The build-up of stock of stable integrated proviruses overtime explains the difficulty in reducing HIV-1 DNA levels when treatment is initiated at the chronic stage of the infection

Background: Understanding factors affecting the size and the evolution of the HIV reservoir is essential for the development of curative strategies. This study aimed to assess the impact of antiretroviral therapy (ART) initiated during primary infection (PHI) vs chronic infection (CHI) on the levels and dynamics of integrated HIV-1 DNA, a biomarker of viral persistence.

Methods: Integrated and total HIV-1-DNA were measured in the blood of 92 patients treated during PHI (early group) and 41 during CHI (deferred group), at diagnosis, ART initiation, and 12-24 months on treatment.

Results: On ART, detectable (>1.78 log₁₀ copies/10⁶ PBMCs) integrated HIV-1 DNA levels were significantly lower in the early vs deferred group (2.99 log₁₀vs 3.29 log_10,p = 0.005). The proportion of undetectable integrated HIV-1 DNA tended to be higher in the early group vs deferred group (61 % vs 46 %; p = 0.133).

Conclusion: Treatment initiated at PHI limits the levels of integrated HIV-1 DNA in blood. However, initiating treatment at CHI does not allow reaching such low levels in most patients, probably because the stable proviruses at that stage are present in the less prone to elimination long-lived cells. Thus, early ART could provide an opportunity to preparing for functional cure and eradication strategies.