by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

July 2, 2024

Featured Literature:

Bishop MD, Korutaro V, Boyce CL, et al.  Characterizing HIV drug resistance in cases of vertical transmission in the VESTED randomized antiretroviral treatment trial.  JAIDS.  2024 August 1; 96(4): 385-392.    

This study describes drug resistance among infants whose mothers were enrolled in VESTED, an international open-label trial.  ART naïve adults 14-28 weeks gestation (participants were allowed to have received ≤ 14 days of ART to avoid delays in therapy initiation) were randomized to DTG + FTC/TDF, DTG + FTC/TAF, or EFV/TDF/FTC and followed through 50 weeks postpartum.  Overall, participants were randomized to study ART at a median 21.9 wks GA and 78% breastfed.  Virologic failure was detected in 42, and transmission was detected in 4 (out of a total 617 liveborn infants with complete follow-up).  Case A involved likely in utero infection from pre-treatment viremia, as virologic suppression was achieved and maintained through delivery after study ART initiation (both baseline maternal and infant GRT indicated wild-type virus).  Case B involved likely peripartum transmission due to ongoing viremia throughout pregnancy; further, the evolution of NNRTI mutations [based on results of serial infant testing over the first 2 weeks of life] suggested resistance selected by infant NVP prophylaxis.  Case C involved likely transmission during breastfeeding with new-onset postpartum viremia; although this infant also received NVP prophylaxis, pre-study EFV use (7 days) with emergent K103N in maternal GRT, and K103N detected among 25/25 infant templates sequenced at initial diagnosis suggests transmission of drug resistant virus.  Case D involved persistent viremia on EFV-based therapy, including during breastfeeding (range 59-323 copies/mL), possibly leading to late postnatal transmission.  Authors note NRTI and NNRTI DRM identification in infant samples may be related to subinhibitory concentrations of maternal ARVs in breastmilk selecting for resistance.

Author’s Commentary:

Early initiation of potent, well-tolerated ART leading to durable virologic suppression during pregnancy and postpartum greatly reduces likelihood of perinatal/postnatal transmission.  With changing guidelines for infant feeding particularly in resource rich settings, and a wide range of current infant ARV management and maternal monitoring practices, detailed analyses such as this indeed illustrate “gaps in the identification and treatment of HIV” in women who are or may become pregnant.  This study also helps shed light on the complex issue of perinatal transmission of drug resistant virus.  Although first-generation NNRTIs are no longer considered first-line therapy and relatively few pregnant people are currently receiving these combinations, nevirapine is still used commonly as infant prophylaxis.  This, plus ongoing limited data on ARV concentrations in breastmilk, underscore the need for potent prophylaxis options for infants exposed to maternal viremia with HIV drug resistance.

View archived Clinical Research Update entries here.