CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Results: 18,060 participants were followed over a total of 92,059 person-years (PY). During follow-up, 5412 participants developed chronic LEE (incidence 5.88/100 PY [95% CI 5.72-6.04]). Chronic LEE was associated with ongoing exposure to regimens containing didanosine (<2yrs RR 1.26 [1.08-1.45], >2yrs 1.27 [1.14-1.43]); stavudine (<2yrs 1.51 [1.26- 1.82], >2yrs 1.17 [1.04-1.33]); tenofovir (<2yrs 1.57 [1.41-1.75], >2yrs 1.17 [1.04-1.33]); emtricitabine (<2yrs 1.17 [1.03-1.32], >2yrs 1.0 [0.86-1.18]); nevirapine (<2yrs 1.41 [1.25- 1.58], >2yrs 1.01 [0.91-1.13]); and efavirenz (<2yrs 1.13 [1.02-1.25], >2yrs 0.81 [0.73-0.90]). Because the association of tenofovir with LEE was unexpected, we further analysed commonly used tenofovir-containing-regimens. The results are depicted in the figure. No evidence for an association with increased risk was found for lamivudine (<2yrs 0.88 [0.75-1.02], >2yrs 0.98 [0.87-1.11]); abacavir (<2yrs 1.08 [0.97-1.21], >2yrs 0.91 [0.83-1.01]); and all tested PIs, including lopinavir (<2yrs 0.81 [0.67-0.97], >2yrs 0.83 [0.70-0.99]), atazanavir (<2yrs 1.10 [0.94-1.28], >2yrs 0.72 [0.60-0.86]), darunavir (<2yrs 0.65 [0.51-0.84], >2yrs 0.53 [0.37-0.76]) and ritonavir (<2yrs 0.58 [0.49-0.68], >2yrs 0.79 [0.68-0.91]).

Conclusions: Whilst didanosine, stavudine, nevirapine and efavirenz have been described to be hepatotoxic, we additionally observed an association between tenofovir and chronic LEE emerging within first 2 years after drug initiation. The results are consistent with other small case studies. The reasons for and clinical implications from this novel tenofovir-LEE signal should be investigated. 806 APRI and FIB4: AssociatedWith D-Drug Exposure, Low CD4 Count and Monocyte Activation KatherineW. Kooij 1 ; Rosan van Zoest 1 ; FerdinandW.Wit 1 ; Judith Schouten 2 ; Neeltje Kootstra 2 ; Ineke G. Stolte 3 ; Maria Prins 3 ; Peter Reiss 1 ; Marc van derValk 2 AGEhIV Cohort Study Group 1 Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands; 2 Academic Medical Center University of Amsterdam, Amsterdam, Netherlands; 3 Public Health Service of Amsterdam, Amsterdam, Netherlands Background: Previous studies have suggested that HIV may be independently associated with liver fibrosis in the absence of chronic hepatitis B or C virus (HBV/HCV) coinfection. Methods: We compared the prevalence of liver fibrosis, estimated by using APRI and FIB4 scores, in virologically suppressed HIV-infected (HIV-RNA <200c/mL in prior year) and HIV-uninfected participants of the AGE h IV Cohort Study, aged ≥ 45 yrs, all without detectable plasma HBsAg and HCV RNA. The association between HIV and log 10 transformed APRI [AST(U/L)/40]x[ 100/platelet count (PLT)(10 9 cells/L)] and FIB4 [age(yrs)xAST(U/L)]/ [PLT(10 9 cells/L)xALT 1/2 (U/L)] scores was investigated by multivariable regression, adjusting for demographic/behavioral covariates, and exploring soluble (s)CD163, sCD14, immunodeficiency and ART exposure as possible determinants. Results: The prevalence of liver fibrosis (APRI>1.5/FIB4>3.25) was low in both groups, though median values of both scores were significantly higher in HIV-positive individuals (Table). After adjustment for age, gender, ethnicity, heavy alcohol intake, detectable anti-HCV/anti-HBc (as markers of past infection) and BMI, we found that HIV was no longer significantly associated with logFIB4, but the association with logAPRI remained significant (+0.07, 95%CI 0.02–0.13, p=0.007). Higher sCD163 was independently associated with a higher logAPRI in the combined group (+0.03/100ng/mL, 95%CI 0.02–0.05, p<0.001), but with logFIB4 in the HIV-positive group only (+0.03/100ng/mL, 95%CI 0.01–0.05, p=0.005). sCD14 was not associated with either logAPRI or logFIB4. Within the HIV-positive group both a lower current CD4 count and longer exposure to d-drugs (ddI, ddC, d4T) were independently associated with both a higher logAPRI (CD4 count: +0.02/100cells, 95%CI 0.01– 0.04, p=0.003, d-drugs: +0.02/yr, 95%CI 0.01–0.03, p<0.001) and logFIB4 (CD4 count: +0.03/100cells, 95%CI 0.02–0.04, p<0.001, d-drugs: +0.01/yr, 95%CI 0.00–0.02, p=0.002). Prior AIDS and nadir CD4 count were not associated with logAPRI or logFIB4.

Poster Abstracts

Conclusions: HIV infection was independently associated with a higher APRI, but not with FIB4, in virologically suppressed HIV-infected persons compared to HIV-uninfected controls, all without chronic HBV/HCV coinfection. The association between sCD163 and APRI/FIB4 may suggest a role for activated intrahepatic macrophages in liver fibrosis. Prior d-drug exposure and ongoing immunodeficiency were identified as additional contributors to liver fibrosis.

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CROI 2015