Liver stiffness change with HCV cure in HIV-infected patients on non-nucleoside analogues.

BACKGROUND: Liver stiffness (LS) at sustained viral response (SVR) is strongly associated with a lower incidence of subsequent hepatic events. HIV NNRTIs may have a beneficial impact on fibrogenesis. OBJECTIVES: Our aim was to analyse the influence of NNRTI-based therapy on the change in LS from starting direct-acting antiviral (DAA) therapy to achieving SVR in HIV/HCV-coinfected patients. METHODS: Three hundred and thirteen HIV/HCV-coinfected patients who fulfilled the following criteria were included: (i) had achieved SVR with an IFN-free, DAA-including regimen; (ii) LS ≥9.5 kPa before therapy; (iii) LS measurement available at SVR; (iv) seronegative for HBsAg; and (v) ART containing 2 NRTIs plus either 1 NNRTI or 1 integrase inhibitor (INI) or 1-2 NRTIs plus 1 PI. LS changes were assessed. RESULTS: Seventy-four patients received NNRTI-based combinations [53 (71.6%) rilpivirine and 16 (21.6%) efavirenz] and 239 patients received other regimens. At baseline, the median (IQR) LS was 16.7 kPa (11.8-25.6) in the NNRTI group and 17.3 kPa (11.9-27.4) in the non-NNRTI group (P = 0.278). The median (IQR) percentage of LS decrease from baseline to SVR was 35.2% (18.2%-52.3%) for NNRTI-based therapy and 29.5% (10%-45.9%) for PI- or INI-based therapy (P = 0.018). In multivariate analysis, adjusted for sex, age, HCV genotype, NRTI backbone and propensity score for HIV therapy, NNRTI-based regimen use was associated with a higher LS decrease [ß = 11.088 (95% CI = 1.67-20.51); P = 0.021]. CONCLUSIONS: Treatment with NNRTI plus 2 NRTI combinations is associated with a higher LS decline than other ART combinations in HIV/HCV-coinfected patients receiving DAA-based therapy.

Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals.

BACKGROUND: Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). METHODS: In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication-hepatic decompensation or hepatocellular carcinoma (HCC)-or requiring liver transplant after SVR. RESULTS: During a median (Q1-Q3) follow-up of 31.6 (22.7-36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28-9.12]), pretreatment CPT class B or C (62.5 [3.08-1246.42]) and MELD scores (1.37 [1.03-1.82]), CPT class B or C at SVR (10.71 [1.32-87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49-13.15]), FIB-4 index at SVR (1.39 [1.13-1.70]), and LS at SVR (1.05 [1.02-1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. CONCLUSIONS: LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

Transmitted drug resistance to rilpivirine in newly diagnosed antiretroviral naive adults.

We characterized transmitted drug resistance to rilpivirine and the predicted efficacy of first-line rilpivirine-containing regimens in antiretroviral-naive Spanish patients. International Antiviral Society-USA mutations were detected in 138 of 2781 patients (4.9%), E138A (3.4%) being the most prevalent. Using the Stanford Algorithm, 121 patients (4.4%) showed low-level or intermediate resistance. No differences in the predicted efficacy of first-line non-nucleoside reverse transcriptase inhibitor-based regimens were observed. As rilpivirine becomes more widely used in clinical practice, the evolution of its transmitted drug resistance will need to be monitored. In addition, the exact role of E138A singletons on rilpivirine activity as part of first-line regimens merits further evaluation.

Lack of short-term increase in serum mediators of fibrogenesis and in non-invasive markers of liver fibrosis in HIV/hepatitis C virus-coinfected patients starting maraviroc-based antiretroviral therapy.

The aim of this study was to analyze serum changes in mediators of fibrogenesis and in non-invasive markers of liver fibrosis among HIV/HCV-coinfected patients starting maraviroc (MVC)-based antiretroviral therapy. Patients included in this prospective pilot study met the following criteria: (1) HIV-infection, (2) detectable serum HCV-RNA, and ((3) started MVC. Transforming growth factor-ß1 (TGF-beta1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured in serum samples at baseline and 6 months after starting MVC. AST-to-platelet ratio index (APRI) was assessed at the same time points. Twenty-four patients were analyzed. Median (IQR) serum levels at baseline and after 6 months on MVC of TGF-beta1 were 27,295 (20,562-36,844) and 33,753 (18,973-46,130) pg/mL (p=0.116), of MMP-2 were 216 (186-274) and 241 (194-306) ng/mL (p=0.247), and of TIMP-1 were 237 (170-284) and 216 (171-271) ng/mL (p=0.415). APRI levels were 0.99 (0.53-3.46) at baseline and 0.83 (0.48-2.34) at 6 months (p=0.16). Serum mediators of liver fibrogenesis and fibrosis do not change significantly in HIV/HCV-coinfected patients in the short-term after starting MVC. As TGF-beta1 levels have been shown to increase over time in HCV infection and liver fibrosis worsens rapidly in HIV/HCV coinfection, these parameters seem to evolve in a different way in MVC-treated patients.