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Unlabelled: A few studies have assessed the observed fibrosis progression between serial liver biopsies (LB) in human immunodeficiency virus (HIV) / hepatitis C virus (HCV)-coinfected patients. Approximately half of the patients progressed at least one fibrosis stage over a short period of time. The risk factors for this fast progression need clarification. Because of this, we evaluated the observed fibrosis progression rates of HIV/HCV-coinfected patients and the risk factors for accelerated progression. Overall, 135 HIV-infected patients with positive serum HCV RNA, without other possible causes of liver disease, who underwent two LB, separated at least by 1 year, were included in this retrospective cohort study. The median (Q1-Q3) time between both LBs was 3.3 (2.0-5.2) years. Patients showed the following changes in fibrosis stage: regression >or =1 stage: 23 (17%), no change: 52 (39%), progression 1 stage: 38 (28%), and progression > or =2 stages: 22 (16%). Seventeen (13%) patients had cirrhosis in the second biopsy. Factors independently associated with progression > or =1 stage were undetectable plasma HIV RNA during the follow-up (relative risk [RR] [95% confidence interval, 95% CI] 0.61 [0.39-0.93], P = 0.03), moderate-to-severe lobular necroinflammation (1.77 [1.16-2.7], P = 0.009), time between biopsies (1.11 [1.08-1.2], P = 0.01), and end of treatment response to anti-HCV therapy (0.41 [0.19-0.88], P = 0.02)., Conclusion: Fibrosis progresses with high frequency in HIV/HCV-coinfected patients over a period of time of 3 years. Absent-to-mild lobular necroinflammation at baseline, achievement of response with anti-HCV treatment, and effective antiretroviral therapy are associated with slower fibrosis progression.

We describe and characterize an exceptionally large HIV-1 subtype B transmission cluster occurring in the Comunidad Valenciana (CV, Spain). A total of 1806 HIV-1 protease-reverse transcriptase (PR/RT) sequences from different patients were obtained in the CV between 2004 and 2014. After subtyping and generating a phylogenetic tree with additional HIV-1 subtype B sequences, a very large transmission cluster which included almost exclusively sequences from the CV was detected (n = 143 patients). This cluster was then validated and characterized with further maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. With these analyses, the CV cluster was delimited to 113 patients, predominately men who have sex with men (MSM). Although it was significantly located in the city of Valencia (n = 105), phylogenetic analyses suggested this cluster derives from a larger HIV lineage affecting other Spanish localities (n = 194). Coalescent analyses estimated its expansion in Valencia to have started between 1998 and 2004. From 2004 to 2009, members of this cluster represented only 1.46% of the HIV-1 subtype B samples studied in Valencia (n = 5/143), whereas from 2010 onwards its prevalence raised to 12.64% (n = 100/791). In conclusion, we have detected a very large transmission cluster in the CV where it has experienced a very fast growth in the recent years in the city of Valencia, thus contributing significantly to the HIV epidemic in this locality. Its transmission efficiency evidences shortcomings in HIV control measures in Spain and particularly in Valencia. [ABSTRACT FROM AUTHOR]

We found that FIB-4 index outperformed liver biopsy as a predictor of both overall death and liver-related events. Our results call into question the role of liver biopsy as a gold standard for assessing prognosis in HIV/hepatitis C virus coinfection.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. [ABSTRACT FROM PUBLISHER]

Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)–coinfected patients with advanced fibrosis, without cirrhosis, are at risk of liver decompensations from the first year after the staging of fibrosis. Therapy against HCV without delay is warranted for patients with precirrhosis and HIV coinfection.Background. Most human immunodeficiency virus (HIV)/hepatitis C virus (HCV)–infected patients who are currently receiving boceprevir or telaprevir-based therapy against HCV show cirrhosis. However, the risk of liver decompensation (DC) among HIV/HCV-coinfected patients with stage 3 fibrosis in the short term could be high enough to not allow delays. We aimed at assessing the risk of DC among HIV/HCV-coinfected individuals with advanced fibrosis (F3–F4).Methods. Eight hundred ninety-two HIV/HCV-coinfected patients, naive or without sustained virologic response to HCV therapy, were included in this cohort. Fibrosis was staged by biopsy in 317 patients and by liver stiffness measurement (LSM) in 575 individuals. Precirrhosis was defined as an LSM of 9.5–14.6 kilopascals (kPa), and cirrhosis as an LSM of ≥14.6 kPa.Results. For patients with biopsy, the probability of remaining free of DC for F3 vs F4 was 99% (95% confidence interval [CI], 95%–100%) vs 96% (95% CI, 91%–98%) at 1 year, and 98% (95% CI, 94%–100%) vs 87% (95% CI, 81%–92%) at 3 years. The only factor independently associated with DC was fibrosis stage (F4 vs F3, subhazard ratio [SHR], 2.1; 95% CI, 1.07–4.1; P = .032). For patients with LSM, the probability of remaining free of DC for precirrhosis vs cirrhosis was 99% (95% CI, 96%–100%) vs 93% (95% CI, 89%–96%) at 1 year, and 97% (95% CI, 94%–99%) vs 83% (95% CI, 77%–87%) at 3 years. Factors independently associated with DC were platelet count (<100 × 103 vs ≥100 × 103: SHR, 1.86; 95% CI, 1.01–3.42; P = .046) and LSM (cirrhosis vs precirrhosis: SHR, 5.67; 95% CI, 2.27–14.1; P < .0001).Conclusions. As in patients with cirrhosis, immediate therapy against HCV is warranted for patients with precirrhosis and HIV coinfection, as they are at risk of DC soon after the diagnosis of advanced fibrosis. [ABSTRACT FROM AUTHOR]

We report that the incidence of hepatocellular carcinoma (HCC) is increasing in human immunodeficiency virus (HIV)–infected patients in Spain. Thus, the incidence of HCC in HIV/hepatitis C virus–coinfected patients increased from 0.2 cases per 1000 person-years in 2000 to 2.8 cases per 1000 person-years in 2009.Background. To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)–infected patients in Spain.Methods. All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented.Results. Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31–227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate.Conclusions. HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary. [ABSTRACT FROM AUTHOR]

Summary: Objective: To assess the frequency of severe liver toxicity in HIV/hepatitis C (HCV)-coinfected patients with advanced liver fibrosis receiving efavirenz (EFV)-based antiretroviral combinations. Methods: One hundred and eighty-nine previously antiretroviral naïve, HIV/HCV-coinfected patients, who started a regimen including two nucleoside analogues plus EFV, and in whom the presence or absence of advanced liver fibrosis could be established, were retrospectively analyzed. Liver fibrosis was evaluated according to a stepwise algorithm including liver biopsy, transient elastography and FIB-4 index. Results: Fifty-six patients had advanced fibrosis – 25 with cirrhosis – and 133 did not. Three (5.4%) subjects with and 9 (6.8%) (p =0.717) without advanced fibrosis developed grade 3–4 transaminase elevation (TE). Grade 4 total bilirubin elevation was seen in 5 (8.9%) patients with advanced fibrosis and in 1 (0.8%) without it (p =0.003). Liver events led to EFV discontinuation in 10 (5.3%) patients, 6 (10.7%) with and 4 (3%) without advanced fibrosis (p =0.031). Conclusions: The hepatic tolerability of EFV was good in HIV/HCV-coinfected patients with advanced liver fibrosis. The frequency of grade 3–4 TE was similar to that observed in patients without advanced fibrosis, there was no death attributable to liver failure caused by drug toxicity and the rate of EFV discontinuations due to liver events was low. [ABSTRACT FROM AUTHOR]

Enveloped viruses induce cell-cell fusion when infected cells expressing viral envelope proteins interact with target cells, or through the contact of cell-free viral particles with adjoining target cells. CD4 + T lymphocytes and cells from the monocyte-macrophage lineage express receptors for HIV envelope protein. We have previously reported that lymphoid Jurkat T cells expressing the HIV-1 envelope protein (Env) can fuse with THP-1 monocytic cells, forming heterokaryons with a predominantly myeloid phenotype. This study shows that the expression of monocytic markers in heterokaryons is stable, whereas the expression of lymphoid markers is mostly lost. Like THP-1 cells, heterokaryons exhibited FcγR-dependent phagocytic activity and showed an enhanced expression of the activation marker ICAM-1 upon stimulation with PMA. In addition, heterokaryons showed morphological changes compatible with maturation, and high expression of the differentiation marker CD11b in the absence of differentiation-inducing agents. No morphological change nor increase in CD11b expression were observed when an HIV-fusion inhibitor blocked fusion, or when THP-1 cells were cocultured with Jurkat cells expressing a non-fusogenic Env protein, showing that differentiation was not induced merely by cell-cell interaction but required cell-cell fusion. Inhibition of TLR2/TLR4 signaling by a TIRAP inhibitor greatly reduced the expression of CD11b in heterokaryons. Thus, lymphocyte-monocyte heterokaryons induced by HIV-1 Env are stable and functional, and fusion prompts a phenotype characteristic of activated monocytes via intracellular TLR2/TLR4 signaling. [ABSTRACT FROM AUTHOR]

This study assesses the incidence of hepatocellular carcinoma (HCC) in a prospective cohort of HIV-infected patients, the majority receiving antiretroviral therapy, with liver cirrhosis from different etiologies, enrolled between 2004 and 2005 with median follow-up of 5 years. We followed 371 patients, 25.6% with decompensated cirrhosis at baseline. The incidence rate of HCC was 6.72 per 1000 person-years [95% confidence interval (CI): 2.6 to 10.9]. There was a trend toward a higher cumulative probability of developing HCC at 6 years of follow-up (considering death and liver transplant as competing risks) in patients with decompensated versus compensated cirrhosis at baseline (6% vs. 2%, P < 0.06). [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the effectiveness of switching nevirapine (NVP) twice a day to once a day. Result shows that patients on standard twice daily NVP-containing regimens showed that switching to once a day NVP was not inferior to continue twice daily NVP, in terms of the predefined noninferiority margin of 10% for hepatotoxicity for at least 12-18 weeks.

The article reports on the description of patients characteristics and natural history of the patients diagnosed with HIV-related osteonecrosis in Spain. Osteonecrosis is avascular necrosis of the bone, a disabling condition that has been increasingly described in the setting of HIV infection since its first reported case in the early 1990. The case was diagnosed from 1990 through 2003 in 19 Spanish clinics. HIV-related osteonecrosis is associated with significant disability over time.