Hepatitis: Force L

Almeda J, Casabona J, Allepuz A, García-Alcaide F, del Romero J, Tural C, Colm J, Bolao F, Campins M, Domínguez A, Force L, Giménez A, Guerra-Romero L, Anonymous00243. · Centre de Estudis Espidemiològics sobre la Sida a Catalunya. Hospital Universitari Germans Trias i Pujol. Badalona. España. · Enferm Infecc Microbiol Clin. · Pubmed #12372236 links to  free full text

Abstract: Evidence is lacking on the possible efficacy and effectiveness of non-occupational postexposure prophylaxis (PEP). However, because of its biological plausibility, the use of antiretroviral (ARV) drugs to prevent the development of infection in certain cases of accidental or sporadic exposure has begun to be considered as common clinical practice. Previous studies performed in Spain have demonstrated both the demand and the prescription of ARV as PEP and especially the diversity and inconsistency in the criteria used. In this context, in April of 2000 the Centre for Epidemiological Studies on AIDS of Catalonia (CEESCAT) (Department of Health and Social Security of the Autonomous Government of Catalonia), in collaboration with the National AIDS Plan and the AIDS Study Group (GESIDA), promoted the creation of a working group for the drafting of recommendations for PEP against HIV outside the occupational health context. The recommendations have been made bearing in mind the exceptional character of the exposure, the time elapsed since exposure, as well as evaluation of the risk of infection according to the type of exposure and the information available on the source of infection. In addition, the recommendations include the immediate measures necessary, as well as the preventive measures and clinical follow-up required both for HIV and for other infectious agents. All PEP regimens should be started within 72 hours of exposure and appropriate daily doses of two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI), or two NRTIs and a non-nucleoside reverse transcriptase inhibitor (NNRTIs), should be administered for four weeks, bearing in mind the pharmacological and clinical situation of the source person. These recommendations should be updated periodically.

Solà R, Galeras JA, Montoliu S, Tural C, Force L, Torra S, Montull S, Castro ER, Coll S, Fuster D, Barrufet P, Sirera G, Giménez MD, Clotet B, Planas R. · Liver Section, Hospital del Mar, Institut Municipal d'Investigació Médica, Universitat Autònoma de Barcelona, 08003 Barcelona, Spain. · AIDS Res Hum Retroviruses. · Pubmed #16706615 No free full text.

Abstract: The degree of adherence to anti-hepatitis C virus (HCV) therapy among HIV/HCV-coinfected patients is not known. A prospective cohort study was performed in two groups of patients: 79 HIV/HCV-coinfected patients (group 1) and 78-HCV-monoinfected patients (group 2). Patients were treated with interferon alpha-2a (3 million international units [MIU], three times per week) plus ribavirin (1000-1200 mg/day) for 48 weeks. Adherence to therapy was defined as having received +/-80% of both drug dosages for +/-80% of the expected duration of therapy. The degree of adherence to treatment was similar for patients with or without HIV coinfection (72.2 versus 80.8%). The overall sustained virological response (SVR) in patients with adherence to therapy was 41.7% as compared with only 8.1% (p = 0.0001) in patients without adherence. The difference in SVR rate according to adherence to treatment was also evident in patients of group 1 (29.8% versus 9.1%; p = 0.05) as well as in those of group 2 (52.4 versus 6.7%; p = 0.001). Adherence to anti-HCV therapy, which can be similar in mono- and coinfected patients, enhances the likelihood of achieving an increase in SVR rate. In addition to improved adherence, in coinfected patients more aggressive therapeutic strategies may be necessary to achieve SVR.

Fuster D, Huertas JA, Gómez G, Solà R, González García J, Vilaró J, Pedrol E, Force L, Tor J, Sirera G, Videla S, Planas R, Clotet B, Tural C, Anonymous00181. · HIV Clinical Unit/Fundació de la Lluita contra la SIDA/Internal Medicine Service and Hepatology Unit, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. · Antivir Ther. · Pubmed #16312180 No free full text.

Abstract: OBJECTIVE: To assess the baseline factors associated with haematological toxicity that lead to ribavirin or pegylated interferon (peginterferon) dosage reductions in hepatitis C and human immunodeficiency virus (HCV/HIV)-coinfected patients. DESIGN: Multicentre, prospective, observational study. Setting: Eleven hospitals in Spain during the period 2002-2003. SUBJECTS AND METHODS: One-hundred and forty-two HIV/HCV-coinfected patients received peginterferon-alpha2a plus ribavirin. Baseline characteristics and haematological parameters were recorded at baseline, week 4, 8, 12, 24 and 48. Cox's regression model was used to study the factors associated with the appearance of a haemoglobin level below 10g/dl (haemoglobin-endpoint), a neutrophil count below 750/mm(3) (neutrophil-endpoint) and a platelet count below 50,000/mm(3) (platelet-endpoint). RESULTS: Nineteen patients (13.4%) reached the haemoglobin-endpoint, 22.5% the neutrophil-endpoint and 7% the platelet-endpoint. Mean time of follow-up was 8 months (+/-3.5). A baseline haemoglobin level below 14g/dl [hazard ratio (HR): 3.65; 95% confidence interval (CI): 1.46-9.06] and treatment with zidovudine (HR: 3.25; 95% CI: 1.31-8.11) were the independent factors associated with the appearance of the haemoglobin-endpoint. A baseline neutrophil below 2050/mm(3) (HR: 3.59; 95% CI: 1.77-7.28) and baseline weight <60 kg (HR: 2.21; 95% Cl: 1.04-4.56) were independently associated with the appearance of the neutrophil-endpoint. Baseline platelet count (x1000/mm(3) decrease) (HR: 1.074; 95% CI: 1.04-1.11) was independently associated with the appearance of the platelet-endpoint. CONCLUSIONS: Baseline factors allow the identification of a subset of HIV/HCV-coinfected patients who are prone to experience haematological toxicity during HCV antiviral therapy.

Podzamczer D, Olmo M, Sanz J, Boix V, Negredo E, Knobel H, Domingo P, Pineda JA, Vilades C, Quero JH, Force L, Lahoz JG, Muñoz P, Llibre JM, Mariño A, Ortega E, Dalmau D, Gatell JM, Antón E, Sola J, Galindo MJ, Pedrol E, Sanz J, Lima JT, Flores J, Anonymous00075. · Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain. · J Acquir Immune Defic Syndr. · Pubmed #19214120 No free full text.

Abstract: BACKGROUND: The strategy of switching nevirapine (NVP) twice daily to once daily was evaluated. METHODS: Forty-eight-week randomized, open, multicenter trial. Stable HIV-infected patients on NVP twice daily for >12-18 weeks with alanine aminotransferase (ALT) <2.5, the upper normal limit were randomized to continue their regimen or switch to NVP 400 mg once daily. Primary end point was the proportion of ALT/aspartate transaminase (AST) > or =grade 3. RESULTS: Two hundred eighty-nine patients were included, mean CD4 620 cells per microliter. Noninferiority was demonstrated in the per protocol analysis, with 97.9% (once daily) and 99.3% (twice daily) of patients event free (difference, 1.4%; 95% confidence interval, -1.95% to 5.4%), whereas 81.8% vs. 93.8% were event free by intent-to-treat switch = toxicity analysis (difference, 12%; 95% confidence interval, 4.6% to 19.4%). Only 4 patients (3 once daily, 1 twice daily) had NVP-related grade 3/4 ALT/AST increases, but in 2 of them (once daily), transaminases decreased despite continuation with NVP. Two other once daily patients presented grade 3/4 ALT/AST increase due to well-documented acute hepatitis A virus or hepatitis C virus infection. Grade 2 ALT/AST increases occurred in 11.2% (once daily) vs. 10.3% (twice daily) of patients (P = 0.80). A larger number of once daily patients were lost to follow-up/violated protocol (15% vs. 5%). CONCLUSIONS: In patients on standard twice daily NVP-containing regimens for at least 12-18 weeks, per protocol analysis showed that switching to once daily NVP was not inferior to continued twice daily NVP in terms of the predefined noninferiority margin of 10% for hepatotoxicity.

Jaén A, Esteve A, Miró JM, Tural C, Montoliu A, Ferrer E, Riera M, Segura F, Force L, Sued O, Vilaró J, Garcia I, Masabeu A, Altès J, Coltet B, Podzamczer D, Murillas J, Navarro G, Gatell JM, Casabona J, Anonymous00385. · Centre d'Estudis Epidemiològics sobre ITS/VIH/SIDA de Catalunya, Badolona, Spain (CEEISCAT, coordinating center). · J Acquir Immune Defic Syndr. · Pubmed #18297762 No free full text.

Abstract: OBJECTIVE: We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. METHODS: We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. RESULTS: Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. CONCLUSIONS: Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.

Fuster D, Planas R, Gonzalez J, Force L, Cervantes M, Vilaró J, Roget M, García I, Pedrol E, Tor J, Ballesteros AL, Salas A, Sirera G, Videla S, Clotet B, Tural C. · HIV Clinical Unit/ Fundació de Lluita contra la SIDA/ Internal Medicine Service University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain. · Antivir Ther. · Pubmed #16856621 No free full text.

Abstract: OBJECTIVE: To assess the efficacy and safety of an extended treatment period in HIV/hepatitis C virus (HCV)-coinfected patients without early virological response (EVR). METHODS: Patients received pegylated interferon (peg-INF)-alpha2a 180 microg/week plus ribavirin 800 mg/d for 12 weeks. Patients achieving EVR at week 12 continued under therapy for an additional 12 or 36 weeks depending on genotype. Patients without EVR were randomized to complete the standard treatment or treatment lasting 72 weeks (extension arm). RESULTS: One hundred and ten patients were included (mean age 38.7 years, mean weight 68 kg, 74% males, 74% on highly active antiretroviral therapy, mean CD4+ T-cell count 564 cells/mm3). Fifty-one patients harboured genotype 1, 44 genotype 2/3, and 15 genotype 4. Fifty-three had an HCV load >800,000 IU/ml. Premature interruptions occurred in 32.7%. EVR was achieved in 63.6% (51% in genotype 1, 88.6% in genotype 2/3, 33.3% in genotype 4). End-of-treatment response was 52.7% (47.2% in genotype 1, 68.2% in genotype 2/3, 26.7% in genotype 4). Sustained virological response (SVR) was achieved in 41.8% (37.3% in genotype 1, 54.6% in genotype 2/3, 20% in genotype 4). Only one patient allocated to the extended arm achieved SVR. The rate of drop-outs in the extension arm was 68%. The negative predictive value of EVR was 97.5%. CONCLUSIONS: This study shows no benefit of extending therapy in patients without EVR at week 12. Measures to improve adherence to HCV antiviral therapy should be considered when new approaches based on extended periods of treatment are investigated.