CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: Through Week 48, BMS-663068 continues to show similar efficacy to ATV/r in TE pts. Virologic response rates (mITT and observed) and immunologic reconstitution were similar across the BMS-663068 and ATV/r arms through Week 48. All BMS-663068 doses were generally well tolerated with no dose response safety signals reported. These results support the continued development of BMS-663068. 546 Delay in Antiretroviral Therapy Is Not AssociatedWith Increased Virologic Failure Ashita S. Batavia 1 ; Patrice Severe 2 ; Marc Antoine Jean Juste 2 ; Rode Secours 2 ; Daphne C. Bernard 2 ;William J. Pape 2 ; Daniel Fitzgerald 1 1 Weill Cornell Medical College, New York, NY, US; 2 GHESKIO Center, Port-au-Prince, Haiti Background: Viral load is the most important marker of response to antiretroviral therapy (ART). Decreases in viral load following ART initiation are associated with decreases in mortality and HIV disease progression. Early ART initiation provides added mortality advantages, but it has not been clearly demonstrated whether this is related to differences in rates of virologic failure. Methods: 816 HIV-infected treatment-naïve Haitian subjects with CD4 counts between 200-350 cells/mm 3 were randomized to early (within 2 weeks; N=408) versus delayed ART initiation (CD4 count ≤ 200 cells/mm 3 or development of an AIDS-defining condition; N=408) between 8/1/2005 and 7/31/2008. In the early arm, 340 subjects had viral load data available at 2 years. In the delayed arm, 23 subjects died and 30 were lost prior to ART initiation. Of the 355 subjects in the delayed arm that started therapy, 274 had viral load data available at 2 years. A validated 9-item food security questionnaire was administered at ART initiation, and all subjects were then scheduled for follow-up with a study physician at 1, 2, 3, 6, 12, 18 and 24 months; during these visits ART adherence was assessed using 3-day recall. All analyses were performed using stata 13 software (StataCorps, TX). Results: At ART initiation, subjects in the delayed arm (N=355) had more advanced HIV disease (33.7% vs. 19.10%WHO Clinical Stage III/IV; p-value <0.001) and greater food insecurity (74.1% vs. 54.8% scoring 5-9; p-value <0.001). After 2 years on therapy there was no difference in virologic failure (viral load >50 copies/ μ L) between the arms (21.6% early vs. 22.3% delayed). Table 1 shows that in multivariate analysis the predictors of virologic failure were younger age (OR per additional year 0.98; 95%CI: 0.96-0.99, p-value 0.014), annual income less than US$100 (OR 1.56, 95%CI: 1.06-2.31, p-value 0.026), suboptimal adherence (OR 1.81, 95%CI: 1.25-2.63; p-value 0.002) and number of visits attended (OR 0.68, 95%CI: 0.57-0.82, p-value <0.001).

Poster Abstracts

Predictors of Virologic Failure (Viral load > 50 copies/ μ L) at 2 years: Univariate and Multivariate Logistic Regression Conclusions: Delaying ART initiation until CD4 count ≤ 200 cells/mm 3 or development of an AIDS defining condition resulted in significant pre-ART attrition, interim progression of HIV disease and greater food insecurity. Delayed ART initiation was not associated with increased virologic failure. Predictors of virologic failure were related to age, income and adherence to therapy. 547 Effects of Quadruple First-Line ART on Mucosal Immunity Sergio Serrano-Villar 1 ;Talía Sainz 2 ; Surinder Mann 3 ; Zhong-Min Ma 3 ; Christopher Miller 3 ; Netanya S. Utay 4 ; Basile Siewe 5 ;TaeWook-Chun 6 ; PaoloTroia-Cancio 3 ; David Asmuth 3 1 University Hospital Ramón y Cajal, Madrid, Spain; 2 University Hospital Gregorio Marañón, Madrid, Spain; 3 University of California Davis, Sacramento, CA, US; 4 University of Texas, Galveston, TX, US; 5 Rush University Medical Center, Chicago, IL, US; 6 National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, US Background: HIV infection depletes gut mucosa, which leads to bacterial translocation and T-cell dysfunction. Despite effective ART, CD4+ T-cell depletion and HIV replication persist in the gut. We evaluated the impact of quadruple ART on systemic/mucosal immunity and bacterial translocation. Methods: 33 ART-naïve HIV patients (pts) were randomized to efavirenz (EFV), maraviroc (MRV) or MRV + raltegravir (MRV+RAL), each with TDF/FTC. Colon and duodenal biopsies were obtained at baseline (BL) and at 9 months of suppressive ART. Lymphocyte subsets and activation phenotypes (CD38 + /HLA-DR + ) were measured in peripheral blood (PB) at BL, month 3, 6, and 9 and in duodenum, and colon at BL and month 9 by flow cytometry. Plasma IL-6, lipoteichoic acid (LTA), sCD14 and zonulin were measured by ELISA. Immunohistochemistry (IHC) of duodenal biopsies was performed to determine T cells/mm 2 . Linear mixed models were used to evaluate the association of treatment group with changes in continuous variables. Results: 26 HIV pts completed the follow-up: 8 on the EFV arm, 10 on the MRV arm and 8 on the MVC+RAL arm. Median age was 37 years [25-42]. Median BL PB CD4 counts were 322, 440 and 453 cell/mm 3 , respectively (between-group comparisons, P=ns.). All pts achieved complete HIV suppression. Levels of IL-6, sCD14 and LTA, but not zonulin, improved during the study (P=0.059, 0.038, 0.006 and 0.304). The MVC+RAL group showed greater improvements of sCD14 ( Figure 1A , P=0.039) and zonulin (P=0.015) levels. IHC showed that while both CD4 and CD8 T cell density ameliorated in duodenum, the CD4 subset remained far more impaired than

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CROI 2015