Hepatitis: Miró JM

Miró JM, Torre-Cisnero J, Moreno A, Tuset M, Quereda C, Laguno M, Vidal E, Rivero A, Gonzalez J, Lumbreras C, Iribarren JA, Fortún J, Rimola A, Rafecas A, Barril G, Crespo M, Colom J, Vilardell J, Salvador JA, Polo R, Garrido G, Chamorro L, Miranda B. · AIDS Study Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). · Enferm Infecc Microbiol Clin. · Pubmed #15970168 links to  free full text

Abstract: Solid organ transplant may be the only therapeutic alternative in some HIV-infected patients. Experience in North America and Europe during the last five years shows that survival at three years after an organ transplant is similar to that observed in HIV-negative patients. The criteria agreed upon to select HIV patients for transplant are: no opportunistic infections (except tuberculosis, oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4 lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver transplant) and an HIV viral load which is undetectable or suppressible with antiretroviral therapy. Another criterion is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection and the management of relapse of HCV infection, which is one of the main causes of post-liver transplant mortality. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. The English version of the manuscript is available at http://www.gesidaseimc.com.

Rubio R, Berenguer J, Miró JM, Antela A, Iribarren JA, González J, Guerra L, Moreno S, Arrizabalaga J, Clotet B, Gatell JM, Laguna F, Martínez E, Parras F, Santamaría JM, Tuset M, Viciana P. · Hospital 12 Octubre, Madrid, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #12084354 links to  free full text

Abstract: OBJECTIVE: To provide an update of recommendation on antiretroviral treatment (ART) in HIV-infected adults.Methods. These recommendations have been agreed by consensus by a committee of the spanish AIDS Study Group (GESIDA) and the National AIDS Plan. To do so, advances in the physiopathology of AIDS and the results on efficacy and safety in clinical trials, cohort and pharmacokinetics studies published in biomedical journals or presented at congresses in the last few years have been reviewed. Three levels of evidence have been defined according to the data source: randomized studies (level A), case-control or cohort studies (level B) and expert opinion (level C). Whether to recommend, consider, or not to recommend ART has been established for each situation. RESULTS: Currently, ART with combinations of at least three drugs constitutes the treatment of choice in chronic HIV infection. In patients with symptomatic HIV infection, initiation of ART is recommended. In asymptomatic patients initiation of ART should be based on the CD41/mL lymphocyte count and on the plasma viral load (PVL): a) in patients with CD41 lymphocytes < 200 cells/mL, initiation of ART is recommended; b) in patients with CD41 lymphocytes between 200 and 300 cells/mL, initiation of ART should, in most cases, be recommended; however, it could be delayed when the CD41 lymphocyte count remains close to 350 cells/mL and the PVL is low, and c) in patients with CD41 lymphocytes > 350 cells/mL, initiation of ART can be delayed. The aim of ART is to achieve an undetectable PVL. Adherence to ART plays a role in the durability of the antiviral response. Because of the development of cross-resistance, the therapeutic options in treatment failure are limited. In these cases, genotypic analysis is useful. Toxicity limits ART. The criteria for ART in acute infection, pregnancy and postexposure prophylaxis and in the management of coinfection with HIV and hepatitis C and B virus are controversial. CONCLUSIONS: The current approach to initiating ART is more conservative than in previous recommendations. In asymptomatic patients, the CD41 lymphocyte count is the most important reference factor for initiating ART. Because of the considerable number of drugs available, more sensitive monitoring methods (PVL) and the possibility of determining resistance, therapeutic strategies have become much more individualized.

Torre-Cisneros J, Miró JM. · No affiliation provided · Med Clin (Barc). · Pubmed #10472610 No free full text.

This publication has no abstract.

Miró JM, Laguno M, Moreno A, Rimola A, Anonymous00233. · Infectious Diseases Service, Hospital Clinic-IDIBAPS, Villarroel, 08036 Barcelona, Spain. · J Hepatol. · Pubmed #16352366 No free full text.

Abstract: Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count > 100 cells/mm(3), and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern.

Trullás JC, Miró JM, Barril G, Ros S, Burgos FJ, Moreno A, Mazuecos A, Alvarez-Vijande R, Oppenheimer F, Carmen Sánchez M, Blanco JL, Tuset M, Torre-Cisneros J, Polo R, González J. · Hospital Clínic-IDIBAPS, Universidad de Barcelona, Barcelona, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15970170 links to  free full text

Abstract: The prevalence of human immunodeficience virus (HIV) infection among patients under renal replacement therapy varies, with estimates of 1% for Europe and 1.5% for the United States. Survival in HIV infected individuals receiving renal replacement therapy has improved since the introduction of high activity antiretroviral therapy (HAART). Current experience in renal transplantation in HIV-infected patients in the United States indicates that the three-year survival rate is similar to that of HIV-negative transplant recipients, with virological and immunological control of the infection by HAART and no increase in the number of opportunistic infections or tumors. The criteria for selecting renal transplantation candidates in this population are the following: no aids-defining events, CD4 cells > 200 cells/.l and undetectable viral load under HAART. In Spain, where most of these patients are former drug abusers, a two-year period of abstinence from cocaine and heroine abuse is also required, although patients can be participating in the methadone program. The main problems in the post-transplantation period have been interactions between HAART and immunosuppressive drugs, management of hepatitis C virus (HCV) coinfection and the high rate of acute rejection. To date, seven such renal transplantations have been performed in Spain, with favorable patient and graft survival and no progression to aids.

Laguno M, Sánchez-Tapias JM, Murillas J, Forns X, Blanco JL, Martínez E, Larrousse M, León A, Loncá M, Milinkovic A, Miró JM, García F, Gatell JM, Mallolas J. · Servicio de Enfermedades Infecciosas, Hospital Clínic-Universitari de Barcelona-IDIBAPS, Universitat de Barcelona, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15701331 links to  free full text

Abstract: The chronic infection by the hepatits C virus represents a serious sanitary problem affecting 1-3% of the world-wide population. It is transmitted by sexual route, vertical route and mainly after blood exposure by percutanea route. While HIV shares similar routes of transmission, the co-infection HCV-HIV is very frequent and the chronic hepatopathy and complications associated with its clinical course are an important cause of morbi-mortality in this population. The gold standard of the treatment for the HCV, has been the interferon and later the combination therapy of interferon plus ribavirine. Currently, the combination of ribavirine and a new pegilated formulation of the interferon has become the standard in the treatment reaching rates of sustained viral response around 40-80%.

Miró JM, Montejo M, Rufí G, Bárcena R, Vargas V, Rimola A, Bañares R, Valdivieso A, Fabregat J, Vicente E, Margarit C, Moreno A, Miralles P, Aguirrebengoa K, Xiol FX, Fortún J, Pahissa A, Laguno M, Salcedo M, Cisneros JM, Quereda C, Tuset M, Castón JJ, Torre-Cisneros J, Anonymous00290. · Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15511394 links to  free full text

Abstract: According to current estimates, there are 60,000 to 80,000 HIV and HCV coinfected individuals in Spain, and 5,000 to 10,000 HIV and HBV coinfected individuals. Among these patients, 10% to 15% have liver cirrhosis. Thus, end-stage liver disease is one of the major causes of death in our country. Liver transplantation is the only therapeutic option for these patients. Accumulated experience in North America and Europe in the last five years indicates that three-year survival in HIV-positive liver transplant recipients is similar to that of HIV-negative recipients. The selection criteria for HIV transplant candidates includes the following: no history of opportunistic infections, CD4 lymphocyte count higher than 100 cells/mm3, and HIV viral load suppressible with antiretroviral treatment. In Spain, where the majority of patients are former drug abusers, complete abstinence from heroin or cocaine use during two years is also required, with the possibility of the patient being in a methadone program. To date 26 hepatic transplants have been performed in the same number of patients, with only two deaths (7%) after a median follow-up of eight months (1-28). The main problems in the post-transplantation period in all the series has been recurrent HCV infection, which is the principle cause of post-transplantation mortality, and pharmacokinetic and pharmacodynamic interactions between the antiretroviral and immunosuppressive agents. There is little experience with pegylated interferon and ribavirin treatment in this population.

Soriano V, Miró JM, García-Samaniego J, Torre-Cisneros J, Núñez M, del Romero J, Martín-Carbonero L, Castilla J, Iribarren JA, Quereda C, Santín M, González J, Arribas JR, Santos I, Hernández-Quero J, Ortega E, Asensi V, del Pozo MA, Berenguer J, Tural C, Clotet B, Leal M, Mallolas J, Sánchez-Tapias JM, Moreno S, Gatell JM, Téllez MJ, Rubio R, Ledesma E, Domingo P, Barreiro P, Pedreira J, Romero M, González-Lahoz J, Lissen E. · Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · J Viral Hepat. · Pubmed #14738553 No free full text.

Abstract: Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Tuset M, Martín-Conde MT, Miró JM, Del Cacho E, Alberdi A, Codina C, Ribas J. · Servicio de Farmacia. IDIBAPS-Hospital Clínic i Provincial. Barcelona. España. · Enferm Infecc Microbiol Clin. · Pubmed #14525709 links to  free full text

Abstract: This article summarizes the principal characteristics of the drugs used to treat viral infections, with the exception of human immunodeficiency virus infection. It includes antiviral agents active against herpes virus, cytomegalovirus, hepatitis B and C virus, and respiratory viruses, such as influenza and respiratory syncytial virus. Dosage according to the indication, dose adjustment in the case of renal or hepatic insufficiency, significant pharmacokinetic characteristics, and the main adverse effects and interactions are described.

García-Samaniego J, Soriano V, Miró JM, Romero JD, Bruguera M, Castilla J, Esteban JI, Gonźlez J, Lissen E, Moreno A, Moreno S, Moreno-Otero R, Ortega E, Quereda C, Rodríguez M, Sánchez-Tapias JM, Anonymous00176. · Hepatology, Hospital Carlos III, Instituto de Salud Carlos III, Madrid, Spain. · HIV Clin Trials. · Pubmed #11976988 links to  free full text

Abstract: Co-infection by human immunodeficiency virus and hepatitis B and C viruses is quite common because they share similar routes of transmission. The introduction of highly active antiretroviral therapy has significantly improved the life expectancy of HIV-infected patients in the last few years. However, chronic viral hepatitis represents an emerging cause of morbidity and mortality in this population, either as a result of end-stage liver disease or as a consequence of hepatotoxicity induced by antiretroviral drugs. The main goal of the Consensus Conference was to establish specific recommendations for the management of chronic viral hepatitis B and C in HIV-infected patients. The role of orthotopic liver transplantation for co-infected individuals with end-stage liver disease was also assessed.

Trullàs JC, Barril G, Cofan F, Moreno A, Cases A, Fernandez-Lucas M, Martinez-Ara J, Ceballos M, Garcia-de-Diego J, Muñiz ML, Molina J, Martínez-Castelao A, González-Garcia J, Miró JM, Anonymous00029. · Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain. · AIDS Res Hum Retroviruses. · Pubmed #18834322 No free full text.

Abstract: End-stage renal diseases (ESRD) are becoming more frequent in HIV-infected patients. In Europe there is little information about HIV-infected patients on dialysis. A cross-sectional multicenter survey in 328 Spanish dialysis units was conducted in 2006. Information from 14,876 patients in dialysis was obtained (81.6% of the Spanish dialysis population). Eighty-one were HIV infected (0.54%; 95% CI, 0.43-0.67), 60 were on hemodialysis, and 21 were on peritoneal dialysis. The mean (range) age was 45 (28-73) years. Seventy-two percent were men and 33% were former drug users. The mean (range) time of HIV infection was 11 (1-27) years and time on dialysis was 4.6 (0.4-25) years. ESRD was due to glomerulonephritis (36%) and diabetes (15%). HIV-associated nephropathy was not reported. Eighty-five percent were on HAART, 76.5% had a CD4 T cell count above 200 cells, and 73% had undetectable viral load. Thirty-nine percent of patients met criteria for inclusion on the renal transplant (RT) waiting list but only 12% were included. Sixty-one percent had HCV coinfection. HCV-coinfected patients had a longer history of HIV, more previous AIDS events, parenteral transmission as the most common risk factor for acquiring HIV infection, and less access to the RT waiting list (p < 0.05). The prevalence of HIV infection in Spanish dialysis units in 2006 was 0.54% HCV coinfection was very frequent (61%) and the percentage of patients included on the Spanish RT waiting list was low (12%).

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.

Larrousse M, Laguno M, Segarra M, De Lazzari E, Martinez E, Blanco JL, León A, Deulofeu R, Miquel R, Milinkovic A, Lonca M, Miró JM, Biglia A, Murillas J, Gatell JM, Mallolas J. · Infectious Diseases Unit, Hospital Clínic Universitari de Barcelona-IDIBAPS, University of Barcelona, Spain. · J Acquir Immune Defic Syndr. · Pubmed #18172937 No free full text.

Abstract: BACKGROUND: Several serum markers reflecting extracellular matrix status have been correlated with liver fibrosis in non-HIV-infected patients with chronic hepatitis C infection. These indexes have been less examined in HIV/HCV-coinfected individuals. OBJECTIVE: We aimed to evaluate the predictive value of serum markers for liver fibrosis in HIV-infected patients with chronic hepatitis C virus (HVC). METHODS: Serum levels of metalloproteinases 1 and 2 (MMP-1 and -2), tissue inhibitors of matrix metalloproteinases (TIMP-1), procollagen type III N-terminal peptide (PIIINP), and hyaluronic acid (HA) were measured in HIV-infected patients with chronic hepatitis C at the time of obtaining a liver biopsy and before the consideration of anti-hepatitis C therapy. RESULTS: One hundred and nineteen consecutive HIV-HVC coinfected patients were included. TIMP-1 (r = 0.6; P < 0.001), TIMP-1/MMP-1 ratio (r = 0.5; P < 0.001), TIMP-1/MMP-2 ratio (r = 0.3; P < 0.001), MMP-2 (r = 0.2; P = 0.044), PIIINP (r = 0.4; P < 0.001), and HA (r = 0.5; P < 0.001) were positively and significantly correlated with the fibrosis stage. In the multivariate analysis, TIMP-1 (odds ratio [OR] = 1.004, 95% confidence interval [CI]: 1.002 to 1.006, P = 0.001) and HA >95 microg/dL (OR = 6.041, 95% CI: 1.184 to 30.816, P = 0.031) were independently associated with liver fibrosis. The area under the curve of score to discriminate mild (F0-F1) from significant (F2-F4) fibrosis in the received-operating analysis using the variables TIMP-1 and HA was 0.84, with a sensitivity of 72.9% and a specificity of 83.1%. CONCLUSION: TIMP-1 and HA were quite sensitive and specific for predicting the degree of liver fibrosis in HIV-infected patients with chronic hepatitis C. These parameters may become a noninvasive alternative to liver biopsy when the degree of liver fibrosis needs to be estimated.

Soriano A, Lozano F, Oliva H, García F, Nomdedéu M, De Lazzari E, Rodríguez C, Barrasa A, Lorenzo JI, Del Romero J, Plana M, Miró JM, Gatell JM, Vives J, Gallart T. · Service of Infectious Diseases and AIDS Unit, Hospital Clínic de Barcelona, Villarroel, 170, 08036, Barcelona, Spain. · Immunogenetics. · Pubmed #16189667 No free full text.

Abstract: Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor alpha chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV+ long-term nonprogressors (LTNP), 36 HIV+ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus+), and 97 healthy controls (HC), all Caucasians and lacking CCR5Delta32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p = 0.005; relative risk ratio = 3.4, 95% confidence interval (CI) = 1.12-10.6, p = 0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV+ individuals (n = 64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p = 0.01; odds ratio (OR) = 2.14, 95% CI = 1.25-3.67, p = 0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR = 2.10, 95% CI = 1.03-4.21, p = 0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p = 0.043). Distributions of genotypes fitted Hardy-Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.

Barril G, Trullás JC, González-Parra E, Moreno A, Bergada E, Jofre R, Martínez-Ara J, de Sequera P, Oliver JA, Arrieta J, Miró JM. · Servicio de Nefrología, Hospital Universitario La Princesa, Madrid, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15970165 links to  free full text

Abstract: INTRODUCTION: Patients with HIV infection and end-stage renal disease (ESRD) have improved their survival in the last few years. HIV infection is not considered a contradiction for renal transplantation, but little experience exists in renal transplantation in HIV infected individuals. There is no information about the prevalence of HIV infection in Spanish patients under renal replacement therapies (RRT). METHODS: A survey was performed in Spanish dialysis units during 2004. The objective was to study the prevalence and characteristics of HIV infection in patients under RRT in Spain. We also aimed to know how many of them met the Spanish criteria to be included on the renal transplantation waiting list. RESULTS: HIV prevalence was 1.15% (95%CI 0.85-1.45) of 4,962 patients who were under RRT, mostly under hemodialysis and, less commonly, peritoneal dialysis. The most frequent risk factor for HIV infection was parenteral drug use (58%). The most common causes of ESRD were glomerulonephritis (44%). The median time under RRT was 46 months. Coinfections with hepatitis C (60%) and B (7%) were found. Thirty-four percent of patients had a history of aids-defining events. Eighty-six percent were under HAART. The median CD4 cell count was 333 cells/.l and the viral load was undetectable in 68%. Of 40 patients with a completed clinical questionnaire, 9 (22.5%) met the Spanish criteria for renal transplantation. CONCLUSION: HIV prevalence in patients under RRT in Spain is 1.15% (0.85%-1.45%) and 22.5% percent of these patients met the Spanish criteria to be included on a renal transplantation waiting list.

Laguno M, Milinkovic A, de Lazzari E, Murillas J, Martínez E, Blanco JL, Loncá M, Biglia A, Leon A, García M, Larrousse M, García F, Miró JM, Gatell JM, Mallolas J. · Infectious Diseases Unit, Hospital Clinic Barcelona, Barcelona, Spain. · Antivir Ther. · Pubmed #15918333 No free full text.

Abstract: BACKGROUND: Coinfection with hepatitis C virus (HCV) and HIV is not uncommon and therapies for both infections are currently available. A major drawback, however, could be a potentially higher risk for mitochondrial toxicity (MT), defined as the elevation of pancreatic enzymes or lactate levels due to the nucleoside analogue reverse transcriptase inhibitors contained in both therapies. METHODS: Prospective analyses of clinical and laboratory data, including plasma lactate levels and pancreatic enzymes, of 113 consecutive HIV/HCV-coinfected patients were assigned to receive ribavirin (RBV) plus interferon (IFN)-alpha. RESULTS: Fourteen patients (12%) showed increased levels of amylase/lipase and/or hyperlactataemia. No patient developed clinical pancreatitis. Four patients with hyperlactataemia had clinical symptoms of lactic acidosis and recovered uneventfully by 2 weeks after treatment withdrawal. The variables significantly associated with MT in the univariate analysis were: therapy with didanosine (ddl), ddl plus stavudine (d4T), previous history of diabetes and the baseline lactate level. However, ddl use was the only independent risk factor for MT identified in the multivariate analysis. MT was not associated with gender, age, alcohol consumption, type of IFN, degree of steatosis and fibrosis in liver biopsy, presence of lipodystrophy, CD4+ cell count, HCV or HIV viral load, mitochondrial DNA and COXII-expression in liver tissue, or antiretroviral therapy containing d4T or protease inhibitors. CONCLUSIONS: 12% of HIV/HCV-coinfected patients receiving IFN plus RBV concomitantly with highly active antiretroviral therapy developed laboratory markers of MT. Although most of cases were asymptomatic, our study suggests that concomitant use of RBV plus ddl should be avoided, and that routine monitoring of lactate and pancreatic enzymes may be recommended.

Laguno M, Blanch J, Murillas J, Blanco JL, León A, Lonca M, Larrousse M, Biglia A, Martinez E, García F, Miró JM, de Pablo J, Gatell JM, Mallolas J. · Infectious Diseases Unit, Hospital Clinic Universitari de Barcelona, Barcelona, Spain. · Antivir Ther. · Pubmed #15651749 No free full text.

Abstract: BACKGROUND: Interferon alpha (IFN-alpha) therapy for chronic hepatitis C (CHC) infection is commonly associated with neuropsychiatric side effects including depressive symptomatology. In this study, we evaluated the incidence and management of depressive symptoms during IFN-alpha therapy in HIV-infected patients with CHC. METHODS: HIV-infected patients with CHC who began IFN-alpha and ribavirin therapy during the recruitment period April 2001 to April 2003 were included in the study. Patients with a history of major depressive disorder were excluded. RESULTS: Of 113 co-infected patients who started IFN-alpha therapy during the recruitment period, 45 (40%) developed symptoms of depression (sadness, tiredness and apathy). Twenty of them (44%) were treated with citalopram, a selective serotonin re-uptake inhibitor, resulting in a significant improvement in their symptoms. Most of the patients (60%) showed depressive side effects in the first 3 months after initiation of IFN-alpha. In addition, during the study, three patients developed psychotic symptoms and one committed suicide. CONCLUSIONS: The incidence of depressive symptoms in patients with HIV/HCV co-infection treated with IFN-alpha is high. Most of the depressive symptoms were not severe and improved with antidepressant therapy, without reduction or cessation of IFN-alpha therapy. During the first weeks after initiating IFN-alpha therapy for HIV/HCV co-infection, close assessment of psychiatric symptoms is recommended. Early treatment of these side effects with antidepressants would help avoid early dropouts from interferon therapy.

Soriano A, Martínez C, García F, Plana M, Palou E, Lejeune M, Aróstegui JI, De Lazzari E, Rodriguez C, Barrasa A, Lorenzo JI, Alcamí J, del Romero J, Miró JM, Gatell JM, Gallart T. · Institut Clínic d'Infeccions i Immunologia, Hospital Clínic Universitari, Barcelona, Spain. · J Infect Dis. · Pubmed #12232832 No free full text.

Abstract: Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3'A polymorphism, and CXCR4(+) T lymphocytes in relation to resistance to human immunodeficiency virus (HIV)-1 infection and its progression were investigated in a study of HIV-positive patients, exposed but uninfected (EU) subjects, and healthy control subjects, all lacking CCR5 Delta 32 homozygosity. SDF1-3'A homozygosity was associated with low plasma SDF-1 levels in uninfected persons and was not related to long-term nonprogression. HIV-1 infection involved increased plasma SDF-1 levels, which were not attributable to any kind of chronic viral infection, because all EU hemophiliacs were hepatitis C virus-positive but had normal SDF-1 levels. High plasma SDF-1 levels and low CXCR4 expression on T lymphocytes was associated with long-term nonprogression, whereas in advancing disease expression of CXCR4 increased, accompanied by a decrease in plasma SDF-1 during the more advanced stages of HIV-1 infection. EU subjects with sexual exposure to HIV-1, but not EU hemophiliacs, showed an underpresentation of SDF1-3'A allele frequency, which was coupled with high plasma SDF-1 levels and low CXCR4 expression.