Purpose: Integrated HIV-DNA declines significantly (~5-fold) in the first year of antiretroviral therapy (ART) if individuals are treated early (< 6 months from the infection) but does not decline perceptibly if the individuals are treated with ART during chronic infection (Pinzone et al, 2016; Koelsch et al, 2011, 2008; Murray et al, 2012). Herein, we investigated if early treatment results in sustained accelerated decay of intact proviral DNA after many years of ART. Method: We measured integrated HIV-DNA in samples that were collected after 2 and 7 years of ART in an HIV infected individual treated during acute and chronic infection. From the same samples, we amplified near full length HIV-DNA at limiting dilution and performed Illumina sequencing. We then bioinformatically categorized the proviruses as intact, deleted and hypermutated (Pinzone et al, 2019). Results: In contrast to the rapid decline detected in the first year of ART (Pinzone et al, 2016), the integrated HIV-DNA did not decline between 2 and 7 years of ART in the acutely treated subject. However, sequence analysis revealed that the decline of the intact reservoir between years 2 and 7 was ~4-fold in the chronically treated individual and ~2-fold in the acutely infected individual, despite clonal expansion and the apparent stability of the HIV-DNA. Clonal expansion was more important in the acute patient than the chronic one, especially within deleted proviruses (Fig. 1). Conclusion: Final outcome after 10 years of ART may be a more similar intact reservoir size whether an individual is treated acutely or after chronic infection. Nonetheless, our results also suggest that treating early is beneficial because the reservoir declines more rapidly and thus these individuals are exposed to less harmful inflammation (Fig. 2).
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