CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

675 GREATER ART ADHERENCE IS ASSOCIATED WITH LESS INFLAMMATION IN HIV-SUPPRESSED UGANDANS Jose Castillo-Mancilla 1 , Mary Morrow 2 , Yap Boum 3 , Jessica E. Haberer 4 , Jeffrey N. Martin 5 , David Bangsberg 6 , Samantha MaWhinney 1 , Nicholas Musinguzi 7 , Peter W. Hunt 5 , Mark J. Siedner 4 1 Univ of Colorado Denver, Aurora, CO, USA, 2 Colorado SPH, Aurora, CO, USA, 3 Epicentre, MSF, Mbarara, Uganda, 4 Massachusetts General Hosp, MA, USA, 5 Univ of California San Francisco, San Francisco, CA, USA, 6 MGH-Ragon Inst, Boston, MA, USA, 7 Mbarara Univ of Sci and Tech, Mbarara, Uganda Background: Residual inflammation persists in individuals living with HIV who achieve viral suppression. Because higher levels of inflammation predict cardiovascular events and mortality, there is great interest in identifying interventions to reduce inflammation in this population. We aimed to determine if ART adherence, measured by electronic monitoring, has an inverse relationship with inflammation among individuals who achieve HIV viral suppression. Methods: We enrolled adults living with HIV in Mbarara, Uganda, and measured interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, kynurenine/tryptophan (K/T) ratio, and CD8+ T cell activation (HLA-DR+/CD38+ co-expression) at ART initiation and 6 months later. Adherence was measured with the Medication Event Monitoring System (MEMS) and calculated by averaging daily observed/prescribed device openings per participant over the 6-month period, capping daily adherence at 100%. We limited our analysis to participants who achieved viral suppression (<400 copies/ml) and had biomarker levels at baseline and the 6-month visit. We graphically depicted relationships between average adherence and the log-transformed inflammatory biomarkers at 6 months, and identified a linear relationship between them. We then fit linear regression models to estimate the relationship between adherence and biomarkers of inflammation after 6 months of ART, adjusting for baseline biomarker levels. Results: Median (IQR) age was 35 (30, 40) years, and 196 (70%) of participants were women. Median (IQR) adherence was 88 (84, 98) percent. Most participants (61%) were taking zidovudine/lamivudine/nevirapine, or lamivudine/stavudine/nevirapine (28%). At baseline, median (IQR) CD4+ cell count was 134 (80, 198) cells/mm3 and 151 (54%) had an HIV viral load >100,000 copies/ml. Among those suppressed after 6 months of ART, each 10% increase in average adherence was associated with lower plasma levels of IL-6, D-dimer, K/T ratio and sCD14 (Table). Conclusion: Among HIV-infected patients who achieved viral suppression during early ART in rural Uganda, higher adherence is associated with lower biomarkers of inflammation. ART adherence could have significant biological consequences beyond viral suppression, possibly driven by mitigating viral replication below clinically-available laboratory thresholds. Whether this association persists during chronic suppression, or if optimized ART adherence in virologically-suppressed individuals could reduce inflammation-related morbidity, remains unknown.

Poster and Themed Discussion Abstracts

676 IMMUNOLOGICAL EFFECTS OF SYNBIOTIC SUPPLEMENTATION IN ADVANCED HIV DISEASE Sergio Serrano-Villar 1 , Maria Lagarde 2 , Jose I. Bernardino 3 , Mariano Matarranz 2 , Alfonso Cabello 4 , Judit Villar 5 , Jose Ramón Blanco 6 , Otilia Bisbal 2 , Alberto Díaz de Santiago 7 , Vicente Estrada 8 1 Hosp Univ Ramón y Cajal, Madrid, Spain, 2 Hosp 12 de Octubre, Madrid, Spain, 3 Hosp Univ La Paz–IdiPAZ, Madrid, Spain, 4 Hosp Univ Fndn Jiménez Díaz, Madrid, Spain, 5 Hosp del Mar, Barcelona, Spain, 6 Hosp San Pedro, La Rioja, Spain, 7 Hosp Puerta de Hierro, Madrid, Spain, 8 Hosp Univ Clínico San Carlos, Madrid, Spain Background: Late diagnosed HIV-infected subjects show impaired immunological recovery resulting in a greater risk of clinical progression. Gut bacteria metabolism appears to impact immune recovery in HIV-infected subjects, and while nutritional interventions with prebiotics and probiotics seem to exert immunological effects, the clinical implications in this key population remain unknown. Methods: Pilot multicenter randomized placebo-controlled, double blind clinical trial in which 76 HIV-infected ART-naive subjects with <350 CD4 T cells/mm3 or AIDS were randomized (1:1) to either the synbiotic nutritional supplement PMT25441 or placebo for 48 weeks, each in combination with first-line ART. Primary outcomes were safety and immunological recovery. Secondary outcomes included changes in fecal microbiota structure and plasma inflammatory markers. We herein report an intention-to-treat analysis of the 24-week data on the primary outcome. We used linear mixed models with robust variance estimators and interaction terms to assess whether changes in longitudinal variables over time differed significantly between arms. Results: 64 patients completed the follow-up, mean age 37±12 years, 78%MSM, CD4 T cells 225±110/mm3, CD4/CD8 ratio 0.26±0.19, 12% diagnosed with an AIDS-defining condition. All patients initiated triple ART (61%with integrase inhibitors) and 92.2% had HIV RNA <400 copies/ml at week 24. Baseline characteristics were balanced between arms. Overall, PMT25341 was well tolerated despite frequently reported bad taste, and non grade 3-4 adverse effects attributable to the intervention were identified. We did not detect statistically significant differences in CD4 T cells or CD4/CD8 ratio over the study period. For CD4 T cells, mean difference relative to placebo was -14 cells/mm3 (95%CI -87, 59) at week 4 and -19 (95%CI -103-63) at week 24, and for CD4/CD8 ratio 0.09 (95%CI -0.002, 0.18) at week 4 and 0.05 (95%CI -0.07, 0.17) at week 24. Conclusion: While a positive effect on CD4 T counts has been observed in previous studies evaluating the impact of prebiotics and probiotics in ART-naive subjects, our data suggest that the clinical impact of nutritional strategies aimed at restoring the gut microbiota might be very limited in HIV-infected patients initiating ART at advanced disease. 677 BONE MICROARCHITECTURAL CHANGES AND FRACTURE-RISK PREDICTION IN HIV AND HCV Roger Bedimo 1 , Beverley Adams-Huet 2 , John Poindexter 2 , Irfan Farukhi 3 , Rosinda Castanon 3 , Geri Brown 3 , Diana Turner 3 , Teresa Moore 3 , Pablo Tebas 4 , NaimMaalouf 2 1 VA North Texas Hlth Care Cntr, Dallas, TX, 2 Univ of Texas Southwestern Med Cntr, Dallas, TX, 3 VA North Texas Hlthcare System, Dallas, TX, 4 Univ of Pennsylvania, Philadelphia, PA Background: Both HIV and HCV infections are associated with an increased risk of osteoporotic fractures (OF). HIV/HCV co-infected subjects have a 3-fold increased fracture incidence compared to uninfected individuals, and have a greater risk than HIV or HCV mono-infected. Trabecular bone score (TBS) is a novel practical, non-invasive measurement of bone microarchitecture from dual x-ray absorptiometry (DXA) images. TBS is a proven OF predictor, even after adjusting for BMD, and is now included as an independent risk factor in the FRAX® algorithm for fracture risk prediction. Our goals were: 1) To evaluate if micro-architectural changes underlie the increased fracture risk in HIV/HCV and HCV infection 2) To evaluate the impact of impact of including TBS in FRAX score among HIV and HCV infected patients

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