Long-term therapeutic impact of the timing of ART in patients diagnosed with primary HIV-1 infection

Abstract

Background

We aimed to determine the consequences of delayed HIV-1 infection diagnosis by comparing long-term outcomes depending on the time of combination antiretroviral therapy (cART) initiation in patients diagnosed during primary HIV infection (PHI).

Methods

We selected patients from the ANRS PRIMO cohort, treated for ≥36 months, with sustained HIV-RNA< 50 copies/mL: 77 treated within one month following PHI diagnosis (immediate ART) and 73 treated >12 months after infection (deferred ART). We measured inflammatory biomarkers from PHI through the last visit on cART, and CD4 ⁺ and CD8 ⁺ T-cell activation and plasma ultrasensitive(us) HIV-RNA at the last visit. Inflammation/activation levels were compared with those of uninfected controls. We modelled the dynamics of CD4 ⁺ counts, CD4:CD8 ratios, and HIV-DNA levels on cART using mixed models.

Results

Patients were mostly Caucasian men (79%). The decrease of HIV-DNA levels on cART was more marked in the immediate than deferred-ART group, leading to a sustained long-term mean difference of -0.6 log₁₀copies/10₆PBMCs. Immediate-ART led to improved CD4⁺ T-cell counts and CD4:CD8 ratios over the first four years of cART. At the last visit (median, 82 months of cART), there was no difference between groups in CD4⁺ T-cell counts, CD4:CD8 ratio, usHIV-RNA or inflammation/activation marker levels. Long-term suppressive cART failed to fully normalize inflammation levels or CD8⁺ T-cell activation, which were not associated with immunovirological marker levels.

Conclusion

ART initiated during PHI promotes the long-term reduction of HIV reservoir size. In patients with sustained virologic suppression, long-term inflammation may be driven by non-HIV-related factors.