CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

1.42; 95% CI: 0.78 – 2.58). Neither LLV50-199 nor LLV200-499 was associated with occurrence of any serious NAE (aHR: 0.81; 95% CI: 0.37 – 1.75 and aHR: 0.83; 95% CI: 0.34 – 2.07, respectively) Conclusion: In this Spanish cohort, LLV200–499 was strongly associated with AIDS event/death and virological failure, but not with any serious NAE. Therefore, vigorous treatment should be implemented in patients with more than 200 copies 518 VL SUPPRESSION AT ULTRASENSITIVE LEVELS IS ASSOCIATED WITH INSTI-INITIATION ART Sidonie Lambert 1 , Anders Boyd 2 , Djeneba Bocar Fofana 3 , Nadia Valin 3 , Jean-Luc Meynard 3 , Rachid Agher 4 , Vincent Calvez 1 , Christine Katlama 1 , Pierre- Marie Girard 1 , Anne-Geneviève Marcelin 1 , Laurence Morand-Joubert 1 1 Pierre and Marie Curie University, Paris, France, 2 INSERM, Paris, France, 3 Saint- Antoine Hospital, Paris, France, 4 Pitié-Salpêtrière Hospital, Paris, France Background: Some HIV-infected patients on antiretroviral therapy (ART) present ultrasensitive HIV RNA viral loads (US-VL) below detection levels of current VL assays. Little is known regarding the determinants of ultrasensitive detection and its relation to virological failure (VF) in patients undergoing current ART regimens, such as integrase strand transfer inhibitors (INSTI). Methods: HIV-infected, ART-naïve patients from two French university hospitals were included if they had HIV RNA >200 copies/ml at ART- initiation, achieved <50 copies/mL during ART, and had ≥2 follow-up time points. Patients were followed while on continuous ART. Plasma HIV-1 RNA quantification was performed using COBAS TaqMan Roche. US-VL was considered below 1 copy/mL when no signal was detected. Determinants for incidence of US-VL<1 copy/mL were evaluated using mixed-effect Poisson regression and VF (HIV RNA >200 copies/mL once or >50 copies/mL twice) using conditional risk-set Cox proportional hazards models. Results: Between 2009 and 2013, 716 patients initiated ART containing 2 nucleos(-t)ide reverse transcriptase inhibitors (NRTI) plus either a non-NRTI (NNRTI, 29.5%), protease inhibitor (PI, 58.4%) or INSTI (12.2%). Patients were followed for a median 3.4 years (IQR=2.3-4.5), while first-line therapy lasted a median 2.7 (IQR=1.3-5.1) years. US-VL <1 copy/mL was achieved in 674 (94.3%) patients, while suppression at this level was either transient or lasted a median 1.2 years (IQR=0.7-2.0) at most. In multivariable analysis, US-VL<1 copy/ mL over time was associated with decreased age (p<0.001), female gender (p=0.03), lower baseline VL (p<0.001), baseline CD4+>500 versus <350/ mm 3 (p<0.001), and ART containing an INSTI versus NNRTI (p=0.03) or versus PI (p=0.02). VF was observed in 132 (18%) patients during follow-up and was associated with higher baseline VL (p=0.02), and HIV RNA tests/year (p=0.001) after adjustment. In post-hoc analysis, cumulative duration under <1 copy/mL was significantly and inversely associated with VF in the multivariable model (aHR/year of suppression=0.40, 95%CI=0.26-0.62, p<0.001). Conclusion: VL suppression at ultrasensitive levels is associated with the use of INSTI-class ART along with common determinants of undetectable HIV RNA at conventional thresholds. Longer periods at ultrasensitive detection appear to protect against VF. 519 STIMULANT USERS RECEIVING ART DISPLAY INCREASING RATES OF HIV SUPPRESSION AdamW. Carrico 1 , Elise D. Riley 2 , Torsten B. Neilands 2 , Samantha E. Dilworth 2 , Jeffrey N. Martin 2 , Steven G. Deeks 2 , Peter W. Hunt 2 1 University of Miami, Miami, FL, USA, 2 University of California San Francisco, San Francisco, CA, USA Background: HIV-positive persons who use stimulants (i.e., methamphetamine, powder cocaine, and crack-cocaine) experience difficulties navigating the HIV care continuum that undermine the clinical and public health benefits of anti-retroviral therapy (ART). However, stimulant users may be having more success with contemporary ART regimens that are less burdensome and more forgiving of non-adherence. Methods: Study of the Consequences of the Protease Inhibitor Era (SCOPE) is a prospective, clinical cohort following HIV-positive persons on ART with assessments every six months. The exposure was the cumulative, time- varying proportion of assessments with any self-reported use of stimulants. HIV suppression (i.e., viral load less than 200 copies/mL), measured at SCOPE assessments or extracted from the clinical record at San Francisco General Hospital, was the time-varying outcome. We utilized multilevel modeling to

examine whether the odds of HIV suppression among those receiving ART changed over time as a function of stimulant use. Results: From 2000-2016, 1,637 HIV-positive participants on ART (57% Caucasian; 78%men who have sex with men) with a median CD4+ T-cell count of 475 cells/mm 3 at enrollment contributed 17,610 person-visits over an average of 21.2 follow-up assessments. Approximately 42% of participants reported any stimulant use over follow-up. We observed a significant interaction of cumulative, time-varying stimulant use by time (Unstandardized Beta = -0.32; 95% CI = -0.50 – -0.13; p = 0.001) such that stimulant users were slower to achieve the 90% target for HIV suppression (see Figure). Time was significantly and positively associated with greater odds of HIV suppression across all levels of stimulant use: 0% cumulative stimulant use (Odds Ratio [OR] = 1.62 95% CI=1.44 – 1.83); 50% cumulative stimulant use (OR = 1.39; 95% CI=1.25 – 1.54); and 100% cumulative stimulant use (OR=1.18; 95% CI = 1.01 – 1.39). Conclusion: Despite the fact that they achieved HIV suppression at slower rates compared to non-users, stimulant users benefit substantially from ART. Novel approaches are needed to optimize the clinical and public health benefits of ART with HIV-positive stimulant users.

Poster Abstracts

520 FUNCTION OF CD4 RECOVERY AND DECREASING IMMUNE ACTIVATION OF A CHINESE HERB: TWHF Wei Lu , Yuchao Liu, Yang Han, Zhifeng Qin, Xiaojing Song, Taisheng Li Peking Union Medical College Hospital, Beijing, China Background: Chronically enhanced T-cell activation is believed to cause poor recovery in CD4+ T cells in HIV immune non-responders (INRs) after successful antiretroviral therapy (ART). Extracts of Tripterygiumwilfordii Hook F (TwHF, known as “lei gong teng”) have been used as an anti-inflammatory agent to treat rheumatoid arthritis, lupus and nephritic syndrome in China for decades. Our previous pilot study demonstrated that use of TwHF was associated with a reduction in T-cell activation and improved CD4 recovery. Methods: In a multi-centered, double-blinded clinical trial, we enrolled 115 HIV individuals with suboptimal CD4+ T cell recovery (<350/ul) on cART for over 24 months with suppressed viral load (<40 copies/ml) for over 18 months. They were randomly assigned to TwHF group (10mg, tid, n=58) and placebo group (n=57) for 24 weeks with continuous ART. The placebo group was uncovered at week 24 and continued to take TwHF until 48 weeks. T-cell subsets with activation markers and inflammation cytokines were evaluated at baseline, week 12, 24 and 48. Results: Totally 107 patients finished 48 weeks’ follow-up with good tolerance and safety profile. There was significant difference in the mean increase of total and memory CD4+ T cell counts and CD4/CD8 ratio in the TwHF group at week 12, 24 and 48 weeks compared to baseline value. There was no change in CD4+ T cell count in the placebo group during the first 24 weeks, but a significant increase of CD4+ T cell count was seen after transferring the placebo group to TwHF regimen. Interestingly, we demonstrated a significant decrease in IP-10, MCP-1, IFN-α and IFN-γ at week 24 compared to baseline between two groups. There was no similar significant difference seen in sCD14, IL-6, TNF-a, CD38, HLA-DR in either groups.

CROI 2018 189