Perinatal HIV infection treated ≤48 hours of birth (very early ART [VE-ART]) limited HIV reservoirs and provided 27 months of undetectable viremia off ART in the ‘Mississippi baby’. IMPAACT P1115 is an ongoing prospective phase I/II proof-of-concept study of VE-ART of in-utero infected infants. We report on the completed viral load (VL) response and safety follow-up through 52 wks.
Methods: Newborns enrolled into two cohorts (Fig.1). Cohort 1 (N=440) was treated within 48 hrs of life (Step 1) due to high-risk HIV exposure from untreated maternal infection. 34 had confirmed infection and moved to Step 2. Cohort 2 (N=20) received non-Study triple ARVs ≤48 hrs of life, and directly enrolled into Step 2 with confirmed infection before age 10 days. LPV/r was added to the Step 2 regimen at 42 wks postmenstrual age and NVP stopped with specified virologic criteria (Fig.1). VL was frequently monitored (Fig.1). Virologic failure (VF) was defined as VL ≥200 cp/mL at wk 24, and confirmed VL≥ limit of detection (LOD) at later visits. Probabilities (95% CI) of sustained viral suppression (no VF) were estimated by Kaplan-Meier method. Grade 3 and 4 safety events were assessed for relation to Study ART. Median (Q1, Q3) are presented.
54 HIV-infected infants (61% girls) enrolled from 11 countries; 81.5% breast-fed. Median study enrollment age in Cohort 1 was 22 hrs and 8 days in Cohort 2. For Cohorts 1 and 2 median age at ART initiation was 7.3 (1.8, 21.0) and 33 (0.4, 40.1) hrs, and median earliest VL was 4.9 (4.0, 5.3) and 4.1 (3.2, 5.2) log10 cps/mL, measured at a median of 1 (0,1.0) and 6.5 (2.0, 8.0) days of age; loss to follow-up was 3% and 15%. Estimated probability of sustained viral suppression through 52 wks on Step 2 was 50% (32%, 66%) and 67% (37%, 85%) in Cohorts 1 and 2, respectively; 47/52 who started LPV/r met virologic criteria to stop NVP at median age 29.4 (25.0, 37.7) wks. Grade 3 or 4 related events that were reversible occurred through 52 wks in 15 (44%) and 7 (35%) infants from Cohorts 1 and 2, and were mostly hematologic. There was one death in each cohort, neither related to Study ART. Among infants followed through wk 84, 5/8 and 4/5 in Cohorts 1 and 2 are HIV-seronegative.
VE-ART for infants with in-utero HIV-infection results in moderate rates of strict virologic control through 52 wks. More effective VE-ART regimens are needed to achieve high rates of sustained virologic suppression in infants with in-utero HIV infection