Antonio Rivero

Benefits From Sustained Virologic Response to Pegylated Interferon Plus Ribavirin in HIV/Hepatitis C Virus–Coinfected Patients With Compensated Cirrhosis

BACKGROUND The objective of this study was to determine the impact of sustained virologic response (SVR) to pegylated interferon (peg-IFN) plus ribavirin (RBV) on the incidence of liver-related complications and overall mortality in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS We included in this prospective cohort study 166 coinfected patients with compensated cirrhosis, who received peg-IFN plus RBV, to assess the time from the starting date of HCV therapy to the first hepatic decompensation and death due to any cause. RESULTS SVR was observed in 43 (25%) individuals. Two (4.6%) patients with SVR developed liver decompensation vs 33 (26.8%) individuals without SVR (P = .002). The incidence of liver-related complications was 0.89 cases per 100 person-years (95% confidence interval [CI], .11-3.1) in SVR patients and 6.4 cases per 100 person-years (95% CI, 4.5-8.9) in non-SVR patients. Factors independently associated with liver decompensation were non-SVR (hazard ratio [HR], 8.1; 95% CI, 1.08-61.5; P = .042) and MELD score ≥9 at baseline (HR, 2.9; 95% CI, 1.2-7.2; P = .016). Two (4.6%) patients with SVR died due to any cause compared with 22 (17.9%) individuals without SVR (P = .02). MELD score ≥9 (HR, 3.1; 95% CI, 1.3-7.7; P = .011) and non-SVR (HR, 8.0; 95% CI, 1.07-61; P = .043) were independently associated with overall mortality. CONCLUSIONS The achievement of SVR following peg-IFN plus RBV markedly reduces the incidence of liver-related decompensation and the overall mortality in HIV/HCV-coinfected patients with compensated cirrhosis.

Indirect effects of cytomegalovirus infection in solid organ transplant recipients

Cytomegalovirus (CMV) infection is an important and frequent complication in solid organ transplant (SOT) recipients. This infection causes direct effects by viral inclusion in the cells of various tissues, as well as indirect effects by interaction between low levels of viremia and the host immune response. These indirect effects, such as increased incidence of graft rejection and opportunistic infections or decreased recipient survival, can be as severe as the direct effects, and thus require implementation of preventative practice guidelines. Universal prophylaxis against CMV has shown to be effective for preventing CMV disease and asymptomatic CMV replication, and can be considered the treatment of choice for preventing the indirect effects of this infection.

Prevalence and risk factors for abnormal liver stiffness in HIV-infected patients without viral hepatitis coinfection: role of didanosine.

BACKGROUND Unexpected cases of severe liver disease in HIV-infected patients have been reported and an association with didanosine (ddI) has been suggested. Transient elastography (TE) might detect patients harbouring such a condition. Our objective was to search for the presence of abnormal liver stiffness (LS) in a cohort of HIV-infected patients without HBV or HCV coinfection and to assess the related factors. METHODS A cross-sectional prospective study was conducted. LS was assessed by TE in 258 HIV-infected patients without HBV or HCV coinfection and with no evidence of acute hepatotoxicity or other origins of liver disease. LS values > or =7.2 kPa were considered abnormal. Multivariate analyses were performed to identify factors associated with abnormal LS. RESULTS Abnormal LS was observed in 29 (11.2%) patients. A total of 18 (16.4%) patients previously treated with ddI and 11 (7.4%) of those who never received ddI had LS values > or =7.2 kPa (P=0.02). The prevalence of abnormal LS was higher in patients previously treated with abacavir than in those who had never received abacavir (15 [21.7%] versus 14 [7.4%]; P=0.001). After multivariate analyses, age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.002-1.1; P=0.004) alcohol intake >50 g/day (AOR 7.2, 95% CI 2.6-19.7; P<0.0001), CD4(+) T-cell count <200 cells/ml (AOR 3.4, 95% CI 1.06-11.007; P=0.03), time on ddI treatment (AOR 1.31, 95% CI 1.12-1.52; P=0.001) and previous abacavir exposure (AOR 3.01, 95% CI 1.18-7.67; P=0.02) were independently associated with abnormal LS. CONCLUSIONS The prevalence of abnormal LS in HIV-infected patients without HBV or HCV coinfection is substantial. Long-term exposure to ddI is a major cause of liver damage in these patients.

Simplicity and Efficacy of a Once-Daily Antiretroviral Regimen with Didanosine, Lamivudine, and Efavirenz in Naïve Patients: The VESD Study

Abstract Purpose: Our aim was to analyze the efficacy and safety of didanosine-lamivudine-efavirenz in a cohort of HIV patients starting antiretroviral therapy between January and September 2003. Method: We undertook a prospective, open-label, observational, multicenter study. Results: 163 patients were enrolled. Over a 48-week period, plasma HIV RNA levels declined sharply, with a median decrease at the end of the observation time of >4.62 log copies/mL. The proportion of patients achieving a plasma HIV RNA level below 50 copies/mL was 62.9% (intention-to-treat analysis) at the end of the study period. The mean CD4 cell count increased steadily over time by 199 cells/mL. Antiviral efficacy was similar in patients with a baseline HIV RNA level above or below 100,000 copies/mL. Overall, 57 (34.1%) patients interrupted therapy; 9 due to lack of treatment response, 18 due to adverse side-effects, and 30 patients lost to follow-up or who withdrew their consent. Adherence was very high (90%-95%) and quality of life was good or very good in 69%. Conclusion: The once-daily combination of didanosine-lamivudine-efavirenz resulted in sustained viral suppression and was well-accepted by patients under real-life conditions, even immunosuppressed patients and those with a high viral load. Associated adverse events and virological failures were few.

Different distributions of hepatitis C virus genotypes among HIV‐infected patients with acute and chronic hepatitis C according to interleukin‐28B genotype

The C allele of the single nucleotide polymorphism rs12979860, located near the interleukin‐28B (IL‐28B) gene, has a strong impact on hepatitis C virus (HCV) treatment response, as well as on spontaneous viral clearance. In patients with chronic hepatitis C (CHC), genotype CC carriers harbour HCV genotype 3 more commonly than those with non‐CC genotypes. The aim of this study was to compare the HCV genotype distributions, according to IL‐28B genotype, in HIV‐infected patients with CHC and those with acute hepatitis C (AHC).

Differences in virological response to peginterferon-α plus ribavirin in HIV-positive patients coinfected with HCV subtypes 1a or 1b.

Background:Both viral and host factors influence response to peginterferon-&agr; plus ribavirin (pegIFN&agr;/RBV) in patients with chronic hepatitis C. The impact of these variables is more pronounced in HIV/Hepatitis C virus (HCV)–coinfected individuals, in whom treatment response rates are lower. Methods:Virological responses at multiple time points were assessed in all HIV/HCV-coinfected patients that completed a first course of pegIFN&agr;/RBV. Viral responses were stratified by HCV geno/subtypes and IL28B rs12979860 variants. Results:A total of 331 HIV/HCV-coinfected patients were analyzed. HCV geno/subtype distribution was as follows: HCV-1a in 97, HCV-1b in 62, HCV-3 in 122, and HCV-4 in 50. Age, gender, CD4 counts, plasma HIV RNA and liver fibrosis stage did not differ significantly across HCV geno/subtypes. In contrast, mean serum HCV RNA was greater in HCV-1a compared with the rest (P < 0.0001). The proportion of IL28B CC variants was higher in HCV-3 compared with the rest (P = 0.001). Virological responses were better in HCV-1b than HCV-1a at any given time point during therapy. IL28B variants significantly influenced virological responses across all HCV-1 subtypes, with the strongest effect seen in HCV-1a. In a multivariate linear regression analysis, both HCV-1b and IL28B CC variants were significantly associated with greater HCV RNA drops at weeks 4 (R = 0.52, p < 0.0001) and 12 (R = 0.49, P < 0.0001) of therapy. Conclusions:The response to pegIFN&agr;/RBV therapy is lower in HCV-1a than HCV-1b in HIV/HCV-coinfected patients. The strongest influence of IL28B variants is seen in HCV-1a. This information may be relevant when using most directly acting antivirals in coinfected patients along with pegIFN&agr;/RBV, given that selection of drug resistance occurs more frequently in HCV-1a than HCV-1b.

LDLr genotype modifies the impact of IL28B on HCV viral kinetics after the first weeks of treatment with PEG-IFN/RBV in HIV/HCV patients.

Objective:To evaluate the effect of low-density lipoprotein receptor (LDLr) and IL28B genotypes on hepatitis C virus (HCV) viral kinetics in the first 4 weeks of treatment with pegylated-interferon (PEG-IFN)/ribavirin (RBV) in HIV patients co-infected with HCV genotype 1. Methods:HIV patients co-infected with HCV genotype 1 and naïve to PEG-IFN/RBV treatment were enrolled in a prospective study. HCV RNA viral loads were measured at baseline and at weeks 1, 2 and 4 after start of therapy. Differences in viral load decline were evaluated for IL28B (CC versus non-CC) and LDLr (CC versus non-CC) genotypes between baseline and weeks 1, 2 and 4. Additionally, the effect of LDLr genotype on HCV viral decline in IL28B CC genotype patients (CC/CC versus CC/non-CC) was analyzed. Results:Eighty-seven HIV/HCV genotype 1 co-infected patients were included in the study. Patients carrying the LDLr-CC or IL28B-CC genotypes showed greater HCV viral decline than those with IL28B non-CC or LDLr non-CC genotypes at every time-point analyzed. CC/CC patients had higher rapid virological response (RVR) rates than CC/non-CC patients (41.2 versus 13.3%; P < 0.001). Moreover, at all time points, the CC/CC pattern was associated with greater HCV viral decline than the CC/non-CC genotype (week 1: 1.18 ± 0.51 versus 0.31 ± 0.29, P = 0.041; week 2: 1.55 ± 0.81 versus 0.93 ± 0.73, P = 0.032; week 4: 2.23 ± 1.1 versus 1.5 ± 0.94, P = 0.039). Conclusion:The LDLr genotype impacts on viral kinetics during the first days of starting treatment with PEG-IFN/RBV in HIV/HCV genotype 1 co-infected patients, and modifies the impact of IL28B on HCV viral decay.

Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy.

Background and Aims Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. Methods In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. Results Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. Conclusion The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable.

Changes in liver steatosis evaluated by transient elastography with the controlled attenuation parameter in HIV‐infected patients

There are scant data on the progression of hepatic steatosis (HS) in HIV infection. We therefore evaluated changes in HS over time in HIV‐infected patients using the controlled attenuation parameter (CAP).

Association of low-density lipoprotein receptor genotypes with hepatitis C viral load

Several data suggest that low-density lipoprotein receptor (LDLR) is a co-receptor for hepatitis C virus (HCV). Soluble LDLR can inhibit HCV infectivity; greater plasma low-density lipoprotein levels are associated with treatment success; LDLR genotypes have a synergistic impact on the likelihood of achieving SVR with Peg-IFN plus RBV, as well as on viral kinetics after starting treatment. The objective of this study was to assess the impact of genetic polymorphisms in genes related to cholesterol synthesis and transport pathways on pre-treatment plasma HCV viral load (VL). A total of 442 patients infected with HCV and treatment naive were prospectively recruited. One hundred forty-four SNPs located in 40 genes from the cholesterol synthesis/transport and IL28B were genotyped and analyzed for genetic association with pre-treatment plasma HCV VL. SNPs rs1433099 and rs2569540 of LDLR showed association with plasma HCV VL (P=4 × 10−4 and P=2 × 10−3) in patients infected with genotypes 1 and 4. A haplotype including the last three exons of LDLR showed association with the cutoff level of 600 000 IU ml−1 VL for genotypes 1 and 4 (OR=0.27; P=8 × 10−6), as well as a quantitative VL (mean±s.d.: 6.19±0.9 vs CC+CG 5.58±1.1 logIU ml−1, P=8 × 10−5). LDLR genotypes are a major genetic factor influencing HCV VL in patients infected with genotypes 1 and 4.