Factors associated with unquantifiable total HIV-1 DNA in peripheral blood in persons living with HIV: An observational study

Background Human immunodeficiency virus (HIV) cannot be eradicated even with suppressive antiretroviral therapy because its retro-transcribed genome integrates into the DNA of the host cells, creating a long-term reservoir. Quantification of total HIV DNA in peripheral blood is a biomarker of this reservoir that can predict the progression of infection, treatment response, and HIV-related complications. A deeper understanding of the reservoir may help develop HIV cures. Objective This study aimed to characterize persons living with HIV-1 (PLWH) with unquantifiable total HIV DNA in the blood below the quantification threshold and identify associated factors. Methods We conducted a retrospective observational study. During the study period, all PLWH who had total leukocyte-associated HIV DNA measured by quantitative PCR were included. We isolated the population of participants with unquantifiable HIV DNA levels below the quantification threshold (40 copies/106 leukocytes). Results Out of 1094 patients analysed, 62 had unquantifiable and 1032 quantifiable HIV DNA levels in the blood. We found that patients with unquantifiable HIV DNA had a higher CD4 nadir (p = 0.006) and a lower viral load zenith (p < 0.001). Multivariate analyses found that initiation of treatment in primary infection was the only protective factor against HIV DNA quantifiability, the odds of HIV DNA quantifiability decreased by 82% in patients who were treated within 30 days after infection, after controlling for other factors. Conclusion Our research highlights the importance of an early start of anti-retroviral therapy to limit the size of the HIV reservoir, as receiving treatment during primary infection was seen as the only protective factor against blood-associated HIV DNA quantifiability.