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.