Iñaki Pérez

Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

Eighty‐four HCV/HIV‐coinfected and 252‐matched HCV‐monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty‐six (43%) HCV/HIV‐coinfected and 75 (30%) HCV‐monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42–64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420–3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV‐coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32–6.76), donor risk index (HR, 9.48; 95% CI, 2.75–32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03–0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV‐infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5‐year prognosis (69%[95% CI, 54–80]) to that of HCV‐monoinfected recipients. In conclusion, 5‐year survival in HCV/HIV‐coinfected liver recipients was lower than in HCV‐monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.

Randomized trial comparing pegylated interferon α‐2b versus pegylated interferon α‐2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients

Although two pegylated interferons (Peg‐IFN) are available to treat chronic hepatitis C virus (HCV) infection, no head‐to‐head comparative studies have been published. We aim to compare the efficacy and safety of PEG IFN alfa‐2b (PEG 2b) versus PEG IFN alfa‐2a (PEG 2a), plus ribavirin (RBV). A prospective, randomized, multi‐center, open‐label clinical trial including 182 human immunodeficiency virus (HIV)–hepatitis C virus (HCV) patients naïve for HCV therapy was performed. Patients were assigned to PEG 2b (80‐150 μg/week; n = 96) or PEG 2a (180 μg/week; n = 86), plus RBV (800‐1200 mg/day) for 48 weeks. The primary endpoint was sustained virological response (SVR: negative HCV‐RNA 24 weeks after completion of treatment). At baseline, both groups were well balanced: 73% male; 63% HCV genotype 1 through 4; 29% had fibrosis index of 3 or greater. The overall SVR was 44% (42% PEG 2b versus 46% PEG 2a, P = 0.65). Among genotypes 1 through 4, SVRs were 28% versus 32% (P = 0.67) and 62% versus 71% (P = 0.6) in genotypes 2 through 3 for PEG 2b and PEG 2a, respectively. Early virological response (EVR; ≥2 log reduction from baseline or negative HCV‐RNA at week 12) was 70% in the PEG 2b group and 80% in the PEG 2a group (P = 0.13), reaching a positive predictive value of SVR of 64% and a negative predictive value of 100% in both arms. Side effects were present in 96% of patients but led to treatment discontinuation in 10% of patients (8% on PEG 2b and 13% on PEG 2a, P = 0.47). Conclusion: In patients with HIV, HCV therapy with PEG 2b or PEG 2a plus RBV had no significant differences in efficacy and safety. (HEPATOLOGY 2009;49:22‐31.)

Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02).

BACKGROUND To investigate the safety and immunogenicity of a modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B), a phase-I, doubled-blind placebo-controlled trial was performed. METHODS 30 HIV-uninfected volunteers at low risk of HIV-1 infection were randomly allocated to receive 3 intramuscular injections (1×10(8)pfu/dose) of MVA-B (n=24) or placebo (n=6) at weeks 0, 4 and 16. All volunteers were followed 48 weeks. Primary end-points were adverse events and immunogenicity. RESULTS A total of 169 adverse events were reported, 164 of grade 1-2, and 5 of grade 3 (none related to vaccination). Overall 75% of the volunteers showed positive ELISPOT responses at any time point. The magnitude (median) of the total responses induced was 288SFC/10(6)PBMC at week 18. Antibody responses against Env were observed in 95% and 72% of vaccinees at week 18 and 48, respectively. HIV-1 neutralizing antibodies were detected in 33% of volunteers. CONCLUSIONS MVA-B was safe, well tolerated and elicited strong and durable T-cell and antibody responses in 75% and 95% of volunteers, respectively. These data support further exploration of MVA-B as an HIV-1 vaccine candidate. Clinical Trials.gov identifier: NCT00679497.

Epidemiology and outcome of infections in human immunodeficiency virus/hepatitis C virus-coinfected liver transplant recipients: a FIPSE/GESIDA prospective cohort study.

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)–infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)–coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV‐coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow‐up was 2.6 years (interquartile range = 1.25‐3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty‐eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty‐three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty‐six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3‐fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5‐5.8]. Independent factors for severe infections included a pretransplant Model for End‐Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70‐7.1), a history of AIDS‐defining events before transplantation (HR = 4.0, 95% CI = 1.9‐8.6), and non–tacrolimus‐based immunosuppression (HR = 2.5, 95% CI = 1.3‐4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV‐coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non–tacrolimus‐based immunosuppression. Liver Transpl 18:70–82, 2012.

Differences between HIV‐infected and uninfected adults in the contributions of smoking, diabetes and hypertension to acute coronary syndrome: two parallel case–control studies

The aim of the study was to assess the separate contributions of smoking, diabetes and hypertension to acute coronary syndrome (ACS) in HIV‐infected adults relative to uninfected adults.

HIV-1 Infection in Subjects Older than 70: A Multicenter Cross-Sectional Assessment in Catalonia, Spain

We designed a multicenter cross-sectional study to describe the epidemiological characteristics of the HIV-1-infected population aged 70 years or more in our setting. 179 individuals from eight university hospitals in Barcelona, Spain, were included, representing 1.5% of HIV-1 infected subjects followed during 2008. Most subjects were male (76%) and had acquired HIV infection through sexual intercourse (87%); 69% had been diagnosed with HIV-1 after their sixties. The CD4 cell counts at HIV-1 diagnosis were < 200 cells/mm(3) in 52% of individuals, whereas this was only seen in 34% of subjects from a published cohort including younger HIV- infected adults from the same setting [1]. Most of our patients were on HAART, had undetectable HIV-1 viremia and the most recent median CD4 cell counts were >or= 350 cells/mm(3). 154 subjects had at least one comorbid condition, including dyslipidemia (54%), hypertension (36%), hyperglycemia or diabetes (30%), cardiovascular disease (23%), chronic renal failure (18%), history of neoplasia (17%) and cognitive impairment (11%). Lipodystrophy was reported in 58% of individuals. Rates of hypercholesterolemia, diabetes and cancer were higher than those reported in unselected local population (28%, 17% and 7%, respectively). The study participants were taking an average of 2.97 drugs (range 1-10) other than antiretrovirals. In conclusion, the elder population infected with HIV-1 is likely being diagnosed late and at lower CD4+ counts and is frequently affected by comorbidities and co-medication. Based on our findings, we suggest some recommendations regarding the management of this growing population.

Dual therapy with etravirine plus raltegravir for virologically suppressed HIV-infected patients: a pilot study

BACKGROUND Clinical use of protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) may be hampered by toxicity, interactions or resistance issues. Simple and effective antiretroviral regimens avoiding both drug classes may be needed for selected patients. METHODS This was a prospective cohort study. Virologically suppressed patients on PI or NRTI regimens, with problems of tolerability, safety concerns due to comorbidities or risk of drug interactions for both PIs and NRTIs, were given the opportunity to switch their regimen to etravirine plus raltegravir. Patients were required not to have prior virological failure to raltegravir and if there was prior non-nucleoside reverse transcriptase inhibitor (NNRTI) virological failure, only patients in whom efficacy of etravirine could be anticipated through the Stanford Drug Resistance Database were included. Follow-up was scheduled for at least 48 weeks, unless the patient was lost to follow-up or discontinued therapy. RESULTS Twenty-five patients were included. Their median age was 54 years; they had a median of 16 years on antiretroviral therapy and a median of nine previous regimens; 21 (84%) patients had previous virological failure; and 15 (60%) patients had a genotypic test that showed three or more NRTI mutations in 9 (36%), four or more PI mutations in 11 (44%) and at least one NNRTI mutation in 8 (32%) patients. At 48 weeks efficacy was 84% (95% CI 65.3%-93.6%) by intent-to-treat analysis and 91.3% (95% CI 73.2%-97.6%) by per-protocol analysis. One (4%) patient died, two (8%) discontinued due to intolerance and one (4%) experienced virological failure. The CD4/CD8 ratio and plasma lipids improved. CONCLUSIONS Dual therapy with etravirine plus raltegravir was well tolerated and maintained durable viral suppression in selected virologically suppressed patients for whom both PI and NRTI therapy was challenging.

Early lipid changes with atazanavir/ritonavir or darunavir/ritonavir.

Ritonavir‐boosted atazanavir and darunavir are protease inhibitors that are recommended for initial treatment of HIV infection because each has shown better lipid effects and overall tolerability than ritonavir‐boosted lopinavir. The extent to which lipid effects and overall tolerability differ between treatments with atazanavir and darunavir and whether atazanavir‐induced hyperbilirubinaemia may result in more favourable metabolic effects are issues that remain to be resolved.

Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: A prospective cohort study

BACKGROUND & AIMS The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients. METHODS This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. RESULTS Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p=0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. CONCLUSIONS The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly.

Brote epidémico de hepatitis aguda C en pacientes infectados por el virus de la inmunodeficiencia humana

BACKGROUND Recent studies suggest an increased incidence of acute infection with hepatitisC virus (AHC) in men who have sex with men (MSM) co-infected with HIV. Early treatment with interferon-alpha, alone or in combination with ribavirin, significantly reduces the risk of chronic evolution. METHODS This retrospective study includes all HIV patients with AHC in our centre from 2003 to March 2013. AHC was defined by seroconversion of HCV antibodies and detection of serum HCV RNA. RESULTS 93 episodes of AHC were diagnosed in 89 patients. All but three were MSM with a history of unprotected sex. Thirty-seven (40%) patients had other associated sexually transmitted disease. The 29% (27) had any symptoms suggestive of AHC. HCV genotype 4 was the most common (41%), followed by genotype1. Seventy patients started treatment with interferon-alfa and weight-adjusted ribavirin. Currently 46 have completed treatment and follow-up, reaching 26 of them (56.5%) sustained viral response. CONCLUSIONS The incidence of AHC in HIV MSM patients from our centre has increased exponentially in recent years; sexual transmission remains the main route of infection. Early treatment with interferon-alpha and ribavirin achieved a moderate response in these patients.