Abstract Body

Background: During the earliest weeks of primary HIV infection (PHI), HIV establishes a reservoir mainly in CD4+ T cell subsets. Combined antiretroviral therapy (cART) initiation during PHI yielded better immune restoration and larger decrease in cell-associated HIV-DNA than initiation during the chronic phase. In macaques, the reduction of SIV-DNA reservoir under cART was greater when initiated between 7 and 10 days than between 10 and 42 days after infection. Our objective was to model the short- and long-term decay of the cell-associated HIV-DNA blood reservoir in patients initiating cART during PHI and to assess the impact of the earliness of cART initiation on HIV-DNA level decay.

Methods: We included patients enrolled during primary HIV-1 infection in the multicenter ANRS PRIMO cohort, treated within the month following enrollment and achieving sustained virological response (HIV-RNA <50 cp/mL) as from Month 6. The decay of cell-associated HIV-DNA over time while on successful cART was modeled with a 3-slope linear mixed-effects model.

Results: 327 patients were included, accounting for 1,305 HIV-DNA quantifications. Median time between infection and cART initiation was 41 days (IQR: 33-54), and median follow-up under uninterrupted cART was 2.3 years (range: 0.4-16.6). The impact of the earliness of cART initiation was statistically significant on the first slope (p<0.0001): the earlier cART was initiated after HIV infection, the faster the HIV-DNA level decreased during the first 8 months of cART: -0.171, -0.131, and –0.068 log10 copies/106 PBMC /month when cART was initiated 15 days, 1 month, and 3 months after infection, respectively. The HIV-DNA level continued to decrease significantly under cART after Month 8 but with a lower steepness, and the second and third slopes were similar regardless of cART initiation earliness. The predicted mean HIV-DNA level achieved after 5 years of uninterrupted successful cART was 1.62 log10 copies/106 PBMC when cART was initiated 15 days after infection, and 2.24 log10 copies/106 PBMC when cART was initiated 3 months after infection (p=0.0006). Similar impact of cART earliness on HIV-DNA decrease was found when using the number of antibodies on western blot assay performed at cART initiation as a measure of precocity.

Conclusions: This study provides strong arguments in favor of cART initiation at the earliest possible time point after HIV infection. It also adds further weight for promoting early HIV diagnosis.

Slopes of decay of HIV-DNA under uninterrupted cART with successful virological response (<50 copies/ml from 6 months) predicted by a mixed-effects model, according to cART initiation earliness from HIV infection: the ANRS PRIMO cohort (327 patients, 1,305 measurements)