[Show abstract][Hide abstract] ABSTRACT: Etravirine has become an alternative in HIV/HCV coinfected patients because of safety and lack of interactions with anti-HCV drugs. The aim of this study was to establish the risk of liver toxicity in HIV/HCV coinfected patients receiving etravirine in the clinical setting, according to the degree of liver fibrosis and different accompanying drugs.
Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19574. · 4.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are few data of fibrosis development in chronic hepatitis B (CHB) patients classified as inactive carriers. The aim of this study is to determinate the prevalence of significant fibrosis and probable cirrhosis measured by FibroScan in real inactive CHB carriers and investigate the relationship with virological, epidemiological and metabolic factors.
Cross-sectional cohort study including CHB inactive carriers. Liver stiffness measurement was performed with transient elastography (FibroScan). Significant fibrosis (≥F2) was defined as stiffness >7.5 kPa, and probable cirrhosis as >11.8 kPa. Factors associated with significant fibrosis were explored with univariate and multivariate adjusted logistic regression analyses.
96 CHB inactive carriers were analyzed. Of them, 24 (25%) had significant fibrosis and 7 (7%) probable cirrhosis; mean stiffness was 6.2±2.3 kPa. Of them, 24% had metabolic syndrome, with higher FibroScan value than those without (8.4 kPa vs 5.5 kPa, p<0.001). Factors associated with significant fibrosis were (odds ratio, 95% confidence interval, p value): central obesity (7.1, 1.8-27.9, 0.005), elevated fasting glucose (4.3, 1.3-27.9, 0.036), reduced HDL-cholesterol (5.2, 1.2-23.6, 0.032) and elevated triglycerides (6.2, 1.4-28.3, 0.019). Factors as age, sex, transaminases, HBV-DNA or genotype were not related with liver fibrosis. The presence of metabolic syndrome has a 69% of positive predictive value and 89% of negative predictive value for significant fibrosis.
Different components of metabolic syndrome are associated with fibrosis development in CHB inactive carriers. In the absence of metabolic syndrome, significant fibrosis is uncommon in this population.
Journal of Gastroenterology and Hepatology 11/2013; · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introducción: Uno de los problemas asociados a la infección por VIH es el desarrollo de neoplasias. La incidencia y espectro de los distintos cánceres se ha visto modificada con la incorporación del tratamiento anti-retroviral de gran actividad (TARGA). El objetivo del presente estudio es describir las características clínicas y epidemiológicas y el pronóstico de pacientes infectados con VIH que han desarrollado una neoplasia. Material y Métodos: Estudio observacional retrospectivo de una cohorte de pacientes con infección por VIH que desarrollaron algún cáncer en el periodo comprendido entre 1993-2010 en un hospital de referencia. Se compararon las variables entre los casos de neoplasias definitorias de SIDA (NDS) y no definitorios de SIDA (NNDS). Resultados: Se identificaron 125 pacientes con al menos una neoplasia. Los cánceres más frecuentes fueron: linfoma no Hodgkin (n: 39; 30,2%), sarcoma de Kaposi (n: 20; 15,5%), enfermedad de Hodgkin (n: 11; 8,8%), neoplasia pulmón (n: 20; 16%) y hepatocarcinoma (n: 9; 6,9 %). La edad media fue 42 ± 11 años, 84% varones, 55,8% estaban co-infectados por VHB y/o VHC. Las conductas de riesgo fueron: 45,6% usuarios de drogas vía parenteral, 16,8% hombres con relaciones sexuales con hombres y 20% heterosexuales. Se encontraron 67 NNDS (52%) y 62 (48%) NDS; los pacientes con NNDS presentaron mayor tiempo de evolución de la infección por VIH y de exposición a TARGA, mayor recuento de CD4 y mejor control virológico que los del grupo de NDS. Desarrollaron un segundo tumor cuatro pacientes. La supervivencia global fue de 34,7%. Conclusiones: Se constata un aumento en la incidencia de NNDS, que se presentan en pacientes con mejor control virológico e in-munológico que los NDS. La mortalidad de los pacientes con infección por VIH y enfermedad tumoral continúa siendo muy elevada.
Revista chilena de infectologia: organo oficial de la Sociedad Chilena de Infectologia 04/2013; 30(2):156-161. · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: The development of malignancies is a problem associated with HIV infection. The incidence and spectrum of malignancies has been modified with the addition of highly active antiretroviral therapy (HAART). Aim: To describe the clinical and epidemiological characteristics and prognosis of HIV patients who have developed a malignancy. Methods: Retrospective observational study was conducted in HIV + patients who developed a malignancy between 1993-2010 in a referral hospital. AIDS-defining malignancies (ADN) and non-AIDS-defining malignancies (NADN) were compared. Results: 125 patients were identified with at least one malignancy. The most frequent malignancies were: non-Hodgkin lymphoma (n; 39; 30.2%), Kaposi's sarcoma (n: 20; 15.5%), Hodgkin's disease (n: 11; 8.8%), lung cancer (n: 20; 15.5%) and hepatocellular carcinoma (n: 9; 6.9 %). The mean age was 42 ± 11 years, 84% male, 55.8% were coinfected with HBV and or HCV. The risk behaviors were: 45.6% intravenous drug users, 16.8% men who have sex with men and 20% heterosexuals). There were 67 (52%) NADN and 62 (48%) ADN; NADN patients had a longer story of HIV infection and longer exposure to HAART, better level of immunodeficiency and better virological control than ADN patients. Four patients developed a second malignancy. Overall survival was 34.7%. Conclusions: We found an increased incidence of NADN, appearing in patients with better virological and immunological control than ADN group. Mortality of patients with HIV infection and malignancy is still very high.
Revista chilena de infectologia: organo oficial de la Sociedad Chilena de Infectologia 04/2013; 30(2):156-61. · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection.
HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 μg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin β (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response.
A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR.
A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.
The Journal of Infectious Diseases 07/2012; 206(6):961-8. · 5.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study assesses the clinical usefulness of the hepatitis C core antigen assay for monitoring of patients being treated for chronic hepatitis C virus (HCV) infection. Eighty-six serum samples were selected at random from 16 patients and levels of HCV RNA and HCV core antigen were determined simultaneously and in parallel to compare both techniques. The data obtained were compared by Pearson's correlation and the coefficients calculated by Fisher transformation and by calculating the difference and standard error. A good linear correlation was observed between both techniques. Maximum correlation, with significant difference, was found between patients infected with the 1a genotype and other genotypes. In conclusion, the HCV core antigen assay is useful for the diagnosis of early infection; however, its use for determining the exact timing of viral elimination during treatment is clearly unsuitable.
Journal of Virological Methods 10/2004; 120(2):173-7. · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acquired trichomegaly of the eyelashes in HIV-infected patients usually appears at the late stage of HIV infection. Eyelash length was measured in a series of 204 HIV patients, and no correlation with CD4 cell count, viral load, Centers for Disease Control and Prevention category, and AIDS case criteria was established. Our data support the finding that eyelash trichomegaly is currently uncommon in HIV-infected patients, perhaps because of antiretroviral therapy or an improvement in their immune situation.
[Show abstract][Hide abstract] ABSTRACT: Treatment of hepatitis C virus (HCV) has become a major challenge in HIV-infected individuals. No data exist on the efficacy and tolerability of pegylated IFN (peg-IFN) plus ribavirin in HIV-co-infected patients.
Subcutaneous peg-IFN (150 microg weekly during the first 12 weeks and 100 microg weekly thereafter) plus ribavirin (400 mg twice a day) was given to 68 HIV-infected patients with chronic hepatitis C, having CD4 cell counts greater than 300 cells/microl, plasma HIV-RNA less than 5000 copies/ml, and elevated aminotransferase levels. All were naive for IFN, and 73% were receiving antiretroviral drugs.
Plasma HCV-RNA levels greater than 800 000 IU/ml were seen in 50%, and 35% carried HCV genotype 3. Adverse events leading to treatment discontinuation occurred in 10 patients (15%). One patient taking didanosine developed pancreatitis. Severe weight loss occurred in 70% of patients. Clearance of HCV-RNA at the end of therapy (6 months for HCV-3 and 12 months for HCV-1/4) occurred in 50% of patients (81% with HCV-3 versus 30% with HCV-1/4). As 30% relapsed, the overall sustained response rate was 35% (28% in the intent-to-treat analysis). The main predictors of response were infection with HCV-3 and low HCV load.
Treatment with peg-IFN and ribavirin is relatively well-tolerated in HIV/HCV-co-infected patients, although new side-effects, including pancreatitis and severe weight loss, may result from the interaction of ribavirin with antiretroviral drugs. Overall, therapy provides cure to one third of patients, a rate significantly lower than that seen in HCV-monoinfected individuals. Given that relapses are common, extended periods of therapy should be investigated.
[Show abstract][Hide abstract] ABSTRACT: The purpose of our study was to assess the presence of nelfinavir (NFV)-associated resistance mutations at the time of early virological failure in subjects receiving NFV as part of a first protease inhibitor (PI)-based triple regimen.
Subjects failing their first PI-based NFV-containing triple regimen were identified in six Spanish hospitals. HIV genotyping was carried out in plasma samples collected at the time of the first viral rebound.
Upon initiation of NFV-based therapy, 19 of the 30 subjects (63%) were naïve; 11 (37%) had been exposed to nucleoside analogues. Median HIV-RNA at the time of viral rebound was 4, 180 copies/ml. PCR-amplified products were obtained in 22 subjects (73%). These products were sequenced and primary PI resistance mutations were recognized in 6 patients (27%). All six individuals harbored the D30N mutation, and none presented the L90M mutation. Other PI resistance mutations were present in 5 subjects (at codons 36, 63, 71, 77, 82 and/or 88). Secondary PI resistance mutations were present in another 9 subjects. By contrast, mutations conferring resistance to reverse transcriptase inhibitors were present in 50% of the patients, and the M184V substitution was the most frequently seen.
Nearly 75% of patients failing their first PI-based triple regimen containing NFV do not harbor PI resistance mutations. The D30N substitution, rather than L90M, is the most frequently recognized, which does not challenge the efficacy of further rescue interventions with other PIs. This observation supports the use of nelfinavir as first protease inhibitor.
Medical science monitor: international medical journal of experimental and clinical research 10/2002; 8(9):CR620-3. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The intramuscular administration of interferon-beta (IFN-beta) at a dosage of 6 million units three times per week for 6 months has been evaluated in 90 patients included in a multicenter, randomized, controlled trial for the treatment of chronic hepatitis C. Transaminase levels were significantly reduced in IFN-beta-treated patients (p = 0.015) and were significantly lower with respect to those of the untreated controls (p = 0.040 at 6 months). Four treated (8%) and one untreated (2.5%) patients had normal transaminase values after 6 months. At study end (12 months), three quarters of the IFN-beta-treated patients had sustained transaminase normalization, whereas the untreated case had relapsed. Hepatitis C viremia was cleared in 6 (12%) treated patients but in none of the untreated controls (p = 0.058). Side effects of IFN-beta were infrequent (a mild flu-like syndrome in < 10%, asthenia in 16%, anorexia in 8%, headaches and weight loss in 8%, and hair loss in 4%). Leukocyte and platelet counts decreased during IFN-beta treatment, but no dose modifications were necessary. Such decreases were not statistically significant when compared with the levels in the untreated controls. Intramuscular IFN-beta at the dosage used has little efficacy in the treatment of chronic hepatitis C. Because of IFN-beta tolerance, higher doses and alternate routes of injection might prove beneficial for the treatment of this disease.
Journal of Interferon & Cytokine Research 01/1997; 17(1):27-30. · 3.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy and safety of recombinant α-interferon (IFN) therapy for chronic hepatitis C (CHC) was assessed in 57 HIV-infected individuals with CD4+ T cells above 200/mm3 and compared to the response obtained in 21 HIV-negative patients with CHC. IFN 5 mega⊎ was given three times a week subcutaneously for 3 months. In responding patients, IFN 3 mega⊎ three times a week was additionally administered for 9 months. After 8 months follow-up in HIV-infected patients, 38% (22/57) achieved normal (complete response, CR) alanine aminotransferase (ALT) values. Partial response (PR) was seen in 21% (12/57), and 40% (23/57) did not respond. Patients with CD4+ cells above 500/mm3 achieved CR in 58% (14/24) of cases compared to 24% (8/33) among those having a lower CD4+ count (P<0.01). Females attained CR in 60% (9/15) of cases, and men in only 30.9% (13/42) (P<0.01). No serious side effects or opportunistic infections were observed during the study period. However, three (5.2%) patients showed a dramatic fall in total CD4+ T cell count after beginning IFN therapy.Among 21 HIV-negative patients, after 8 months follow-up, CR was achieved in 10 (47%), PR in four (19%), and seven (33%) did not respond. We concluded that IFN therapy seems to be well tolerated and useful in HIV-infected patients suffering CHC. The rate of CR was not significantly different compared to that observed in HIV-negative patients (38% vs. 47%), relative risk (RR) = 0.67 (0.19–2.37). However, in HIV-positive patients, a lack of response to IFN therapy was particularly associated with a CD4+ cell count lower than 500/mm3 (only 24% achieved CR) compared to the response obtained in patients with CD4+ count above 500/mm3 (CR was seen in 58%) (P<0.01). The effect of IFN therapy on CD4+ T cells needs to be clarified in these patients.
Journal of Infection 07/1995; 31(1-31):9-13. · 4.02 Impact Factor