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HIV CONTROLLERS MAINTAIN VIRAL SUPPRESSION DESPITE WANING T-CELL RESPONSES ON ART
Nikolaus Jilg1, Pilar Garcia-Broncano2, Michael Peluso3, Florencia Pereyra4, Ronald Bosch5, Carla Roberts-Toler5, Cornelius N. Van Dam6, Michael Keefer7, Daniel R. Kuritzkes4, Alan Landay8, Steven G. Deeks3, Xu G. Yu2, Paul E. Sax4, Jonathan Z. Li4
1Massachusetts General Hospital, Boston, MA, USA,2Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA,3University of California San Francisco, San Francisco, CA, USA,4Brigham and Women's Hospital, Boston, MA, USA,5Harvard University, Boston, MA, USA,6University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,7University of Rochester, Rochester, NY, USA,8Rush University, Chicago, IL, USA
Robust HIV-specific T cell responses are a hallmark of HIV controllers (HCs). We assessed the impact of antiretroviral therapy (ART) on HIV-specific T cell responses and the ability of HCs to maintain HIV suppression after discontinuation of ART.
A5308 is a prospective, open-label study of rilpivirine, emtricitabine and tenofovir disoproxil fumarate (RPV/FTC/TDF) in ART-naive HCs with viral loads (VLs) <500 cp/mL for ≥12 months. HIV-specific T cell responses were measured by intracellular cytokine staining assays in response to HIV gag pool stimulation. Outcomes were evaluated by repeated measures GEE models. In addition, viral load outcomes from HCs in the UCSF SCOPE cohort were included if they had been treated with ART with subsequent VL measurements after ART discontinuation.
Thirty-five HCs completed ≥24 weeks of ART in A5308 and were analyzed. Before ART, higher levels of HIV-specific CD4+ and CD8+ T cell responses were associated with undetectable viremia either by the integrase-single copy assay or the Abbott viral load assay. After 24-48 weeks of ART, significant decreases were observed in a broad range of HIV-specific CD4+ and CD8+ T cell responses. These included CD4+ T cells expressing IFN-γ (-0.32 percentage points (%) [95% confidence interval -0.50%, -0.14%], p<0.001), IL2 (-0.19% [-0.37%, -0.02%], p=0.03), TNFα (-0.53% [-1.1%, 0.02%], p=0.06), and CD8+ cells expressing IFN-γ (-0.23% [-0.47%, 0%], p=0.05), TNFα (-0.32% [-0.58%, -0.07%], p=0.01), and CD107 (-0.38% [-0.82%, 0.06%], p=0.09). Furthermore, significant reductions were found in the percentages of polyfunctional HIV-specific CD4+ and CD8+ cells expressing multiple cytokines (CD4+ IFN-γ+ TNFα+ CD107+: -0.08%, p=0.004; CD8+ IFN-γ+ TNFα+ CD107+: -0.13%, p=0.001). Four HCs from A5308 and 6 HCs from the UCSF SCOPE study discontinued ART after a median [Q1, Q3] of 33 [25, 65] weeks of treatment. Two of the HCs had detectable VLs immediately preceding ART initiation. In the first 24 weeks after ART discontinuation, only 1 of the 10 HCs had a detectable VL (107 HIV-1 RNA copies/mL). This participant also had the highest pre-ART VL (53 HIV-1 RNA copies/mL).
ART significantly reduces both HIV-specific CD4+ and CD8+ T cell responses in HIV controllers. ART did not adversely affect controller status as HIV controllers maintained a low viral load after ART discontinuation.