected. The timing of HIV infant diagnosis, plasma HIV RNA levels, and HIVDR suggests 1 in utero, 1 peripartum, 1 early, and 1 late breastfeeding transmission. Conclusions: VT was rare. New-onset NNRTI HIVDR in case mothers was likely from efavirenz ART or dolutegravir ART prescribed before study, and in 1 case, it seemed transmitted to the infant despite nevirapine prophylaxis. NCBI GenBank Accession Numbers: OQ911992-OQ912874.