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HIV RNA REBOUND POSTINTERRUPTION IN PERSONS SUPPRESSED IN FIEBIG I ACUTE HIV
Donn Colby1, Nicolas Chomont2, Eugene Kroon1, Louise Leyre2, Suteeraporn Pinyakorn3, Nelson L. Michael3, Merlin L. Robb3, Nittaya Phanuphak1, Jintanat Ananworanich3
1SEARCH, The Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand,2Cntr de Rsr du Cntr Hosp de l'Univ de Montréal, Montréal, Canada,3US Military HIV Rsr Prog, Bethesda, MD, USA
Initiation of antiretroviral therapy (ART) during acute HIV infection (AHI) minimizes establishment of a latent HIV reservoir. This could, in turn, delay viral rebound following treatment interruption (TI) and potentially induce a post-treatment controller state. We investigated time to viral load (VL) rebound after ART cessation in participants who initiated ART during AHI.
Eight participants (7 male, 1 female) who initiated ART in Fiebig I (VL+, p24-, IgM-) acute infection and had VL<20 copies/ml on ART for a median of 2.8 (range 2.5-5.5) years before undergoing TI with VL monitoring every 3-7 days. VL, CD4/CD8, HIV DNA and inducible HIV RNA were examined. There was 85% power to reject the null hypothesis of 5% rate of VL < 50 copies/ml at 24 weeks post-TI if the true rate was 30% or greater.
The median (range) age was 29 (22-34) years. HIV subtypes were CRF01_AE (n=6) or CRF01_AE/B (n=2). Median (range) pre-ART values included HIV RNA 4.2 (3.3-4.9) log10copies/ml, HIV DNA 66 (0-490) log10copies/106CD4, and CD4 413 (227-565) cells/mm3. Prior to TI, median (range) CD4 was 561 (425-654) cells/mm3. Total HIV DNA (LOD 5 copies/106CD4) and inducible HIV RNA (LOD 1.4 tat/rev RNA+cells/106CD4) were undetectable for all participants. All participants experienced VL rebound post-TI at a median (range) time of 26 (13-48) days (Figure). VL at first detection was 2.1 (1.4-3.9) and the highest VL was 3.7 (3.3-4.1) log10copies/ml after 4 (1-12) days from first VL detection. CD4 change was -9 (-87 to +39) cells/mm3. There were no symptoms consistent with acute retroviral syndrome, new resistance mutations or treatment failures after ART resumption. Four of 6 participants with non-reactive 4th generation immune assay seroconverted after VL rebound. Pre-TI CD4/CD8 ratio ≤ 1 predicted time to VL rebound (p-value log-rank test 0.004). HIV reservoir markers pre-ART and pre-TI were not predictive.
ART initiated in Fiebig I did not result in a significantly longer time to VL detection post-TI compared to published chronic HIV cohorts infected with other HIV-1 subtypes. Despite achieving extremely small HIV reservoir size, early ART alone will infrequently induce HIV remission and additional strategies to eliminate or control latently infected cells will be required.