Response to direct-acting antiviral therapy among ongoing drug users and people receiving opioid substitution therapy.

BACKGROUND & AIMS: People who inject drugs (PWID) and are on opioid agonist therapy (OAT) might have lower adherence to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and, therefore, lower rates of sustained virologic response (SVR). Because of this, we compared the SVR rates to interferon-free DAA combinations in individuals receiving OAT and those not receiving OAT in a real-world setting. METHODS: The HEPAVIR-DAA cohort, recruiting HIV/HCV-coinfected patients (NCT02057003), and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are ongoing prospective multicenter cohorts of patients receiving DAAs in clinical practice. We compared SVR 12 weeks after treatment (SVR12) in non-drug users and PWID, including those receiving or not receiving OAT. Intention-to-treat and per protocol analyses were performed. RESULTS: Overall, 1,752 patients started interferon-free DAA treatment. By intention-to-treat analysis, 778 (95%, 95% CI 93%-96%) never injectors, 673 (92%, 95% CI 89%-93%) PWID not on OAT and 177 (89%, 95% CI 83%-92%) PWID on OAT achieved SVR12 (p = 0.002). SVR12 rates for ongoing drug users (with or without OAT) were 68 (79%) compared with 1,548 (95%) for non-drug users (p <0.001). Among ongoing drug users, 15 (17%) were lost-to-follow-up, and 3 (3.5%) became reinfected. In the per protocol analysis, 97% never injectors, 95% PWID not on OAT and 95% PWID on OAT achieved SVR12 (p = 0.246). After adjustment, ongoing drug use was associated with SVR12 (intention-to-treat) and OAT use was not. CONCLUSIONS: HCV-infected PWID achieve high SVR12 rates with DAAs whether they are on OAT or not, but their response rates are lower than those of patients who never used drugs. This is mainly attributable to more frequent loss to follow-up. Accounting for active drug use during DAA therapy nearly closed the gap in SVR rates between the study groups. LAY SUMMARY: Patients with hepatitis C virus infection who are on opioid agonist therapy can achieve high cure rates with current treatments. The use of illicit drugs during treatment can drive drop-outs and reduce cure rates. However, hepatitis C can be cured in most of those using drugs who complete treatment and follow-up. Clinical trial number: HEPAVIR-DAA cohort, NCT02057003; GEHEP-MONO cohort, NCT02333292.

Sustained virological response to direct-acting antiviral regimens reduces the risk of hepatocellular carcinoma in HIV/HCV-coinfected patients with cirrhosis.

Objectives: To assess the impact of all-oral direct-acting antiviral agent (DAA) regimens on the risk of hepatocellular carcinoma (HCC) in HIV/HCV-coinfected patients with cirrhosis. Methods: This was a multicentre prospective cohort study recruiting HIV/HCV-coinfected patients with a new diagnosis of compensated cirrhosis. Patients were followed up until HCC, death or the censoring date (March 2017). The primary endpoint was the emergence of HCC. The incidence rate (IR) (95% CI) of HCC in different groups was computed. Time-to-event analyses were performed to identify predictors of HCC emergence. Results: The study included 495 HIV/HCV-coinfected patients with cirrhosis. After a median (IQR) follow-up of 59 (27-84) months, 22 (4.4%; 95% CI 2.6-6.3) patients developed an HCC. The IR (95% CI) of HCC was 0.93 (0.06-1.42) per 100 person-years (PY). Three hundred and three (61%) patients achieved sustained virological response (SVR) during follow-up, 79 after interferon (IFN)-based regimens and 224 after an all-oral DAA regimen. The IR (95% CI) of HCC after all-oral DAA was 0.35 (0.14-0.85) per 100 PY whereas it was 1.79 (1.11-2.88) per 100 PY in the remaining cohort (P = 0.0005). When only patients with SVR were considered, the IR (95% CI) of HCC after all-oral DAA was 0.32 (0.12-0.86) whereas it was 0 per 100 PY among those with SVR after IFN-based therapies (P = 0.27). Achieving SVR with an all-oral DAA regimen during follow-up was independently associated with a lower risk of HCC emergence (subhazard ratio 0.264; 95% CI 0.070-0.991; P = 0.049). Conclusions: SVR with all-oral DAA regimens reduces the risk of HCC in HIV/HCV-coinfected patients with compensated cirrhosis.

Paritaprevir/ritonavir/ombitasvir plus dasabuvir in HIV/HCV-coinfected patients with genotype 1 in real-life practice.

Background Data on the efficacy, safety, and concomitant use with other drugs of the combination ritonavir-boosted paritaprevir/ombitasvir plus dasabuvir (PrOD) in HIV/HCV-coinfected patients in real life are limited. The objectives of this study were to analyze these topics in HIV/HCV-coinfected subjects bearing HCV genotype 1 (GT1). Methods One hundred and eighty-two HIV/HCV-coinfected patients with GT1 (87 1a, 71 1b, 23 other) treated with PrOD, plus ribavirin (RBV) in 119 cases, in routine clinical practice were analyzed. The main variable of efficacy was sustained virological response (SVR) 12 weeks after completing therapy in an intention-to-treat (ITT) analysis and that of safety treatment discontinuation because of adverse effects. Factors associated with SVR were analyzed with a modified ITT (mITT) strategy. Results One hundred and seventy-two (94%) patients attained SVR, 3 (2%) experienced a relapse and two (1%) discontinued therapy due to adverse events. The rates of SVR in subjects with GT 1a and 1b by mITT were, respectively, 97% and 98%. Sixty-five (98%) out of 66 patients with cirrhosis and 107 (98%) out of 110 (p = 1) non-cirrhotics achieved SVR. Fifty-five (95%) patients on concomitant darunavir therapy developed SVR vs. 117 (99%) (p = 0.105) of those without DRV. RBV dose was reduced in 13 (11%) patients and permanently discontinued in 2 (2%), with no impact on SVR. Conclusions PrOD is highly effective and well tolerated in HIV/HCV-coinfected patients with GT1 in routine clinical practice. RBV is often required. However, RBV dose reduction or discontinuation is uncommonly needed and do not impair the SVR rate.

Changes in Liver Steatosis After Switching From Efavirenz to Raltegravir Among Human Immunodeficiency Virus-Infected Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND: Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. METHODS: HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP. RESULTS: Overall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values <238 dB/m at week 48 were observed in 9 (47%) patients on RAL and 3 (15%) individuals on EFV (P = .029). CONCLUSIONS: After 48 weeks, HIV-infected individuals switching EFV to RAL showed decreases in the degree of hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL. CLINICAL TRIALS REGISTRATION: NCT01900015.

Progression of liver stiffness predicts clinical events in HIV/HCV-coinfected patients with compensated cirrhosis.

BACKGROUND: Our objective was to assess the predictive value of the changes of liver stiffness (LS) for clinical outcome in HIV/HCV-coinfected patients with compensated liver cirrhosis and a LS value < 40 kPa. METHODS: Prospective cohort of 275 HIV/HCV-coinfected patients with cirrhosis, no previous liver decompensation (LD) and LS < 40 kPa. The time from diagnosis to LD and/or hepatocellular carcinoma (HCC) and the predictors of this outcome were evaluated. Significant progression of LS was defined as an increase ≥ 30 % over the baseline value at any time during the follow-up. RESULTS: After a median (Q1-Q3) follow-up of 32 (20-48) months, 19 (6.9 %, 95 % CI: 3.8 %-9.9 %) patients developed a first LD and/or HCC. At the end of the follow-up, 247 (90 %) patients had undergone a further LS examination. Of them, 77 (31 %) patients had a significant progression of LS. The mean (SD) survival time free of LD and/or HCC was 67 (3) and 77 (1) months in patients with or without significant progression of LS (p = 0.01). Significant progression of LS was an independent predictor of LD and/or HCC (Adjusted Hazard Ratio 4.63; 95 % confidence interval: 1.34-16.02; p = 0.015). CONCLUSIONS: Significant progression of LS is associated with a higher risk of clinical events in HIV/HCV-coinfected patients with compensated cirrhosis and LS < 40 kPa.

Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C.

OBJECTIVES: To assess the incidence of hepatitis C virus (HCV) reinfections after therapy-induced clearance in HIV-coinfected patients with prior chronic hepatitis C. METHODS: Eighty-four HIV-infected subjects, who had previously achieved sustained virological response (SVR) after being treated of chronic hepatitis C, were analyzed. In all of them, at least yearly HCV RNA determinations were carried out during a median (range) of 34 (12-146) months. RESULTS: Seventy-two (86%) subjects had been people who inject drugs (PWID), of whom 11 (15%) continued to use snorted or injected drugs during the follow-up. Four (4.76%) patients showed HCV reinfection (incidence 1.21 [95% confidence interval: 0.3-3.09] cases per 100 person-years). These patients maintained risk factors for HCV infection. In three cases, HCV genotype switched. Phylogenetic analysis of the remaining case suggested reinfection from his sexual partner. CONCLUSION: The incidence of HCV reinfection in the overall population of HIV-coinfected patients who achieved SVR after being treated against chronic hepatitis C is low. A low frequency of risk behavior is the main factor accounting for this modest rate of reinfection. The possibility of reinfection should not be considered a reason against treatment of HCV infection with direct acting antivirals in PWID.

Low risk of liver decompensation among human immunodeficiency virus/hepatitis C virus-coinfected patients with mild fibrosis in the short term.

UNLABELLED: Liver fibrosis is used to make decisions about the timing of therapy against hepatitis C virus (HCV) in routine clinical practice, which should be based on the short-term likelihood of liver decompensations. Thus, we aimed at evaluating the risk of decompensations and death among human immunodeficiency virus (HIV)/HCV-coinfected individuals according to their baseline fibrosis classified by either liver biopsy or liver stiffness measurement (LSM). Patients coinfected with HIV/HCV, naive or without sustained virological response to HCV therapy, were included in this cohort. Fibrosis was classified by biopsy in 683 patients and by LSM in 1046 individuals. Reference categories were fibrosis stage 0 and LSM <6 kPa. For patients with biopsy, the adjusted subhazard ratio for decompensations and 95% confidence interval (95% CI) by fibrosis stage were as follows: stage 1, 2.3 (0.27-20.3), P = 0.443; stage 2, 2.8 (0.33-24), P = 0.345; stage 3, 4.91 (0.60-41), P = 0.137; stage 4, 9.89 (1.25-79.5), P = 0.030. For patients with LSM, the adjusted subhazard ratio and 95% CI by LSM category were as follows: 6-9.4 kPa, 1.89 (0.18-20.3), P = 0.599; 9.5-14.5 kPa, 6.59 (0.73-59.2), P = 0.092; ≥14.6 kPa, 59.5 (8.3-427), P < 0.0001. Regarding the risk of death, the adjusted hazard ratio and 95% CI for death by fibrosis stage were as follows: stage 1, 1.3 (0.4-4.11), P = 0.677; stage 2, 2.68 (0.86-8.36), P = 0.090; stage 3, 2.58 (0.82-8.15), P = 0.106; stage 4, 4.35 (1.43-13.3), P = 0.010. For patients with LSM, the adjusted hazard ratio and 95% CI for death by LSM were as follows: 6-9.4 kPa, 1.7 (0.63-4.79), P = 0.288; 9.5-14.5 kPa, 3.38 (1.2-9.5), P = 0.021; ≥14.6 kPa, 12.7 (4.9-33.6), P < 0.0001. CONCLUSION: Patients coinfected with HIV/HCV without advanced fibrosis are at very low risk of decompensations in the short term; deferral of HCV therapy for a few years and monitoring fibrosis progression is a safe option until cheaper, more effective, and more convenient HCV treatment becomes widely available.

Risk of liver decompensation among HIV/hepatitis C virus-coinfected individuals with advanced fibrosis: implications for the timing of therapy.

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 × 10(3) vs ≥100 × 10(3): 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.

Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis.

UNLABELLED: Our aim was to assess the predictive value of liver stiffness (LS), measured by transient elastography (TE), for clinical outcome in human immunodeficiency virus / hepatitis C virus (HIV/HCV)-coinfected patients with compensated liver cirrhosis. This was a prospective cohort study of 239 consecutive HIV/HCV-coinfected patients with a new diagnosis of cirrhosis, done by TE, and no previous decompensation of liver disease. The time from diagnosis to the first liver decompensation and death from liver disease, as well as the predictors of these outcomes, were evaluated. After a median (Q1-Q3) follow-up of 20 (9-34) months, 31 (13%, 95% confidence interval [CI]: 9%-17%) patients developed a decompensation. The incidence of decompensation was 6.7 cases per 100 person-years (95% CI, 4.7-9-6). Fourteen (8%) out of 181 patients with a baseline LS < 40 kPa developed a decompensation versus 17 (29%) out of 58 with LS ≥ 40 kPa (P = 0.001). Factors independently associated with decompensation were Child-Turcotte-Pugh (CTP) class B versus A (hazard ratio [HR] 7.7; 95% CI 3.3-18.5; P < 0.0001), log-plasma HCV RNA load (HR 2.1; 95% CI 1.2-3.6; P = 0.01), hepatitis B virus coinfection (HR, 10.3; 95% CI, 2.1-50.4; P = 0.004) and baseline LS (HR 1.03; 95% CI 1.01-1.05; P = 0.02). Fifteen (6%, 95% CI: 3.5%-9.9%) patients died, 10 of them due to liver disease, and one underwent liver transplantation. CTP class B (HR 16.5; 95% CI 3.4-68.2; P < 0.0001) and previous exposure to HCV therapy (HR 7.4; 95% CI 1.7-32.4, P = 0.007) were independently associated with liver-related death; baseline LS (HR 1.03; 95% CI 0.98-1.07; P = 0.08) was of borderline significance. CONCLUSION: LS predicts the development of hepatic decompensations and liver-related mortality in HIV/HCV-coinfection with compensated cirrhosis and provides additional prognostic information to that provided by the CTP score.

Leishmaniasis visceral con manifestaciones en lengua

Presentamos un caso de Leishmaniasis visceral con manifestaciones en lengua en un paciente inmunocompetente que simulaba una tumoración, pues el espectro clínico de la enfermedad es muy amplio, afectando a distintos órganos con manifestaciones distintas en dependencia de la especie que parasita y de la inmunocompetencia del huésped. Se hace una revisión en la literatura de las características de dicha patología. (AU)