CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

(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. Conclusion: 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.

Oral Abstracts

125 EARLY DETECTION OF HIV REBOUND BY INNATE SENSORS POST ART INTERRUPTION Julie Mitchell 1 , Eugene Kroon 2 , Khunthalee Benjapornpong 2 , Suteeraporn Pinyakorn 1 , Praphan Phanunphak 3 , Sharon R. Lewin 4 , Jintanat Ananworanich 1 , Mark de Souza 2 , Lydie Trautmann 1 , for the Search 019 Study Group 1 Henry M. Jackson Fndn, Silver Spring, MD, USA, 2 SEARCH, The Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand, 3 Henry M. Jackson Fndn, Bethesda, MD, USA, 4 Doherty Inst for Infection and Immunity, Melbourne, Australia Background: The innate immune system rapidly responds to HIV and this response could potentially be used to detect viral rebound prior to viremia following antiretroviral treatment interruption (TI). We investigated the innate subsets in participants who initiated antiretroviral therapy (ART) during acute HIV infection after TI. Methods: Thirteen HIV infected Thais who initiated ART during Fiebig III-IV (Western blot negative/indeterminate) were studied longitudinally during TI as part of a randomized study of vorinostat/hydroxychloroquine/maraviroc plus ART given for 10 weeks (n=8) vs. ART only (n=5). During TI, dendritic cell (DC) and monocyte subsets were analyzed by flow cytometry and DCs were divided into three populations: CD1c+myeloid DCs (MDCs), CD141+MDCs, and CD303+ plasmacytoid DCs (pDCs). Monocyte subsets were defined by expression of CD14 and CD16. HIV RNA in plasma was measured weekly after TI. Results: At the time of TI, all participants were on ART for ≥ 3 years, with CD4 T cells ≥ 400 cells/mm3 and HIV-1 RNA < 50 copies/ml. Viral load (VL) rebound occurred in all subjects following TI at a median (IQR) of 22 days. At TI, the frequencies of CD1c+MDCs, CD141+MDCs and pDCs were 27.1±8.2%, 0.38±0.36% and 10.7±4.9%, respectively. During TI, we observed a consistent increase in the percentage of pDCs at least one week before VL rebound (median increase =1.40-fold, p=0.01) while there were no consistent changes in the percentage of MDC subsets prior to VL rebound. Additionally, increased surface expression of the DC activation markers PD-L1 and CD69 occurred on pDCs prior to VL rebound (median fold increase: PD-L1=1.39, p=0.008; CD69=1.59, p=0.001). No significant difference was observed in the pDC populations between the two study arms. Analysis of monocyte subsets at TI revealed that 89.5±3.5%were classical, 3.34±1.37%were intermediate, and 1.61±1.04%were nonclassical monocytes. Nonclassical monocytes showed a 2.11-fold increase in frequency (p=0.0002) prior to VL rebound during TI. Conclusion: These data suggest that pDCs, which sense ssRNA viruses, and inflammatory non-classical monocytes are sensing virus prior to measurable HIV RNA levels in the blood. This sensing induces their proliferation, activation and/or recirculation, suggesting that pDCs and nonclassical monocytes are innate sensors of viral replication when ART is stopped and may represent biomarkers prior to viral rebound.

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CROI 2017