Proviral HIV-1 DNA Below Detection in Early Treated Adolescents After Prior Treatment Interruption

Background: Low and undetectable HIV-1 DNA levels are associated with greater likelihood of ART-free viral control and may help select candidates for analytic treatment interruption (ATI). We investigated predictors of HIV-1 DNA levels in older children and adolescents with perinatally acquired HIV who started ART early in life. Methods: Children >7 years and adolescents on ART and virally suppressed (<50 copies/ml) who started ART <3 months of age were recruited at sites in South Africa, Mozambique, Uganda, Mali and Thailand. Prior viral rebound or ART interruption was allowed. HIV-1 DNA was measured in PBMCs using droplet-digital PCR. Associations between DNA levels and clinical factors were analyzed using descriptive statistics and chi-square tests. Results: Among 89 participants (50.6% female), ART started at a median age of 66 days (IQR 53–87) and current median age was 12.8 years (IQR 9.6–16.7). Median HIV-1 DNA was 355 copies/10 6 cells (IQR: 151–912); 10.1% were undetectable (<1 copy/10 6 cells). Undetectable results were more frequent in those with ART interruption (21.7%) than continuous ART (6.1%), p=0.0485. This was significant only in females (regardless of ART start age) and only in those who started ART <60 days of age (regardless of sex). Conclusions: About 10% of early-treated children and adolescents suppressed on ART had HIV-1 DNA levels below the assay’s detection threshold. Prior ART interruption was associated with a greater likelihood of undetectable HIV-1 DNA. These results provide support for the concept of “auto-immunization,” where ART interruption may, in certain circumstances, enhance HIV immunity and promote ART-free control.