CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: Grade 2-4, drug-related AEs through Week 12 significantly increased the risk of ART failure at Week 48 by Snapshot (OR 2.68 [95%CI 1.75, 4.11]), and at Weeks 96 and 144; the relationship with any-grade, drug-related AEs through Week 12 was not significant. At Week 48, Snapshot efficacy was 87.9%with ABC-3TC-DTG and 80.1%with TDF-FTC-EFV (Table). ‘Snapshot-Plus’ response rates were substantially lower (76.6% and 62.8%, respectively). DTG minus EFV group differences were significantly greater with ‘Snapshot-Plus’ at each time point (13.8% vs. 7.3% at Week 48; McNemar’s P<0.001), including in the stratumwith baseline viral load <100,000 cp/mL (15.0% vs. 7.7% at Week 48; P<0.001). Conclusion: In this trial, grade 2-4, AE-free ART efficacy was lower than estimated by the standard Snapshot algorithm. The ‘Snapshot-Plus’ algorithmmay be a more clinically relevant measure of ART efficacy, and may better distinguish regimens when used in patients with viral load <100,000 cp/mL. The algorithms should be compared using data from other trials.

Poster and Themed Discussion Abstracts

445 CELLULAR HIV-1 DNA LEVELS AFTER 96 WEEKS OF SWITCH TO ATV/R +3TC IN THE ATLAS-M TRIAL Francesca Lombardi 1 , Simone Belmonti 1 , Eugenia Quiros-Roldan 2 , Alessandra Latini 3 , Chiara Picarelli 1 , Arianna Emiliozzi 1 , Massimiliano Fabbiani 4 , Roberto Cauda 1 , Andrea De Luca 5 , for the AtLaS-M Study Group 1 Catholic Univ of Sacred Heart, Rome, Italy, 2 Spedali Civili di Brescia, Brescia, Italy, 3 IFO S. Gallicano Inst (IRCCS), Rome, Italy, 4 Univ of Milan, Milan, Italy, 5 Siena Univ Hosp, Siena, Italy Background: The AtLaS-M randomized trial showed that in virologically suppressed patients (pts) on atazanavir/ritonavir (ATV/r) with 2 NRTIs, switching to a dual therapy (DT) with ATV/r plus lamivudine (3TC) had superior efficacy as compared to continuing the previous triple therapy (TT). This sub-study was designed to evaluate the impact at 96 weeks of the DT versus the TT on the HIV-1 cellular reservoir as reflected by the quantification of the blood-associated HIV-1 DNA levels. Methods: Total HIV-1 DNA levels in whole blood were quantified at baseline (BL) and after 96 weeks (W96) by a TaqMan real-time PCR assay targeting the HIV-1 5’ LTR region. Plasma residual viremia (RV) (HIV-1 RNA <50 cps/mL) was categorized as detectable (1-49 cps/mL) or undetectable (<1 cp/mL). Logistic regression and Cox proportional hazard models were used to predict the effects of BL HIV-1 DNA levels on risk of RV at W96 and viral rebound (VR)(HIV-1 RNA ≥50 cps/mL during 96 weeks), respectively. Results: A representative subset of 140 of 266 randomized pts was analyzed: 86.4%males, mean age 43.2 yrs and mean CD4 count 657 cell/μL. Main BL characteristics did not differ between pts in DT-arm (n=75) and TT-arm (n=65). The mean BL HIV-1 DNA levels (log10 cps/10^6 leukocytes) in DT (2.42, 95% CI 2.32;2.54) vs TT-arm (2.37, 95% CI 2.24;2.51) were comparable (p=0.570). A significant mean decrease in log10 HIV-1 DNA cps/10^6 leukocytes was observed between BL and W96 in both arms: -0.15 (95% CI -0.23;-0.07, p<0.001) in DT vs -0.18 (95% CI -0.27;-0.08, p<0.001) in TT, without significant differences between the two arms (p=0.703). No demographical, clinical and viro-immunological variable was associated with HIV-1 DNA changes by using linear regression analysis. No significant change in RV levels was observed in both arms (McNemar test, p=ns); detectable W96 RV was associated with higher BL HIV-1 DNA levels compared to undetectable RV (OR: 2.47; 95% CI 1.17;5.19, p=0.017). BL HIV-1 DNA levels was not a predictor of time to VR (p=0.128); pts in the DT-arm had a lower risk of VR (aHR vs TT-arm: 0.29; 95 % CI 0.11;0.83, p=0.021). Conclusion: When compared to continuing 3-drug therapy, DT with ATV/r+3TC resulted in similar decline of HIV-1 DNA levels in pts with sustained viral suppression. HIV-1 DNA load predicted residual viremia but not viral rebound in this setting. These findings support the safety of simplification to ATV/r+3TC on the cellular HIV-1 reservoir. 446 DYNAMICS OF VIRAL LOAD AND CYTOKINES WHEN ART IS INITIATED SOON AFTER HIV ACQUISITION Trupti I. Gilada 1 , Javier R. Lama 2 , Rachel A. Bender Ignacio 3 , Ricardo Alfaro 2 , Carmela Ganoza 2 , Angela K. Ulrich 4 , Socorro M. Harb 3 , Rogelio M. Valdez 4 , Robert Coombs 3 , Ann Duerr 4 1 Unison Medicare and Rsr Cntr, Mumbai, India, 2 Asociacion Civil Impacta Salud y Educacion, Lima, Peru, 3 Univ of Washington, Seattle, WA, USA, 4 Fred Hutchinson Cancer Rsr Cntr, Seattle, WA, USA Background: We analyzed dynamics of HIV-1 viral load (VL) in plasma and semen, and pro-inflammatory cytokines in plasma after ART initiation soon after HIV acquisition. We hypothesized that both cytokine levels and HIV-1 VL would decay more quickly when ART was initiated during Fiebig stages I/II (F I/II) as compared to Fiebig stages III/IV/V (F III/ IV/V) and stage VI (F VI). Methods: This study was conducted in a subset of participants (n=57 MSM/transgender women) from the ongoing ¿Sabes? study in Lima, Peru . All participants tested negative for HIV RNA ≤3 months prior to diagnosis; roughly 1/3rd were diagnosed in F I/II. They were randomized to initiate ART immediately after diagnosis (Immediate) or 24 weeks later (Deferred). HIV-1 RNA in plasma and seminal fluid and cytokine levels in plasma were measured at 0, 1, 2, 4, 8, 12 and 24 weeks after HIV diagnosis. Statistical methods included general estimating equations and a nonlinear mixed effects model. Results: As expected, both plasma and seminal VL declined faster in the Immediate arm (n=26, 7 in F I/II, 11 in F III/IV/V, 8 in F VI at ART initiation) than in untreated participants in the Deferred arm (n=31), after controlling for Fiebig stage (p<0.0001). The decay rate was significantly faster in plasma than in semen (p<0.0001) after controlling for baseline

CROI 2017 185