Effects of Hepatitis C Virus (HCV) Eradication on Bone Mineral Density in Human Immunodeficiency Virus/HCV-Coinfected Patients.

BACKGROUND: Little is known about the effects of eradication of hepatitis C virus (HCV) on bone mineral density (BMD) and biomarkers of bone remodeling in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization BMD categories at both sites, and plasma concentrations of soluble receptor activator of NF-κß ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. RESULTS: A total of 238 patients were included. The median age was 49.5 years, 76.5% were males, 48.3% had cirrhosis, 98.3% were on antiretroviral therapy, median CD4+ cell count was 527 cells/µL, and 86.6% had HIV-1 RNA <50 copies/mL. The prevalence of osteoporosis at baseline at the lumbar spine (LS) and femoral neck (FN) was 17.6% and 7.2%, respectively. Anti-HCV therapy comprised pegylated interferon (peg-IFN) and ribavirin (RBV) plus 1 direct-acting antiviral in 53.4%, peg-IFN/RBV in 34.5%, and sofosbuvir/RBV in 12.2%. A total of 145 (60.9%) patients achieved sustained virologic response (SVR). No significant effect of SVR was observed on sBMD for the interaction between time and SVR either in the LS (P = .801) or the FN (P = .911). Likewise, no significant effect of SVR was observed in plasma levels of sRANKL (P = .205), OPG (P = .249), or sRANKL/OPG ratio (P = .123) for the interaction between time and SVR. No significant correlation was found between fibrosis by transient elastography, and LS and FN sBMD, at baseline and week 96. CONCLUSIONS: SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). CONCLUSION: Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356).

Comparison of the prognostic value of liver biopsy and FIB-4 index in patients coinfected with HIV and hepatitis C virus.

BACKGROUND: We compared the prognostic value of liver biopsy (LB) and FIB-4 index in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. METHODS: We studied patients from the Grupo de Estudio del SIDA 3603 study cohort, in whom fibrosis was evaluated at baseline using both LB (Metavir score) and FIB-4 index. We assessed overall death (OD) and liver-related events (LREs), defined as decompensation or hepatocellular carcinoma, whichever occurred first. We used receiver operating characteristic (ROC) curves to determine the ability of LB and FIB-4 to predict outcomes. We also assessed the association between advanced fibrosis-LB (F3 or greater) or FIB-4 (≥3.25)-and outcomes using multivariate Cox regression analysis. RESULTS: The study sample comprised 903 patients (328 with sustained virologic response [SVR]). Baseline fibrosis by LB was as follows: F0, n = 71; F1, n = 242; F2, n = 236; F3, n = 236; F4, n = 118. Fibrosis by FIB-4 was as follows: ≤1, n = 148; >1 to <3.25, n = 597; ≥3.25, n = 158. After a median follow-up of 62 months, there were 46 deaths and 71 LREs. The area under the ROC curves for OD/LREs was 0.648 and 0.742 for LB and FIB-4, respectively (P = .006). Similar results were found for patients without SVR and for OD and LREs separately. The adjusted hazard ratios of OD or LRE were 1.740 (95% confidence interval [CI], 1.119-2.7.06; P = .014) for advanced fibrosis assessed by LB and 3.896 (95% CI, 2.463-6.160; P < .001) assessed by FIB-4. CONCLUSIONS: FIB-4 outperformed LB as a predictor of OD and LRE. These findings are of relevance for clinical practice and research and call into question the role of LB as a gold standard for assessing prognosis in HIV/HCV coinfection.

Effects of sustained viral response in patients with HIV and chronic hepatitis C and nonadvanced liver fibrosis.

OBJECTIVE: We assessed the effects of sustained viral response (SVR), after treating with interferon-ribavirin (IF-RB), on mortality, liver-related (LR) events (decompensation, hepatocellular carcinoma), HIV progression, and liver stiffness in HIV/hepatitis C virus (HCV)-coinfected patients with nonadvanced liver fibrosis. METHODS: From a cohort of HIV/HCV-coinfected patients treated with IF-RB, we selected those with baseline liver fibrosis stages F0, F1, or F2 according to METAVIR. The study started when IF-RB was stopped and ended at death or at the last follow-up visit. RESULTS: A total of 695 patients were included (HCV genotype 1 or 4, 431; F0, 77; F1, 290; and F2, 328), and 274 patients achieved SVR. After a median follow-up of 4.9 years, the adjusted hazard ratio (aHR) [95% confidence interval (CI)] of LR events or overall death, for patients with SVR taking the group of patients with no SVR as a reference was 0.217 (0.079 to 0.599) (P = 0.003) for the whole cohort with F0 to F2. For patients with F0, the aHR (95% CI) was 0.514 (0.040 to 6.593) (P = 0.609), for patients with F1, the aHR (95% CI) was 0.305 (0.053 to 1.762) (P = 0.185), and for patients with F2, it was 0.075 (0.009 to 0.662) (P = 0.020). We also found that, in comparison with no SVR, SVR was followed by less frequent HIV progression for the entire population (F0 to F2) and less frequent liver stiffness across all categories of fibrosis. CONCLUSIONS: SVR in HIV/HCV-coinfected patients with moderate stages of liver fibrosis is associated with a reduction of mortality and LR events, and with a reduction of progression of HIV and liver fibrosis.

Results of treatment with doxorubicin, bleomycin, vinblastine and dacarbazine and highly active antiretroviral therapy in advanced stage, human immunodeficiency virus-related Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: Although doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is considered the standard chemotherapy regimen for Hodgkin's lymphoma (HL), information on the results of this therapy in human immunodeficiency (HIV)-related HL is scarce. We analyzed the results of the ABVD regimen and highly active antiretroviral therapy (HAART) in patients with advanced stage, HIV-related HL. DESIGN AND METHODS: From January 1996 to December 2005, 62 HIV-infected patients with newly diagnosed HL were treated in 15 Spanish hospitals. Six to eight cycles of ABVD and HAART were planned. Response to chemotherapy, overall survival (OS) and event-free survival (EFS) were recorded. RESULTS: The median age of the patients was 37 years (range, 24-61) and 29 (47%) had a previously known diagnosis of acquired immunodeficiency syndrome. The median CD4 lymphocyte count at diagnosis was 129/muL (range 5-1,209). The histologic subtype of HL was nodular sclerosis in 17 patients (27%), mixed cellularity in 25 (41%), lymphocyte depletion in 10 (16%) and non-specified in the remaining 10 (16%). Twenty-one (34%) patients were in stage III and 41 (66%) in stage IV. The scheduled six to eight ABVD cycles were completed in 82% of cases. Six patients died during induction, 54 (87%) achieved a complete response (CR) and two were resistant. After a median follow-up of 39 and 47 months, 5-year EFS and OS probabilities were 71% (47-95) and 76% (65-87), respectively. An immunological response was observed in 24 out of 43 patients (56%) and a virological response in 27 out of 40 (68%). The immunological response to HAART had a positive impact on OS and EFS (p=0.002 and p=0.001, respectively). INTERPRETATION AND CONCLUSIONS: In patients with advanced stage, HIV-related HL, treatment with ABVD together with HAART is feasible and effective. This supports the concept that patients with HIV-related HL should be treated in the same way as immunocompetent patients if HAART, adequate supportive therapy and anti-infectious prophylaxis are given concomitantly. An immunological response to HAART has a positive impact on OS and EFS.