Background:
Very early initiation of antiretroviral therapy (ART) may limit the establishment of HIV-1 reservoirs in neonates, potentially enabling ART-free remission. We describe 6 children who received very early NVP- and PI-based ART and underwent analytical treatment interruption (ATI) in IMPAACT P1115 to assess for remission.
Methods:
Fifty-four infants with in utero HIV-1 (confirmed by 2 positive nucleic acid tests) initiated ART within 48 hours of birth and received the study regimen (NVP+2NRTIs with LPV/r added ≥42 weeks postmenstrual age) for up to 294 weeks. Eligibility criteria for ATI included sustained virologic suppression with no plasma HIV-1 RNA detected from 48 weeks onwards and no HIV-1 DNA detected in ≥850,000 PBMCs (droplet digital PCR), normal CD4, and negative HIV-1 serostatus (4th generation ELISA). Children meeting all criteria interrupted ART with frequent clinical, virologic, and immunologic monitoring; remission was defined as no confirmed plasma HIV-1 RNA above the limit of detection (LOD) of the assay for ≥48 weeks off ART. ART was resumed upon viral rebound (HIV-1 RNA confirmed ≥LOD). Plasma ARV drug levels were assessed retrospectively to confirm absence of ARV during ATI.
Results:
Six children underwent ATI at median age 5.5 years. Three of 6 achieved study-defined remission, one through 80 weeks of ATI, when viral rebound (299,538 cp/mL) occurred. The other two who achieved remission remain on ATI (>48 and >60 weeks). A fourth child remains on ATI (>44 weeks). Two children had viral rebound 3 and 8 weeks after ATI (Table). Earliest available HIV-1 RNA and DNA values ranged from 96 to >5 million cp/mL and from not detected to 130 cp/106 PBMCs. The child with 80 weeks of remission had no ARVs detected in plasma during ATI (tests pending for others). Two of 3 children with rebound (at 8 and 80 weeks) experienced acute retroviral syndrome (ARS); no other clinical or immunologic events of concern were identified during or following ATI. The children with rebound at 3 weeks (67,606 cp/mL) and 8 weeks (1801 cp/mL) had HIV-1 RNA <LOD 8 weeks and 20 weeks after resuming ART. The child with rebound at 80 weeks had HIV-1 RNA 724 cp/mL 2 weeks after resuming ART.
Conclusions:
ART-free remission for ≥48 weeks was achieved with very early treatment of in utero HIV-1. Very early treatment with durable virologic suppression may enable sustained remission in children; however, the occurrence of ARS warrants careful clinical oversight during ATI.
