IMPAACT P1115 assesses very early antiretroviral therapy (ART) for remission of in utero HIV-1 infection. We report on virologic outcomes of very early ART and the potential for HIV-1 reservoir reduction by age 2 years.
440 high-risk infants (Cohort 1) were enrolled and initiated presumptive nevirapine (NVP)-based ART by age 48 hours; 34 with in utero infection continued ART. An additional 20 infants with in utero infection who had initiated a 3-drug NVP-based regimen by age 48 hours (Cohort 2) were enrolled by age 10 days (Table). Lopinavir/ritonavir was added when age appropriate; NVP was stopped 12 weeks after confirmed HIV-1 plasma viral load (VL) <20 (Roche TQ) or <40 c/mL (Abbot RT). To stay on study, infants had to maintain virologic suppression (VS), defined as VL <200 c/mL at study week 24, <200 c/mL at weeks >24-<48, and no RNA detected at weeks ?48. Cell-associated HIV-1 DNA (CA-DNA) was measured using a CLIA-certified droplet digital (ddPCR) assay with a lower limit of detection of <4.09 c/106 cells. HIV-1 Ab testing began at week 84. Eligibility for evaluation of remission through ART interruption required maintaining VS, negative HIV-1 antibody (Ab) serostatus, and nondetectable CA-DNA. Estimation included Kaplan-Meier based survival probabilities, exact binomial proportion confidence intervals (CI), and univariate Cox proportional hazards regression (hazard ratio; HR).
At week 24, 75% (24/32, 95%CI 57%-89%) in Cohort 1 and 88% (15/17, 64%-99%) in Cohort 2 had VL <200 c/mL. The estimated probability of remaining VS at age 2 years was 33% (17%-49%) in Cohort 1 and 57% (28%-78%) in Cohort 2. In Cohorts 1 and 2, higher earliest CA-DNA load was associated with increased risk of virologic failure (VF) [per log10, HR 1.66 (0.99-2.80) for Cohort 1, 6.80 (1.31-35.20) for Cohort 2]. In Cohort 1, higher earliest VL was associated with increased risk of VF [per log10, 1.64 (1.06-2.53)] and male sex with decreased risk of VF (0.31, 0.11-0.94). In infants with VS through age 2 years, 83% (52%-100%) in Cohort 1 and 100% (59%-100%) in Cohort 2 tested HIV-1 Ab negative; 64% (31%-89%) in Cohort 1 and 71% (29%-96%) in Cohort 2 had nondetectable CA-DNA. The estimated probability of remaining potentially eligible for ART interruption at age 2 years was 33% (21%-46%).
Infants with in utero HIV-1 infection who maintain virologic suppression with very early ART can achieve restricted HIV-1 reservoirs by age 2 years, which may enable ART-free remission.