CROI 2016 Abstract eBook

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Poster Abstracts

Methods: We randomly selected 100 participants from each arm, stratifying by baseline CD4 and HIV-1 RNA, age, sex, geography, and excluding patients with cardiovascular disease and those who received statins. Plasma levels were assayed at baseline and weeks 12, 24, and 48 in batch. We summarized baseline levels and percent change from baseline, comparing between arms using Wilcoxon Rank Sum, and within arms and overall using Wilcoxon Signed Rank tests. We tested equivalence between arms using the two-one sided test (TOST). We compared arms with multivariable multiple regression (MMR) to account for correlations among biomarkers. We assessed the biomarkers’ ability to differentiate between arms with the machine learning algorithm Random Forest using a ROC curve and variable importance. Results: A total of 194 patients had evaluable samples (TAF, 98; TDF, 96); 19%women, 44% non-white, 25% VL>100,000 c/mL, and 28% smokers. Median baseline characteristics: age 33, CD4 405 cells/μL, and VL 4.7 log10c/mL were similar to the parent study. Baseline levels of biomarkers did not differ by arm. Overall (both arms pooled), biomarkers of systemic inflammation declined after ART initiation, with statistically significant declines from baseline for IL-6, d-dimer, sCD163 and sTNFR-1 by week 24. Lp-PLA2 levels increased slightly from baseline to 48 weeks (p=0.045). There were no differences in percent change from baseline between groups at weeks 12, 24, or 48 (p>0.05), except IL-6 at week 12 (p=0.012). All biomarkers were equivalent between arms by TOST (90% CIs within 80%-125%) except hsCRP (105.3%, 90%CI [80.7%, 137.4]). By MMR (p=0.9970) and Random Forest (ROC AUC=0.49; 95%CI 0.41-0.57; variable importance scores <0.5%), there was no differentiation between arms by any biomarkers. Conclusions: After initiating ART with either E/C/F/TAF or E/C/F/TDF, there were equivalent declines in biomarkers of monocyte activation and systemic inflammation, supporting that TAF provides similar salutary modulation of inflammation as TDF.

718 Similar Inflammatory Marker Levels With LPV/r+3TC Versus LPV/r+2NRTIs at 48Weeks

Darrell H. Tan 1 ; Maria I. Figueroa 2 ; Mari J. Rolon 2 ; Omar G. Sued 2 ; Janet M. Raboud 3 ; Leah Szadkowski 4 ; Rupert Kaul 5 ; MarkW. Hull 6 ; Sharon L.Walmsley 4 ; Pedro Cahn 2 1 St Michael’s Hosp, Toronto, ON, Canada; 2 Fundación Huésped, Buenos Aires, Argentina; 3 Dalla Lana Sch of PH, Toronto, ON, Canada; 4 Univ Hlth Network, Toronto, ON, Canada; 5 Univ of Toronto, Toronto, ON, Canada; 6 BC Cntr for Excellence in HIV/AIDS, Vancouver, BC, Canada Background: GARDEL was a randomized trial demonstrating the virologic non-inferiority of dual-therapy using lopinavir/ritonavir plus lamivudine (LPV/r+3TC) compared to triple therapy using lopinavir/ritonavir plus two investigator-selected nucleoside reverse transcriptase inhibitors (LPV/r+2NRTIs) in treatment-naïve HIV-infected adults. As residual inflammation has been associated with increased morbidity and mortality in HIV-infected patients, we compared levels of key inflammatory biomarkers between study arms over 48 weeks among GARDEL participants from Argentina. Methods: Plasma collected at baseline, week 24 and week 48 visits was stored at -80C for batched analysis of sCD14, MCP-1, TNF, IL-6, D-dimer and hsCRP. Generalized Estimating Equations with an identity/logit link as appropriate were used to model the impact of dual versus triple ART on each biomarker at 48 weeks, controlling for baseline levels. Additional models estimated the change in biomarker levels over 48 weeks after adjustment for age, sex, baseline CD4 count and baseline log10 HIV RNA. Results: Of 192 GARDEL participants enrolled in Argentina, 171 had samples available from both the baseline and at least one follow-up visit and were eligible for inclusion in the analysis. Median (interquartile range) age was 35 (28,44) years, baseline CD4 count 308 (218,413) cells/mm3, baseline HIV RNA was 5.14 (4.67,5.59) log10 copies/mL. Most participants were Hispanic/Latino (76%), men (79%) with clade B (56%) or BF (27%) infection; only 2%were hepatitis C co-infected. Of the 80 (47%) participants receiving triple therapy, 70 (41% of total) used zidovudine/lamivudine, 7 (4%) used tenofovir plus 3TC or FTC and 3 (2%) switched between these backbones. Overall, over 48 weeks, significant changes were seen in sCD14 (+154 ng/mL, 95%CI=32.8,275), MCP-1 (-0.045 log10 pg/mL, 95%CI=-0.0679,-0.022), TNF (-0.235 log10 pg/mL, 95%CI=-0.262,-0.208), and D-dimer (-0.157 log10 ng/mL, 95%CI=-0.208,-0.106), while no change was seen in hsCRP (-0.0242, 95%CI=-0.133,0.0852) and the odds of having undetectable IL-6 was similar (OR=1.46, 95%CI=0.88,2.43). Dual therapy was not associated with significantly different biomarker levels at 48 weeks relative to triple therapy (Table). Conclusions: In addition to having virologic non-inferiority, LPV/r+3TC dual therapy is associated with similar levels of inflammatory markers over 48 weeks compared to LPV/ r+2NRTIs triple therapy in treatment-naïve adults. The increase in sCD14 over time requires further study.

Poster Abstracts

Differences in inflammatory biomarkers at 48 weeks for dual versus triple therapy

Biomarker

Estimate (95% CI) p

CD14s ng/ml 99.1 (-61.7,260) 0.23 Log10(MCP-1 pg/ml) -0.03 (-0.06,0.00) 0.07 Log10(TNF-a pg/ml) 0.02 (-0.01,0.05) 0.16 Undetectable IL-6 a 1.18 (0.65,2.15) 0.59 Log10(D-Dimer ng/ml) 0.00 (-0.07,0.08) 0.92 Log10(CRP ng/ml) 0.08 (-0.06,0.23) 0.26 a   odds ratio of having a detectable value is presented 

719 Frailty Is AssociatedWith NNRTI-Based Initial ART and Modifiable Risks in ACTG 5322 Kristine M. Erlandson 1 ; KunlingWu 2 ; Susan L. Koletar 3 ; Robert Kalayjian 4 ; BabafemiTaiwo 5 ; Frank J. Palella 6 ; KatherinTassiopoulos 2 1 Univ of Colorado, Denver, CO, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 Ohio State Univ, Columbus, OH, USA; 4 MetroHlth Med Cntr, Cleveland, OH, USA; 5 Feinberg Sch of Med, Northwestern Univ, Chicago, IL, USA; 6 Northwestern Univ, Chicago, IL, USA Background: Frailty is described in HIV infection, particularly among persons with greater historical immune suppression. The impact of initial antiretroviral therapy (ART) selection on subsequent frailty has not been well described in the current ART era.

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CROI 2016