CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

403 IMPACT OF ATI ON HIV RESERVOIRS AND IMMUNE PARAMETERS IN EARLY TREATED INDIVIDUALS Erin Huiting , Jana Blazkova, Jesse Justement, Victoria Shi, Kathleen Gittens, Susan Moir, Michael Sneller, Anthony S. Fauci, Tae-Wook Chun NIAID, Bethesda, MD, USA Background: Eradication of HIV from an infected individual is not feasible with current antiretroviral therapy (ART) and the vast majority of individuals experience plasma viral rebound upon cessation of therapy. Given the current requirement for life-long therapy in individuals whose virus has been successfully suppressed with ART, novel therapeutic strategies aimed at achieving drug-free HIV remission are being explored in infected individuals who began ART during the acute/early phase of infection. Such strategies would require analytical treatment interruption (ATI) for proof of concept. Thus, it is of considerable interest to investigate the impact of ATI on the HIV reservoir and immune parameters in such infected individuals. Methods: Longitudinal immunologic and virologic analyses were conducted on specimens obtained from 22 individuals treated early in the course of infection who previously participated in a therapeutic vaccine trial. The dynamics of HIV reservoirs and immunologic parameters were examined in the study subjects prior to ATI, during ATI, and following reinitiation of ART. Results: The median duration of the ATI phase was 124 days (range 56-242). At baseline, the frequency of CD4+ T cells carrying replication-competent HIV positively correlated with that of cells carrying HIV DNA and inducible cell-free virions. Following discontinuation of ART, all study subjects experienced plasma viral rebound and significant increases in the frequency of CD4+ T cells carrying HIV proviral DNA and cell-associated RNA, as well as the level of immune activation in the CD8+ T cell compartment (CD38+DR+). In addition, the levels of CD4+ T, B, and natural killer cells decreased following plasma viral rebound during the ATI phase. However, the size of the HIV reservoirs, including replication-competent virus and inducible cell-free virions, and all immune parameters returned to baseline (pre-ATI) levels after ART was resumed and maintained for a median of 58 months (range 30-89). Conclusion: Our findings demonstrate that short-term ATI does not cause permanent expansion of HIV reservoirs nor irreparable damages to the immune system in individuals who initiated ART during the acute/early phase of infection. Therefore, our data support the use of ATI as a crucial component of clinical trials designed to examine the efficacy of therapeutic interventions as a substitute for ART in infected individuals who initiated ART during the early phase of infection. 404 DETECTION OF CELL-ASSOCIATED HIV-1 NUCLEIC ACID IN BLOOD AFTER EARLY ART Linda Jagodzinski 1 , Mark M. Manak 2 , Holly R. Hack 2 , Jennifer Malia 1 , Nittaya Phanuphak 3 , Mark de Souza 3 , Eugène Kroon 3 , Donn J. Colby 3 , Nitiya Chomchey 3 , Merlin L. Robb 4 , Nelson L. Michael 1 , Jintanat Ananworanich 4 , Sheila A. Peel 1 , for the RV254/SEARCH010 study group 1 Walter Reed Army Institute of Research, Silver Spring, MD, USA, 2 Henry M Jackson Foundation, Silver Spring, MD, USA, 3 SEARCH, Bangkok, Thailand, 4 Henry M Jackson Foundation, Bethesda, MD, USA Background: Initiation of HIV-1 antiretroviral drug therapy (ART) during acute infection can delay HIV seroconversion and reduce the HIV viral reservoir. The Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test v2.0 (CAP/CTM), capable of detecting both HIV RNA and DNA, was used to measure the levels of Cell Associated HIV-1 (CAH) nucleic acid in Peripheral Blood Mononuclear Cells (PBMCs) prior to and post initiation of ART during acute HIV infection. Methods: PBMCs from 37 participants enrolled in the HIV early treatment study (RV254/SEARCH010, Bangkok, Thailand) were selected based upon Fiebig Stage (FI-VI) at time of ART initiation: FI (N=9), FII (N=6), FIII (N=7), FIV (N=7), FV (N=5), and FVI (N=3). Cell lysates of 1 million PBMCs collected at week 0 and weeks 1/2, 8 and 60 post ART initiation were tested in triplicate by CAP/CTM. Results: Plasma HIV-1 RNA levels prior to ART initiation ranged from 2.43-5.16 and 4.17-6.9 log c/ml for individuals in F1 and FII-FVI, respectively. Initiation of ART resulted in a rapid loss of plasma HIV-1 RNA and suppression of HIV virus in all individuals by week 8. CAH levels averaged 1.44 log c/million PBMCs in FI untreated individuals, with 5/9 (55.6%) at or below Limit of Quantitation (LOQ: 1.42 log c/million PBMCs) for the assay. The average CAH log c/million PBMCs for untreated FII was 4.08 and 3.61 for untreated FIII-FVI. CAH at week 8 for F1 treated individuals was near or at the LOQ (3/9), and 6/9 (67%) were not detected. At week 60, 8/9 (88.9%) FI treated individuals were undetectable. At

week 8, 4/13 (30.8%) FII/FIII treated individuals were near or below LOQ; and 6/13 (46.2%) by week 60. Only 2/13 (15.4%) were undetected. For individuals treated at FIV-FVI, 4/15 (26.7%) were near or at the LOQ by week 60 with CAH levels in 10/15 individuals ranging from 1.44-3.01 log c/million PBMCs. Conclusion: HIV nucleic acid persists in PBMCs of infected individuals under therapy and can be readily monitored by the CAP/CTM assay in the absence of detectable plasma HIV-1 RNA. Only FI treated individuals had consistently undetectable CAH by week 8. ART resulted in a logarithmic decline in CAH with an initial rapid loss followed by a more gradual decrease. The residual HIV reservoir at 60 weeks increased when treatment was initiated at later Fiebig stages. Testing of PBMCs by the Roche CAP/CTM assay provides a convenient measure of residual HIV reservoir in blood and may be useful for monitoring patients under therapy and in HIV remission studies. 405 ALTRUISM IN END OF LIFE HIV RESEARCH: INSIGHTS FROM LAST GIFT STUDY Karine Dube 1 , Anshula Nathan 1 , Kushagra Mathur 2 , Susanna Concha-Garcia 2 , Hursch Patel 1 , Andy Kaytes 3 , Jeff Taylor 2 , Davey M. Smith 2 , Sara Gianella 2 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 University of California San Diego, La Jolla, CA, USA, 3 University of California San Diego, San Diego, CA, USA Background: End-of-life (EOL) HIV cure-related research provides a novel approach to study HIV reservoirs and promising HIV cure research interventions. The Last Gift is a clinical research study at the University of California San Diego enrolling terminally ill persons living with HIV (PLWH) to contribute towards HIV cure science without personal benefits. As part of a socio-behavioral sub-study we elucidate motivations for participation and experiences while in the study. Methods: The Last Gift study enrolled 7 participants since summer 2017 (n=7 males; aged 45–72 years). All were first-time HIV cure research participants but were not new to clinical research. Along with HIV, they had a terminal illness with a prognosis of <6 months. Ante-mortem procedures involved blood draws, baseline and follow-up interviews. Post-mortem procedures involved a rapid autopsy (<6 hours of death) to characterize the size, distribution and molecular characteristics of HIV reservoirs in various tissues. Results from the socio- behavioral interviews to Last Gift participants and their Next of Kin (NOK) were transcribed verbatim and coded using thematic analysis. Questions included (1) motivation for participation, (2) perceived benefits, (3) understanding of the study goals, (4) meaning of the Last Gift study, (5) post-mortem insights or concerns (NOK only). Results: Deep altruism (but not monetary compensation) was the main motivator to participation. All Last Gift participants and NOK expressed psychosocial benefits and meaningfulness from being part of the Last Gift study. Participants and NOK displayed a sophisticated understanding of the study and its purpose. NOK did not perceive any risks or ethical concerns towards study participation but would like to be included earlier in the process. The post-mortem interviews were emotional and overwhelmingly positive. NOK expressed that the study benefited the grieving process and they did not report any decisional regrets from Last Gift participants. Conclusion: Interviews identified societal and psychological benefits to participation in the Last Gift study. Terminally ill PLWH valued the altruistic benefits and the deep sense of purpose of being an integral part of HIV cure research. Thus, we are encouraged to continue the development of our EOL research model. Results emphasize the importance of incorporating perceptions of family members, as well as socio-behavioral research methodologies to understand the effects of participation on everyone involved. 406 WITHDRAWN / INTENTIONALLY UNASSIGNED 407 EARLY INFLAMMATORY PROFILES IN LONG-TERM VIRALLY SUPPRESSED WOMEN PREDICT COGNITION Raha Dastgheyb 1 , Dionna W. Williams 1 , Yanxun Xu 2 , Kathryn Fitzgerald 1 , Xuzhi Wang 2 , Sheila Keating 3 , Philip J. Norris 3 , Robert C. Kaplan 4 , Pauline M. Maki 5 , Norman J. Haughey 1 , Seble Kassaye 6 , Deborah Gustafson 7 , Victor Valcour 8 , Leah H. Rubin 1

Poster Abstracts

CROI 2019 146

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