Background
Undetectable or low HIV-1 DNA levels have been associated with a greater likelihood of ART-free viral control in adults treated during primary infection. Here we investigate predictors of HIV-1 DNA levels in a cohort of early-treated children and adolescents recruited on characteristics expected to make them good candidates for future remission/cure trials.
Methods
Parents or guardians of children and adolescents with perinatally-acquired HIV starting ART <3 months of age, >7 years prior and with plasma HIV-1 RNA <50 copies/ml on ART were recruited at 8 sites in South Africa, Mozambique, Uganda, Mali and Thailand. Children who had undergone prior planned or unplanned ART interruptions could also enroll if ART had been resumed for >2 years after interruption. HIV-1 DNA was measured in PBMCs using droplet-digital PCR. Associations between DNA levels and preceding factors were investigated with descriptive statistics and chi-square tests.
Results
ART was started at a median of 65 days (IQR 52-85) among 87 participants (49.4% male) enrolled in this study at a median of 13.2 years of age (IQR 9.6-16.7). Overall, the median HIV-1 DNA level was 340 copies/106cells (IQR: 145- 909) and 10.3% were below the threshold of detection (<1 copy/106 cells). Distributions of HIV-1 DNA did not differ between male and female participants; and, within this truncated range of age of ART start, those starting ART <60 days of age had HIV-1 DNA median 240 copies/106 cells (IQR 83-873; 12.8% undetectable) similar to those starting >60 days: median 396 copies/106 cells (IQR 208-943, 8.3% undetectable). Undetectable HIV-1 DNA was more frequent in those who had undergone a past ART interruption (22.7%) than those who had remained on continuous ART (6.3%) p=0.04. Median age of ART interruption was 1.4 years, two-thirds were planned interruptions as part of the CHER study, and the median duration of interruption was 2.4 months. There were no differences in age of ART start or sex distribution between those with and without a history of interruption.
Conclusions
Around 10% of early-treated children and adolescents well-suppressed on ART for more than a decade had HIV-1 DNA levels below the assay’s detection threshold. Having undergone a prior ART interruption was associated with greater likelihood of undetectable HIV-1 DNA. These results provide intriguing support for the concept of “auto-immunization,” where ART interruption is undertaken to bolster HIV immunity toward ART-free viral control.