CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

717 IMPACT OF TREAT-ALL GUIDELINES ON TB INCIDENCE AMONG PLWH IN RIO DE JANEIRO, BRAZIL Lelia H. Chaisson 1 , Valeria Saraceni 2 , Juliana Domenico 2 , Richard D. Moore 3 , Richard E. Chaisson 3 , Jonathan Golub 3 , Betina Durovni 4 1 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 Secretaria Municipal de Saúde do Rio de Janeiro, Rio de Janeiro, Brazil, 3 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 Oswaldo Cruz Foundation - Fiocruz, Rio de Janeiro, Brazil Background: Antiretroviral therapy (ART) substantially lowers tuberculosis (TB) risk, and implementation of universal ART ("treat all") guidelines therefore has the potential to reduce TB burden among people living with HIV (PLWH). We evaluated the impact of treat all guidelines on TB incidence and mortality in Rio de Janeiro, Brazil. Methods: Brazilian guidelines recommended ART for patients with CD4≤500 from 2010-2013 and treatment for all starting in 2014. We included all PLWH entering public sector care in Rio from 2010-2016 with follow-up through 2017, excluding those with prevalent TB. We used national electronic registries to obtain data on CD4s, viral loads, TB diagnoses, ART prescriptions, and deaths; and joined databases using probabilistic linkage. We followed patients from entry into care until TB diagnosis, death, or administrative censoring at 2 years. We calculated incidence rates (IR) per 100 person-years (pys) and the 2-year cumulative hazard (CH) of 1) TB and 2) TB/death prior to and following implementation of treat all guidelines, stratified by baseline CD4 and ART status. Results: 16,552 PLWH entered care from 2010-2016; 5,675 (34%) were female and median age was 34 years (IQR 27-43). Baseline CD4 was ≤500 in 6,902 (42%), >500 in 4,013 (24%), and unknown in 5,637 (34%). Overall, 8,446 (51%) started ART, 248 (1.5%) developed TB, and 893 (5.4%) died within 2 years. IR by entry year are shown (Table). There was a 22% reduced rate of TB (IR ratio 0.78, 95% CI 0.61-0.99) and TB/death (IR ratio 0.78, 95% CI 0.69-0.88) post treat all compared with pre treat all. The 2-year CH of TB and TB/death declined between periods for those with unknown baseline CD4s (TB: 2.2% vs 1.7%, p=0.14; TB/ death: 7.2% vs 5.4%, p=0.01) but did not decline for those with CD4≤500 (TB: 1.8% vs 1.9%, p=0.82; TB/death: 10.8% vs 10.1%, p=0.49) or CD4>500 (TB: 0.6% vs 0.7%, p=0.78; TB/death: 2.4% vs 2.1%, p=0.50). ART was associated with a 66% reduced rate of TB (IR ratio 0.34, 95% CI 0.22-0.52) and TB/death (IR ratio 0.34, 95% CI 0.28-0.42) in the pre treat all period; in the post treat all period, ART was associated with a 17% reduced rate of TB (IR ratio 0.83, 95% CI 0.59-1.17) and a 44% reduced rate of TB/death (IR ratio 0.56, 95% CI 0.47-0.67). Conclusion: Risk of TB and death fell in the treat all era in Rio but remains high. ART coverage must increase, and additional interventions, including TB preventive therapy, should be scaled-up to reduce TB morbidity and mortality.

716 INFLAMMATION AND MITOCHONDRIAL DYSFUNCTION NOT NRTIs DRIVE EVENTS IN ACTG A5241 Carl J. Fichtenbaum 1 , Timothy M. Stone 1 , Gregory S. Gojanovich 2 , Roman Jandarov 1 , Joseph J. Eron 3 , Rajesh T. Gandhi 4 , Karen T. Tashima 5 , Mariana Gerschenson 2 , for the AIDS Clinical Trials Group 1 University of Cincinnati, Cincinnati, OH, USA, 2 University of Hawaii at Manoa, Honolulu, HI, USA, 3 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 4 Massachusetts General Hospital, Boston, MA, USA, 5 Brown University, Providence, RI, USA Background: ACTG A5241 (OPTIONS Study) randomized individuals experiencing treatment failure to omit or add nucleoside reverse transcriptase inhibitors (NRTIs) to a regimen that had a cumulative activity of 2 or more active antiretroviral agents. There were more deaths and clinical events observed in those randomized to add NRTIs. We hypothesized that clinical events were associated with markers of inflammation and mitochondrial dysfunction. Methods: Cohort study of 174 participants enrolled in OPTIONS (N=413) selected randomly and enriched to include those with clinical events (death, AIDS defining opportunistic infections and non-AIDS clinical events). Protein levels relating to inflammation (IL-6, TNFr1, TNFr2, sCD14, CRP, Insulin) or mitochondrial dysfunction (NADH dehydrogenase [C1], FGF21 and GDF15) were measured by Luminex and ELISA, respectively at baseline, weeks 24 and 48 and evaluated for their association with the composite endpoint of clinical events. At baseline sampling, all participants were taking a failing regimen of NRTIs plus protease inhibitors. The statistical analysis included univariate parametric (t- tests) and non-parametric tests (Wilcoxon test) with selected variables analyzed using linear and generalized linear models. Results: 174 participants were evaluated with a median age of 47 years, 40%women; 43% Black, 20% Hispanic/Latino, 36%white. There were 58 participants with clinical events and 116 participants without clinical events of whom 35% vs. 36%were randomized to omit NRTIs, respectively. At baseline, sCD14 (555,263 vs 448,584 pg/mL, P=0.03); CD4 count (148 vs. 209 cells/mm 3 , P=0.03); CD4:CD8 ratio (0.16 vs 0.22, P=0.02) and VACS Index (46 vs. 33, P=0.02) were significantly different in those who subsequently experienced a clinical event. At baseline, there were no significant differences in the two groups NADH dehydrogenase activity, FGF-21, GDF-15, IL-6, TNFr1, TNFr2, insulin or HIV RNA levels. Censoring for those with clinical events before weeks 24 or 48, FGF-21, sCD14, CD4, CD4:CD8 ratio and VACS index were significantly different at weeks 24 and 48 (Table). Analyses were similar when adjusted for randomization to omit or add NRTIs. Only sCD14 remained significant on multivariate analyses at baseline, week 24 or week 48 (Odds ratio, 1.0). Conclusion: Severity of illness, biomarkers of inflammation and mitochondrial dysfunction were associated with clinical events. Randomization to omit or add NRTIs was not associated with clinical events. sCD14 identifies a group at higher risk of developing clinical events.

Poster Abstracts

CROI 2020 263