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THE CHAMP COHORT: POST-TREATMENT CONTROLLERS IDENTIFIED FROM 9 CLINICAL STUDIES
Golnaz Namazi1, Jesse Fajnzylber1, Evgenia Aga2, Ronald Bosch2, Edward P. Acosta3, Jeffrey Jacobson4, Paul Volberding5, Daniel Skiest6, Ronald T. Mitsuyasu7, Robert T. Schooley8, Ann Collier9, Jean-Pierre Routy10, Bruce D. Walker11, Jonathan Z. Li1
1Brigham and Women's Hospital, Boston, MA, USA,2Harvard University, Cambridge, MA, USA,3University of Alabama at Birmingham, Birmingham, AL, USA,4Temple University, Philadelphia, PA, USA,5University of California San Francisco, San Francisco, CA, USA,6Tufts University, Boston, MA, USA,7University of California Los Angeles, Los Angeles, CA, USA,8University of California San Diego, La Jolla, CA, USA,9University of Washington, Seattle, WA, USA,10McGill University, Montreal, QC, Canada,11Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
HIV post-treatment controllers (PTCs) are rare individuals who exhibit sustained HIV remission after treatment interruption (TI). A concerted international effort is needed to identify PTCs given their scarcity at any given research center or clinical trial. We describe PTCs identified from 9 clinical trials and cohorts as part of the Control of HIV after Antiretroviral Medication Pause (CHAMP) cohort. Understanding the incidence of PTC and their post-TI viral dynamics may provide mechanistic insights and has implications for the design of trials aimed at achieving HIV remission.
PTCs were identified from the AIDS Clinical Trials Group (ACTG) studies, the Montreal Primary HIV Infection cohort, the Seattle Primary Infection Program, and the Ragon HIV Controllers cohort. PTCs were defined as individuals who underwent TI and maintained VLs ≤400 copies/mL at ≥2/3 of the time points for at least 24 weeks. Viral load and CD4+ dynamics were compared between PTCs and post-treatment non-controllers (NCs) from ACTG TI trials who received no immunologic intervention and exhibited loss of viral control post-TI.
A total of 58 PTCs were identified. PTCs were more commonly identified in those treated during early infection compared to those treated during chronic infection (11.6% vs. 4.4%, Fishers exact P=0.006). The median duration of documented viral control for the PTCs was 96 weeks. For participants treated during early infection, there was no significant difference between the highest reported pre-ART VL for the PTCs vs. NCs (median 4.6 vs. 4.7 log10 copies/mL). Over 24 weeks of TI, CD4+ counts were generally preserved in PTCs, but declined significantly in NCs (median +4 vs. -200 CD4+ cells/mm3, P<0.001). A VL ≥1000 copies/mL within the first 24 weeks was commonly seen in the PTCs: 24% of PTCs had a peak post-TI VL of 1000-9,999 copies/mL and 10% of PTCs had a peak VL ≥10,000 copies/mL. In those with post-TI VL peak ≥1000 copies, the median VL decline was 1.0 log10 over the subsequent 2 weeks (range 7-15 days).
PTCs were more frequently identified in those treated during early HIV infection and post-treatment control was associated with preserved CD4+ counts over the first 24 weeks. TI trials that restart ART at the 1,000 copy/mL VL threshold will miss 1/3 of PTCs, while trials that use a 10,000 copy/mL threshold will miss 10% of PTCs. Even in PTCs with peak post-TI VLs ≥1000 copies/mL, viral control was achieved relatively rapidly.