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.

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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)